bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma Levels of Adrenocorticotropic Hormone and Cortisol in People Living in an Environment Below Sea Level (Jordan Valley) during Fasting in the Month of Ramadan
Authors: El-Migdadi Fayig , El-Akawi Zeyad , Abudheese Rola , Bashir Nabil
Published: April 2003

Objectives: To investigate the effects of Ramdan fasting on plasma levels of ACTH and cortisol in athletic students living in the Jordan Valley (JV) and compare them to those living at above sea level in Ramtha City (RC). Methods: Sample collection and