bluuebunny/crossref_metadata_2025 huggingface dataset:
Digital dermoscopy in clinical practise: a three‐centre analysis
Authors: Wollina Uwe , Burroni Marco , Torricelli Rocco , Gilardi Stefano , Dell'Eva Giordana , Helm Cathrine , Bardey Wolfgang
Published: February 2007

Background: Early detection of cutaneous melanoma is the most important step to improve prognosis. In recent years objective techniques have been developed to improve diagnostics of pigmented lesions superior to the naked eye. Digital dermoscopy offers several advantages such as independence from the investigator, format ready for teledermatology and image storage, and comparability.

Setting: In a routine setting including three centres in Europe, i.e. Lugano and Locarno in Switzerland, and Dresden in Germany, the usefulness of digital dermoscopy in daily routine has been evaluated.

Patients and methods: Digital dermoscopy was performed with the DB‐MIPS© system in 1308 patients, and 3544 pigmented lesions were evaluated. A total of 466 pigmented lesions were surgically removed and classified by histopathology. Among those 52 melanomas and 299 dysplastic, naevi could be identified. DB‐MIPS© system evaluated 35 variables of geometrics, colour, colour distribution and texture. Lesion identification is realized by clustering. Another important part of the analysis was to study the decision making, i.e. removal or follow‐up of lesions. The tendency to follow‐up was defined as the ratio of (number of suspicious lesions‐removed lesions)/suspicious lesions. The interventism is defined as the ratio of the number of removed lesions to the number of suspicious lesions.

Results: The DB‐MIPS© system was robust and easy in handling in daily routine. The data analysis and digital imaging were realized in real time. Fifty‐two melanomas could be identified including eight in situ melanomas and 33 T1a melanomas (thinner than 1 mm). Sensitivity of digital dermoscopy varied between 90% and 95% between the three centres. Specificity varied between 79.6% and 93.3%. The centres differed in the patient population, the mean diameter of pigmented lesions and decisions. Interventism varied between 36.3% and 76.0%, follow‐up varied from 24% to 63%. Higher levels of clinician's false positive were associated with a higher percentage of interventism.

Conclusions: Digital dermoscopy offers advantages for daily routine in detection of early melanoma. Sensitivity and specificity for early melanomas is high and thereby, the experienced dermatologist can be easily supported in daily routine of a pigment lesion clinic to improve diagnostics and hopefully prognosis in cutaneous melanoma.
Indentometric analysis of in vivo skin and comparison with artificial skin models
Authors: Jachowicz J. , McMullen R. , Prettypaul D.
Published: February 2007

Background/purpose: The mechanical properties of the skin have been previously analyzed by a number of different techniques including torsional analysis, cutometery, gas‐bearing electrodynamometry, etc. The objective of this work is to present quantitative analysis of skin rheology by a technique termed indentometry.

Methods: The instrument used was a texture analyzer, which is a mechanical tensiometer simulating the process of touch. The experiments were carried out on human subjects as well as on artificial skin models. They included indentometry tests performed by using spherical probes with various geometrical dimensions as well as stress relaxation and creep experiments. The experimental data were interpreted by using the Hertz theory of contact mechanics and by calculation of fundamental parameters such as the modulus of elasticity.

Results: The calculated Young's modulae for skin models ranged from 5.5 × 104 to 17.7 × 104 N/m2, while the corresponding values for forearm and facial skin of ten panelists were found to be in the range of 0.7 × 104 –3.3 × 104 N/m2. In addition, stress relaxation and creep experiments were conducted, which permitted the assessment of the viscoelastic properties of skin. The results of these measurements were interpreted within the framework of the Kelvin–Voigt model of delayed elasticity leading to the calculation of viscosities and relaxation times. Indentomeric data, obtained by varying the diameter of the indentor and the indentation depth, are also discussed.

Conclusion: The indentometric analysis for both in vivo skin and artificial skin models could be interpreted by using the Hertz theory of contact mechanics. The loading and unloading indentometric curves could be used to assess the viscoelasticity of the investigated materials while creep and stress relaxation processes were analyzed quantitatively by the Kelvin–Voigt model with one relaxation time.
Altered motor activity, exploration and anxiety in heterozygous neuregulin 1 mutant mice: implications for understanding schizophrenia
Authors: Karl T. , Duffy L. , Scimone A. , Harvey R. P. , Schofield P. R.
Published: February 2007

Human genetic studies have shown that neuregulin 1 (NRG1) is a potential susceptibility gene for schizophrenia. Nrg1 influences various neurodevelopmental processes, which are potentially related to schizophrenia. The neurodevelopmental theory of schizophrenia suggests that interactions between genetic and environmental factors are responsible for biochemical alterations leading to schizophrenia. To investigate these interactions and to match experimental design with the pathophysiology of schizophrenia, we applied a comprehensive behavioural phenotyping strategy for motor activity, exploration and anxiety in a heterozygous Nrg1 transmembrane domain mutant mouse model (Nrg1 HET) using different housing conditions and age groups. We observed a locomotion‐ and exploration‐related hyperactive phenotype in Nrg1 HETs. Increased age had a locomotion‐ and exploration‐inhibiting effect, which was significantly attenuated in mutant mice. Environmental enrichment (EE) had a stimulating influence on locomotion and exploration. The impact of EE was more pronounced in Nrg1 hypomorphs. Our study also showed a moderate task‐specific anxiolytic‐like phenotype for Nrg1 HETs, which was influenced by external factors. The behavioural phenotype detected in heterozygous Nrg1 mutant mice is not specific to schizophrenia per se, but the increased sensitivity of mutant mice to exogenous factors is consistent with the pathophysiology of schizophrenia and the neurodevelopmental theory. Our findings reinforce the importance of carefully controlling experimental designs for external factors and of comprehensive, integrative phenotyping strategies. Thus, Nrg1 HETs may, in combination with other genetic and drug models, help to clarify pathophysiological mechanisms behind schizophrenia.
Short Implants Placed One‐Stage in Maxillae and Mandibles: A Retrospective Clinical Study with 1 to 9 Years of Follow‐Up
Authors: Maló Paulo , De Araújo Nobre Miguel , Rangert Bo
Published: February 2007

Background:  The use of short implants (7–8.5 mm) has historically been associated with lower survival rates than for longer implants. However, recent clinical studies indicate that short implants may support most prosthetic restorations quite adequately, but still clinical documentation is sparse.

Purpose:  The purpose of this study was to report on the placement of short Brånemark implants, testing the hypothesis that short implants in atrophied jaws might give similar long‐term implant survival rates as longer implants used in larger bone volumes.

Materials and Methods:  This retrospective clinical study included 237 consecutively treated patients with 408 short Brånemark implants supporting 151 fixed prostheses. One hundred thirty‐one of the implants were 7‐mm long, and 277 were 8.5‐mm long. Final abutments were delivered at the time of surgery, and final prostheses were delivered 4 to 6 months later.

Results:  One hundred and twenty six of the 7‐mm implants (96%) have passed the 1‐year follow‐up; 110 (84%), the 2‐year follow‐up; and 88 (67%), the 5‐year follow‐up. Five implants failed in four patients before the 6‐month follow‐up, giving a cumulative survival rate of 96.2% at 5 years. The average bone resorption was 1 mm (SD=0.6 mm) after the first year and 1.8 mm (SD=0.8 mm) after the fifth year of function.

Two hundred sixty nine of the 8.5‐mm implants (97%) have passed the 1‐year follow‐up; 220 (79%), the 2‐year follow‐up; and 142 (51%), the 5‐year follow‐up. Eight implants failed in seven patients before the 6‐month follow‐up, giving a cumulative survival rate of 97.1% at 5 years. The average bone resorption was 1.3 mm (SD=0.8 mm) after the first year and 2.2 mm (SD=0.9 mm) after the fifth year of function.

Conclusions:  The cumulative survival rates of 96.2 and 97.1% at 5 years for implants of 7.0‐ and 8.5‐mm length, respectively, indicate that one‐stage short Brånemark implants used in both jaws is a viable concept.
Guided Bone Augmentation around a Titanium Bone‐Anchored Hearing Aid Implant in Canine Calvarium: An Initial Comparison of Two Barrier Membranes
Authors: Sommerlad Susan , Mackenzie Deborah , Johansson Carina , Atwell Rick
Published: February 2007

Background:  The placement of a bone‐anchored hearing aid (BAHA) implant in young children may be hampered by the presence of thin, poor‐quality calvarial bone. The use of extraskeletal guided skull bone augmentation around the titanium implant is one potential solution.

Purpose:  To compare the effectiveness of a collagen membrane BioSISt (Cook Biotech Inc., Lafayette, IN, USA) and a PGA/PLA barrier membrane, Osseoquest (W.L. Gore & Associates, Flagstaff, AZ, USA) in promoting extraskeletal bone formation, when combined with cancellous bone graft, around a titanium implant in the canine calvarium. The quality and quantity of bone tissue was compared.

Materials and Methods:  A 4‐mm titanium BAHA implant was placed in the cranial parietal bone of 11 dogs. The implant protruded from the bone surface by a measured distance. Two groups, each of three dogs, received an implant, cancellous bone graft, and either a BioSISt or Osseoquest membrane. Three dogs received implant and bone graft (positive controls), and two received an implant only (negative controls). Samples were retrieved at 3, 6, and 9 months after placement. Undecalcified histologic and histomorphometric assessments were made of the augmented bone thickness, and bone gain factors were calculated for each sample group.

Results:  The process of osseointegration of the implants was ongoing and increased over time. Bone generation occurred with both test membranes and the early trabecular bone that formed, matured, and remodelled to compact bone at 9 months. BioSISt membrane samples showed superior quality and quantity of augmented bone compared with Osseoquest samples that exhibited thinner bone with persistent inflammation. Quantitatively, the BioSISt samples showed statistically greater new bone contact and bone area than both the positive and negative controls, whereas Osseoquest samples did not. The bone gain factor was statistically greater for BioSiSt samples when compared to the positive and negative controls whereas the Osseoquest samples were not.

Conclusions:  In this study, the collagen BioSISt membrane promoted bone formation of superior quality and quantity compared with the polyglycolic/polylactic acid‐based Osseoquest membrane and positive and negative controls over 9 months. Further investigation of the use of the collagen BioSISt membrane for cranial bone augmentation is warranted.
Strychnine‐Sensitive Glycine Receptors Mediate Analgesia Induced by Emulsified Inhalation Anaesthetics in Thermal Nociception but Not in Chemical Nociception
Authors: Chen Yan , Dai Ti‐jun , Zeng Yin‐ming
Published: February 2007

Abstract:  The present study was designed to investigate the role of strychnine‐sensitive glycine receptors in analgesia induced by emulsified inhalation anaesthetics. After having established the mice model of analgesia by intraperitoneal or subcutaneous injections of appropriate doses of ether, enflurane, isoflurane or sevoflurane, we injected different doses of strychnine intrathecally and then observed the effects on the tail‐flick latency using the tail‐withdrawal test and the writhing times and acetic acid‐induced writhing test. In the tail‐withdrawal test, all four emulsified inhalation anaesthetics (intraperitoneally) significantly increased the tail‐flick latency (P < 0.01) compared with baseline, and the increase of tail‐flick latency induced by four emulsified inhalation anaesthetics can be abolished by intrathecally injected strychnine. In the acetic acid‐induced writhing test, writhing times inhibition induced by subcutaneous administration of four emulsified inhalation anaesthetics was not effected by intrathecal strychnine (0.1, 0.2 and 0.4 µg). The data presented in this study suggest that glycine receptors are specifically involved in mediating the analgesic effect of ether, enflurane, isoflurane and sevoflurane on thermal‐induced nociception but not chemcially induced nociception.
Prolonged Effects of Poly(lactic‐co‐glycolic acid) Microsphere‐Containing Huperzine A on Mouse Memory Dysfunction Induced by Scopolamine
Authors: Wang Chaoyun , Zhang Taiping , Ma Hongmei , Liu Juntian , Fu Fenghua , Liu Ke
Published: February 2007

Abstract:  Huperzine A is an anticholinesterase and cognitive enhancer, which is able to alleviate the symptoms of memory dysfunction in the mouse. The fast metabolization rate and narrow therapeutic spectrum makes it unfit for clinical use. Poly(lactic‐co‐glycolic acid) microsphere as delivery system effectively maintains the blood concentration of huperzine A by a slow‐release effect over a long time. In the present article, we investigated the prolonged protective effect of microsphere‐containing huperzine A on memory dysfunction induced by scopolamine. Spectrophotometric assay was used to determine the activity of acetylcholinesterase (AChE) and passive avoidance tests to evaluate memory performance. The results show that a bolus dose of microsphere‐containing huperzine A (at a dose of 300 µg/kg or 600 µg/kg) administered intramuscularly can effectively maintain drug activity and significantly decrease the activity of AChE from day 3 to 14, the strongest effect seen on day 3 and 7. Accompanying the reduction of the activity of AChE, microsphere‐containing huperzine A (300 µg/kg or 600 µg/kg) remarkably increased transfer latency time and no transfer response on the second trial through mitigating the memory impairments induced by scopolamine as compared to the scopolamine model group. Microsphere‐containing huperzine A showed cognitive enhancing properties and anticholinesterase activity and may thus be a candidate for treatment of memory impairment.
Identification of genetic variations of exon 2 of BoLA‐DQB gene in five Chinese yellow cattle breeds
Authors: Wang K. , Sun D. X. , Zhang Y.
Published: February 2007

One hundred and eighty animals from five Chinese yellow cattle breeds were used to identify genetic variations in the exon 2 of BoLA‐DQB by polymerase chain reaction (PCR) followed by DNA sequencing analysis. A total of 35 alleles of BoLA‐DQB including 19 newly identified ones were found. The number of alleles represents differences in breeds, indicating genetic variations among different breeds. The number of new alleles identified in this study suggests that the number of BoLA‐DQB alleles is greater than what has been reported. The estimation of the average rate of synonymous (dS) and non‐synonymous (dN) substitution in the exon 2 of BoLA‐DQB showed there was a higher ratio of dN to dS substitutions in the peptide‐binding site region, and such differences were significant in all five breeds P < 0.01).
A three‐base‐deletion polymorphism in the upstream non‐coding region of human interleukin 7 (IL‐7) gene could enhance levels of IL‐7 expression
Authors: Song H. , Nakayama E. E. , Likanonsakul S. , Wasi C. , Iwamoto A. , Shioda T.
Published: February 2007

Interleukin 7 (IL‐7) is a key factor in the survival, development and proliferation of B and T lymphocytes. Elevation of plasma IL‐7 has been reported in several lymphopenia cases such as HIV‐1 patients. After patients started to receive antiretroviral drugs and their CD4+ cell counts had recovered, IL‐7 in plasma decreased to normal levels. There are considerable variations in the levels of plasma IL‐7 as well as the rate of CD4+ T‐cell restoration. Although pre‐treatment plasma IL‐7 levels have been shown to be prognostic for the rate of post‐treatment CD4+ T‐cell restoration, the mechanisms responsible for the variations in plasma IL‐7 and rate of CD4+ T‐cell restoration are still completely unknown. In the study here, we searched for genetic polymorphisms that might affect levels of IL‐7 gene expression. For this purpose, we used 1658‐bp PCR‐amplified fragments of the IL‐7 gene containing 1470 bp of the upstream non‐coding region obtained from 151 Japanese and 234 Thai subjects. We found two novel human genetic polymorphisms in the upstream non‐coding region of the IL‐7 gene. The luciferase reporter assay demonstrated that one of those polymorphisms could increase the gene expression of IL‐7. We speculate that this polymorphism, a three base ATC deletion just upstream of an out‐of‐frame ATG codon in the upstream non‐coding region of the IL‐7 gene, reduces the efficiency of translation from the upstream, out‐of‐frame ATG, resulting in increased translation efficiency from the authentic ATG of IL‐7. Although the frequency of this allele is very low, it would be interesting to analyse this polymorphism in HIV‐1‐infected individuals with different rates of immune reconstitution after treatment with a highly active antiretroviral therapy.
National Survey of Hemapheresis Practice in Hungary 2001–2004
Authors: Belák Mihály , Jákó János
Published: February 2007

Abstract:  In the current study, the authors evaluated data provided by Hungarian hemapheresis centers to the National Health Insurance (NHI) organization between 2001 and 2004 with the intention of having costs reimbursed. The primary objective of the present study was to rank data by frequency of indications of therapeutic plasma exchange (TPE). Furthermore, we compared frequency data with the Canadian TPE Registry and reviewed medical evidence regarding the adequacy of applying TPE at chosen indications based on data in literature.

It was concluded that the number of TPEs (and thus the reimbursed costs) increased steadily year by year. It is worth considering the difference between the five most frequent indications of TPE in Hungary or in Canada. Clinicians tend to apply TPE in many cases as a last resort treatment of many diseases unresponsive to conventional therapy. Consequently, there are many illnesses for which the value of TPE is still questionable (or unproven) and its use is considered investigational or experimental. Nevertheless, cumulative medical experience does not always confirm the adequacy of TPE in all treatments, retrospectively. Thus, limited financial resources oblige clinicians to be judicious in providing apheresis services.
Effects of Low Glucose Degradation Products Peritoneal Dialysis Fluid on the Peritoneal Fibrosis and Vascularization in a Chronic Rat Model
Authors: Kim Chan‐Duck , Kwon Hyeog‐Man , Park Sun‐Hee , Oh Eun‐Joo , Kim Mi‐Hyung , Choi Soon‐Youn , Choi Min‐Jeong , Kim In‐San , Park Min‐Sun , Kim Yong‐Jin , Kim Yong‐Lim
Published: February 2007

Abstract:  In the present study, we examined the effects of a new peritoneal dialysis fluid (PDF) with a low level of low glucose degradation products (GDP) on the functional and structural stability of the peritoneal membrane (PM). Male Sprague‐Dawley rats were divided into three groups: group C (n = 8), without dialysate infusion; group P (n = 12), infused with low‐level GDP solution (4.25% Physioneal, pH 7.0–7.4); and group D (n = 12), infused with conventional solution (4.25% Dianeal, pH 5.2, adjusted to pH 7.0). In groups D and P, animals were infused through a permanent catheter with 25 mL of PDF, twice daily for 8 weeks. Lipopolysaccharide was added into the PDF immediately before infusion on days 8, 9 and 10 in the two dialysis groups. When compared with group P, group D showed a higher glucose mass transfer at weeks 6 and 8, D/P urea at week 8, TGF‐β1 at weeks 4 and 8, and VEGF level at week 8. The submesothelial matrix layer of the parietal peritoneum was significantly thickened in group D and the lectin‐stained blood vessels in this layer were well‐visualized in group D compared with group P. There were significantly more peritoneal blood vessels in group D than group P. The transforming growth factor‐β induced gene‐h3 (βig‐h3) and TGF‐β1 levels in the peritoneal effluent correlated with the submesothelial thickness, which correlated with the dialysate‐to‐plasma ratio (D/P) of protein and, inversely, with the rate of glucose transport (D/D0 glucose, where D is glucose concentration in the dialysate and D0 is glucose concentration in the dialysis solution before it is infused into the peritoneal cavity). The present study showed that low‐GDP PDF effectively attenuated the peritoneal vascularization and fibrosis related to conventional solution.
Safety and Tolerability of Long Lasting LDL‐apheresis in Familial Hyperlipoproteinemia
Authors: Bláha Milan , Cermanová Melanie , Bláha Vladimír , Blažek Martin , Malý Jaroslav , Široký Oldřich , Solichová Dagmar , Filip Stanislav , Řeháček Vít
Published: February 2007

Abstract:  The aim of this work is to arbitrate the incidence of side effects and tolerability of long lasting LDL‐apheresis in familial hyperlipoproteinemia. 1200 procedures were performed and the last 463 of them were evaluated. An immunoadsorption method of LDL‐apheresis was used (continuous blood cell separator Cobe Spectra; secondary device: automated adsorption‐desorption ADA, Medicap; absorption columns: Lipopak). As a whole, 6.26% adverse events were found and subsequently resolved by standard symptomatic therapy. Vaso‐vagal reactions (symptoms of neurovegetative lability) were the most common adverse effects, presented as malaise, weakness, slight and short‐term drop in blood pressure or other general signs. They were all well controlled by symptomatic therapy. We conclude that LDL‐apheresis in the hands of experienced personnel is a safe procedure. An acceptable procedure duration limit, balancing the possibility to achieve a targeted cholesterol level while still maintaining an acceptable patient tolerance, was confirmed to be 4 hours.
Prophylactic Dialysis in Elderly Patients Undergoing Coronary Bypass Surgery
Authors: Bingol Hakan , Akay Hakki Tankut , Iyem Hikmet , Bolcal Cengiz , Oz Kursad , Sirin Gokce , Demirkilic Ufuk , Tatar Harun
Published: February 2007

Abstract: Renal dysfunction is associated with markedly increased risk for both mortality and morbidity in patients undergoing coronary artery bypass surgery (CABG), especially in elderly patients. In the current study, we aimed to determine the impact of prophylactic preoperative hemodialysis on operative outcome in patients with mild renal dysfunction. Between March 2002 and May 2005 a total of 64 patients, all of whom were more than 70 years of age and with preoperative creatinine levels greater than 2 mg/dL, underwent primary elective on pump coronary artery bypass surgery. The mean age was 76.3 ± 6.4 (range 70–83). The patients were prospectively allocated into two groups. Group A was the dialysis group (31 patients) and preoperative prophylactic hemodialysis was carried out in all patients. Group B (33 patients) was taken as a control group without preoperative hemodialysis. During the present study, 10 patients died (15.6%) in the hospital. In the postoperative period mean levels of creatinine were found to be decreased in dialysis group. (2.3 ± 0.8 mg/dL vs. 3.4 ± 0.2 mg/,P = 0.037). The incidence of overall morbidity (such as acute renal failure, need of postoperative dialysis, low cardiac output and multiple organ failure) were also found to be decreased in dialysis group. We conclude from the present study that preoperative renal dysfunction and advanced age increase the risk of mortality and morbidity after on‐pump coronary artery bypass surgery. We believe that perioperative prophylactic hemodialysis is an easy and effective method and it decreases both operative mortality and morbidity in elderly patients with renal dysfunction.
A Case Report of a Diabetic Nephropathy Patient With Cirrhotic Ascites Treated by Peritoneal Dialysis
Authors: Nagai Takashi , Imamura Makoto , Kobayashi Daishiro , Mori Masatomo
Published: February 2007

Abstract:  A 64‐year‐old man was admitted because of abdominal fullness, edema and anorexia. He had come to our hospital for treatment of liver cirrhosis and diabetic nephropathy for 1 year. We started diuretics and human albumin intravenous administration. Although the edema disappeared and abdominal fullness improved a little, blood urea nitrogen (BUN) and serum creatinine became elevated, hepatic function deteriorated and he lost his appetite. We consequently started continuous ambulatory peritoneal dialysis (CAPD) in order to control ascites and uremia. Abdominal fullness, appetite and BUN and serum creatinine improved without hepatic function deterioration. It might be important to start CAPD to control ascites although serum creatinine levels might be slightly elevated.
COMPLETE RHEOLOGICAL CHARACTERIZATION OF TIME‐DEPENDENT FOOD PRODUCTS
Authors: TIU C. , BOGER D. V.
Published: February 2007

Rheological data are presented for three mayonnaise samples. The material shows pseudoplastic behaviour, and also exhibits a yield stress and time‐dependent characteristics. Mayonnaise data are used to demonstrate how the time‐dependent behaviour of a food product can be completely characterized using a simplified kinetic and rheological model.
THE TERMINOLOGY OF FOOD TEXTURE
Authors: JOWITT RONALD
Published: February 2007

The current interest in food texture terminology and previous attempts to develop a system of definitions are noted. A systematic and comprehensive glossary of food texture terms is presented as a basis for discussion with the objective of achieving in due course a generally‐agreed terminology.
Introduction: current practice in acid‐related disorders in Asian countries, and workshop background, design and goals
Authors: CHAN F. K. L. , GOLD B. D. , KINOSHITA Y. , CHAN A. O.‐O. , WONG M.‐S. R. , MAKMUN H. D. , OVARLARNPORN B. , VIVATVAKIN B. , LIN J.‐T. , SHEU B.‐S. , CHANG W.‐H.
Published: February 2007

A workshop on acid‐related disorders in paediatric and elderly populations was held in Asia in 2006 to raise awareness that: (i) these particular age groups require special consideration in their disease management; (ii) to clarify what issues need to be addressed in these populations and (iii) to reach a consensus on recommendations for the management of gastro‐oesophageal reflux disease and other acid‐related disorders in children and the elderly.

Of note, acid‐related disorders, particularly gastro‐oesophageal reflux disease in these populations are less well recognized and studied than those in the adult population between the ages of 20 and 60 years.

A distinguished faculty of practicing gastroenterologists and key opinion leaders from several Asian countries and the United States were thus enlisted to address these issues in the workshop.
Review article: update on gastro‐oesophageal reflux disease in children
Authors: GOLD B. D.
Published: February 2007

It is critical for the clinician who cares for children to distinguish between normal physiological gastro‐oesophageal reflux (GER), and signs and symptoms that occur due to the persistent reflux, defined as gastro‐oesophageal reflux disease (GERD).

The underlying natural history of physiological GER in the paediatric population up to about 12 years of age, is quite distinct from normal reflux in adults. Conversely, the underlying pathophysiology of GERD in both age groups is for the most part similar.

Regurgitation symptoms, which peak by 4‐6 months of age, appear to resolve commonly by 12‐18 months of life. However, there is a growing body of evidence that demonstrates that GERD may not be outgrown in a subset of children. In practice, many clinicians include an empiric therapeutic trial of an H2 receptor antagonist (H2RA) or proton pump inhibitor accompanied by symptom resolution for the diagnosis of GERD. GERD‐associated symptoms in the paediatric population range from regurgitation, often accompanied by arching and irritability, to feeding refusal, and/or poor growth to respiratory symptoms such as nocturnal and/or chronic cough. Upper endoscopy with biopsy may be useful in documenting the presence and severity of macroscopic and microscopic mucosal abnormalities, as well as excluding other disorders such as eosinophilic oesophagitis.

Conservative management, particularly useful in mild GERD, consists of positioning during and after feeds, a 2‐ to 4‐week trial of hydrolysate formula, addition of cereal to formula, and smaller, more frequent feeds. Among the current pharmacotherapeutic options available in the United States (US), the prokinetic agent metaclopramide and the acid‐inhibitory agents (H2RAs, proton pump inhibitors) are the most widely prescribed. Numerous clinical investigations in both adults and children demonstrated that the proton pump inhibitors are more effective than the H2RAs in the relief of GERD symptoms and healing of erosive oesophagitis. The safety profile of the proton pump inhibitors in children is excellent with no significant adverse events observed either in the short‐ or long‐term (>5.5 years continuous use). Finally, surgical procedures for GERD may also be indicated in certain circumstances.
Review article: management issues in acid‐related disorders in the elderly
Authors: KINOSHITA Y.
Published: February 2007

The population of Japan is rapidly ageing and this, along with the Westernization of the diet, is expected to increase the prevalence of gastro‐oesophageal reflux disease.

Issues that call for attention by Asian gastroenterologists in the management of gastro‐oesophageal reflux disease in the geriatric population include functional changes associated with ageing, such as a lower sensitivity to acid stimulation or pain leading to more atypical presenting symptoms vs. greater severity of disease, common swallowing problems, polypharmacy, and the slower metabolism of the drugs by the kidney.

The optimal management of acid‐related disorders in the elderly will need to adequately address all these issues.
Review article: building an algorithm for the management of geriatric acid‐related disorders in Asia
Authors: CHAN F. K. L. , KINOSHITA Y.
Published: February 2007

The special needs of the elderly must be considered in the treatment of acid‐related disorders in older patients. Workshop participants discussed the Genval workshop report algorithm as a step toward building a consensus on the management of elderly patients in Asia.

The consensus reached is summarized as follows:

(i) old age alone is an indication for endoscopic investigation of reflux symptoms;

(ii) elderly patients should undergo endoscopy when they present with acid reflux symptoms;

(iii) a biopsy‐based test for Helicobacter pylori should be performed if endoscopy is done, and eradication of H. pylori is warranted as it will reduce the risk of peptic ulcers and may retard the progression of early precancerous gastric lesions;

(iv) it is not recommended to routinely take additional biopsies for histology in patients with H. pylori infection in the absence of any macroscopic suspicious lesions;

(v) patients with reflux disease LA grade B or below should be started on a standard‐dose proton pump inhibitor for 4–8 weeks, and then followed by step‐down to on‐demand therapy;

(vi) patients with LA grade C or above reflux oesophagitis should be initially given standard‐dose proton pump inhibitor therapy for at least 8 weeks and then continue with maintenance proton pump inhibitor therapy.
Clinical practice recommendations for acid‐related disorders or GERD from childhood to old age in Asia: summary of workshop report
Authors: CHAN F. K. L.
Published: February 2007

The workshops developed eight concensus statements for the diagnosis and management of paediatric acid‐related disorders or GERD, and five statements for geriatric acid‐related disorders or GERD, suitable for clinical use in Asia.
Kant's Formula of the End in Itself: Some Recent Debates
Authors: Denis Lara
Published: February 2007

Kant's formula of the end in itself commands that one treat humanity in oneself and in others always as an end and never merely as a means. Interest in, and debate concerning, this formulation of the categorical imperative has been growing among Kantians and ethicists more generally. After an overview of this formulation and Kant's argument for it, this piece outlines several areas of current debate. It then explores some dominant and emerging positions regarding two questions: the identity of the end in itself, and the relation between the end in itself and the value of other things.
Nodule Formation and Desmoplasia in Medulloblastomas—Defining the Nodular/Desmoplastic Variant and Its Biological Behavior
Authors: McManamy Charles S. , Pears Jane , Weston Claire L. , Hanzely Zoltan , Ironside James W. , Taylor Roger E. , Grundy Richard G. , Clifford Steven C. , Ellison David W. ,   on behalf of the Clinical Brain Tumour Group, Children’s Cancer and Leukaemia Group (formerly the UK Children’s Cancer Study Group), UK
Published: February 2007

Among the variants of medulloblastoma in the current WHO classification of nervous system tumors, the desmoplastic variant, which has been reported to constitute 5%–25% of pediatric medulloblastomas, is defined by its nodular collections of neurocytic cells bounded by desmoplastic internodular zones. We have studied the frequency, morphological features and biological behavior of medulloblastomas in two contemporaneous SIOP/UKCCSG trial cohorts of children with medulloblastomas, CNS9102 (n = 315) and CNS9204 (n = 35), focusing on tumors with nodular and desmoplastic phenotypes. In children aged 3–16 years (CNS9102), the nodular/desmoplastic medulloblastoma represented 5% of all tumors, while in infants aged <3 years (CNS9204) this variant represented 57% of medulloblastomas. Using iFISH to detect molecular cytogenetic abnormalities in medulloblastomas with a nodular architecture, we demonstrated distinct genetic profiles in desmoplastic and non‐desmoplastic (classic and anaplastic) tumors; in particular, abnormalities of chromosome 17 occurred in the latter, but not the former. Significantly different outcomes were demonstrated for classic, nodular/desmoplastic and large cell/anaplastic medulloblastomas in both cohorts. In conclusion, the nodular/desmoplastic medulloblastoma appears to have clinical, genetic and biological characteristics that set it apart from other variants of this tumor.
Differential Pi3K‐pathway Activation in Cortical Tubers and Focal Cortical Dysplasias with Balloon Cells
Authors: Schick Volker , Majores Michael , Engels Gudrun , Hartmann Wolfgang , Elger Christian E. , Schramm Johannes , Schoch Susanne , Becker Albert J.
Published: February 2007

Balloon cells of distinct focal cortical dysplasias type IIb (FCDIIb) and giant cells of cortical tubers in tuberous sclerosis (TSC) constitute neuropathological hallmarks and cytological similarities. In TSC, frequent mutations in the TSC1 or TSC2 genes result in mTOR‐signaling activity. Here, we addressed whether Pi3K‐pathway activation differentiates balloon cells from giant cells. We used immunohistochemistry with antibodies against p‐PDK1 (S241), p‐Akt (S473), p‐tuberin (T1462), p‐p70S6K (T389), p‐p70S6K (T229) and phalloidin‐staining to analyze stress fiber formation in balloon cells of FCDIIb (n = 23) compared with cortical tuber giant cells (n = 5) and adjacent normal CNS tissue as control. We have further established an in vitro assay to assess potential phosphorylation between Akt and S6. We observed phosphorylated (p‐)PDK1, p‐Akt, p‐tuberin, and p‐p70‐kDa S6‐kinase (p‐p70S6K; residue T229) in balloon cells, whereas giant cells showed only equivalent levels of p‐tuberin, p‐p70S6K and stress fibers. Furthermore, Pi3K‐cascade activity in balloon cells may reflect pathway “cross‐talk”. An in vitro assay revealed S6, a major target of p70S6K, to increase phosphorylation of Akt. Our data suggest recruitment of different Pi3K‐cascade factors in the molecular pathogenesis of giant cells in cortical tubers vs. balloon cells in FCDIIb and provides new implications for the development of treatment strategies for these cortical malformations.
Effects of monocarboxylic acid‐derived Cl− channel blockers on depolarization‐activated potassium currents in rat ventricular myocytes
Authors: Zhou Shi‐Sheng , Zhang Li‐Bin , Sun Wu‐Ping , Xiao Fu‐Cheng , Zhou Yi‐Ming , Li Ya‐Jie , Li Dong‐Liang
Published: February 2007

The effects of monocarboxylic acid‐derived Cl− channel blockers on cardiac depolarization‐activated K+ currents were investigated. Membrane currents in rat ventricular myocytes were recorded using the whole‐cell configuration of the patch‐clamp technique. 5‐Nitro‐2‐(3‐phenylpropylamino)‐benzoic acid (NPPB) and niflumic acid (NFA) induced an outward current at 0 mV. Both NPPB and NFA failed to induce any current when used intracellularly or after K+ in the bath and pipette solutions was replaced by equimolar Cs+. Voltage pulse protocols revealed that NPPB and NFA enhanced the steady‐state K+ current but inhibited the transient outward K+ current. Genistein, a tyrosine kinase (PTK) inhibitor, inhibited NPPB‐ and NFA‐induced outward current. Another PTK inhibitor, lavendustin A, produced a comparable effect. In contrast, the inactive analogue of genistein, daidzein, was ineffective. Orthovanadate, a tyrosine phosphatase inhibitor, markedly slowed the deactivation of the outward current induced by NPPB and NFA. The protein kinase A (PKA) inhibitor H‐89 inhibited NPPB‐induced outward current at 0 mV. In contrast, the protein kinase C (PKC) inhibitor H‐7 was without significant effect on the action of NPPB. Pretreatment of the myocytes with genistein or H‐89 prevented the enhancing effect of NPPB. Increasing intracellular Cl− from 22 to 132 mm slightly reduced NPPB‐induced outward current at 0 mV. These results demonstrate that the monocarboxylic acid‐derived Cl− channel blockers NPPB and NFA enhance cardiac steady‐state K+ current, and suggest that the enhancing effect of the Cl− channel blockers is mediated by stimulation of PKA and PTK signalling pathways.
Determinants of force rise time during isometric contraction of frog muscle fibres
Authors: Edman K. A. P. , Josephson R. K.
Published: February 2007

Force–velocity (F–V) relationships were determined for single frog muscle fibres during the rise of tetanic contraction. F–V curves obtained using isotonic shortening early in a tetanic contraction were different from those obtained at equivalent times with isovelocity shortening, apparently because changing activation early in the contraction leads, in isovelocity experiments, to changing force and changing series elastic extension. F–V curves obtained with isotonic and with isovelocity shortening are similar if the shortening velocity in the isovelocity trials is corrected for series elastic extension. There is a progressive shift in the scaling of force–velocity curves along the force axis during the course of the tetanic rise, reflecting increasing fibre activation. The time taken for F–V curves to reach the steady‐state position was quite variable, ranging from about 50 ms after the onset of contraction (1–3°C) to well over 100 ms in different fibres. The muscle force at a fixed, moderately high shortening velocity relative to the force at this velocity during the tetanic plateau was taken as a measure of muscle activation. The reference velocity used was 60% of the maximum shortening velocity (Vmax) at the tetanic plateau. The estimated value of the fractional activation at 40 ms after the onset of contraction was used as a measure of the rate of activation. The rate of rise of isometric tension in different fibres was correlated with the rate of fibre activation and with Vmax during the plateau of the tetanus. Together differences in rate of activation and in Vmax accounted for 60–80% of the fibre‐to‐fibre variability in the rate of rise of isometric tension, depending on the measure of the force rise time used. There was not a significant correlation between the rate of fibre activation and Vmax. The steady‐state F–V characteristics and the rate at which these characteristics are achieved early in contraction are seemingly independent. A simulation study based on F–V properties and series compliance in frog muscle fibres indicates that if muscle activation were instantaneous, the time taken for force to rise to 50% of the plateau value would be about 60% shorter than that actually measured from living fibres. Thus about 60% of the force rise time is a consequence of the time course of activation processes and about 40% represents time taken to stretch series compliance by activated contractile material.
Presynaptic GABAA receptors facilitate GABAergic transmission to dopaminergic neurons in the ventral tegmental area of young rats
Authors: Xiao Cheng , Zhou Chunyi , Li Keyong , Ye Jiang‐Hong
Published: February 2007

γ‐Aminobutyric acid A receptor (GABAAR)‐mediated postsynaptic currents (IPSCs) were recorded from dopaminergic neurons of the ventral tegmental area of young rats in acute brain slices and from mechanically dissociated neurons. Low concentrations (0.1–0.3 μm) of muscimol, a selective GABAAR agonist, increased the amplitude, and reduced the paired pulse ratio of evoked IPSCs. Moreover, muscimol increased the frequency but not the amplitude of spontaneous IPSCs (sIPSCs). These data point to a presynaptic locus of muscimol action. It is interesting that 1 μm muscimol caused an inhibition of sIPSCs, which was reversed to potentiation by the GABAB receptor antagonist CGP52432. Isoguvacine, a selective GABAAR agonist that belongs to a different class, mimicked the effects of muscimol on sIPSCs: it increased them at low (≤ 0.5 μm), and decreased them at a higher concentration (1 μm). Hence, the activation of presynaptic GABAARs facilitates GABA release, which is limited by presynaptic GABABRs. Furthermore, facilitation of sIPSCs by muscimol was eliminated in a medium containing tetrodotoxin or cadmium. It is noteworthy that sIPSC frequency was greatly increased by 4,5,6,7‐tetrahydroisoxazolo[5,4‐c]pyridin‐3‐ol(gaboxadol, or THIP), an agonist with preferential effects on extrasynaptic GABAARs containing α4βδ subunits, or by guvacine, a GABA transport blocker, which increases ambient GABA levels. In addition, sIPSC frequency was attenuated by furosemide, a selective antagonist of α6 subunits. Thus, the presynaptic GABAARs may be situated at extrasynaptic sites and may contain α4/6βδ subunits. Given the marked sensitivity of extrasynaptic GABAARs to ambient GABA, alcohols and anaesthetics, these receptors may present a critical site for regulating synaptic function in the developing brain in both physiological and pathological situations.
Endothelin‐1 activates a Ca2+‐permeable cation channel with TRPC3 and TRPC7 properties in rabbit coronary artery myocytes
Authors: Peppiatt‐Wildman C. M. , Albert A. P. , Saleh S. N. , Large W. A.
Published: February 2007

In the present work we used patch pipette techniques to study the properties of a novel Ca2+‐permeable cation channel activated by the potent coronary vasoconstrictor endothelin‐1 (ET‐1) in freshly dispersed rabbit coronary artery myocytes. With cell‐attached recording bath application of 10 nm ET‐1 evoked cation channel currents (Icat) with subconductance states of about 18, 34 and 51 and 68 pS, and a reversal potential of 0 mV. ET‐1 evoked channel activity when extracellular Ca2+ was the charge carrier, illustrating significant Ca2+ permeability. ET‐1‐induced responses were inhibited by the ETA receptor antagonist BQ123 and the phospholipase C (PLC) inhibitor U73122. The diacylglycerol analogue 1‐oleoyl‐2‐acetyl‐sn‐glycerol (OAG) also stimulated Icat, but the protein kinase C (PKC) inhibitor chelerythrine did not inhibit either the OAG‐ or ET‐1‐induced Icat. Inositol 1,4,5‐trisphosphate (IP3) did not activate Icat, but greatly potentiated the response to OAG and this effect was blocked by heparin. Bath application of anti‐TRPC3 and anti‐TRPC7 antibodies to inside‐out patches markedly inhibited ET‐1‐evoked Icat, but antibodies to TRPC1, C4, C5 and C6 had no effect. Immunocytochemical studies demonstrated preferential TRPC7 expression in the plasmalemma, whereas TRPC3 was distributed throughout the myocyte, and moreover co‐localization of TRPC3 and TRPC7 signals was observed at, or close to, the plasma membrane. Flufenamic acid, Gd3+, La3+ and extracellular Ca2+ inhibited Icat with IC50 values of 2.45 μm, 3.8 μm, 7.36 μm and 22 μm, respectively. These results suggest that in rabbit coronary artery myocytes ET‐1 evokes a Ca2+‐permeable non‐selective cation channel with properties similar to TRPC3 and TRPC7, and indicates that these proteins may be important components of this conductance.
Human Neuroblasts Migrate to the Olfactory Bulb via a Lateral Ventricular Extension
Authors: Curtis Maurice A. , Kam Monica , Nannmark Ulf , Anderson Michelle F. , Axell Mathilda Zetterstrom , Wikkelso Carsten , Holtås Stig , van Roon-Mom Willeke M. C. , Björk-Eriksson Thomas , Nordborg Claes , Frisén Jonas , Dragunow Michael , Faull Richard L. M. , Eriksson Peter S.
Published: February 2007

The rostral migratory stream (RMS) is the main pathway by which newly born subventricular zone cells reach the olfactory bulb (OB) in rodents. However, the RMS in the adult human brain has been elusive. We demonstrate the presence of a human RMS, which is unexpectedly organized around a lateral ventricular extension reaching the OB, and illustrate the neuroblasts in it. The RMS ensheathing the lateral olfactory ventricular extension, as seen by magnetic resonance imaging, cell-specific markers, and electron microscopy, contains progenitor cells with migratory characteristics and cells that incorporate 5-bromo-2′-deoxyuridine and become mature neurons in the OB.
The impact of OSHA recordkeeping regulation changes on occupational injury and illness trends in the US: a time-series analysis
Authors: Friedman Lee S , Forst Linda
Published: February 2007

Objectives:The Survey of Occupational Injuries and Illnesses (SOII), based on Occupational Safety and Health Administration (OSHA) logs, indicates that the number of occupational injuries and illnesses in the US has steadily declined by 35.8% between 1992–2003. However, major changes to the OSHA recordkeeping standard occurred in 1995 and 2001. The authors assessed the relation between changes in OSHA recordkeeping regulations and the trend in occupational injuries and illnesses.

Methods:SOII data available from the Bureau of Labor Statistics for years 1992–2003 were collected. The authors assessed time series data using join-point regression models.

Results:Before the first major recordkeeping change in 1995, injuries and illnesses declined annually by 0.5%. In the period 1995–2000 the slope declined by 3.1% annually (95% CI −3.7% to −2.5%), followed by another more precipitous decline occurring in 2001–2003 (−8.3%; 95% CI −10.0% to −6.6%). When stratifying the data, the authors continued to observe significant changes occurring in 1995 and 2001.

Conclusions:The substantial declines in the number of injuries and illnesses correspond directly with changes in OSHA recordkeeping rules. Changes in employment, productivity, OSHA enforcement activity and sampling error do not explain the large decline. Based on the baseline slope (join-point regression analysis, 1992–4), the authors expected a decline of 407 964 injuries and illnesses during the period of follow-up if no intervention occurred; they actually observed a decline of 2.4 million injuries and illnesses of which 2 million or 83% of the decline can be attributed to the change in the OSHA recordkeeping rules.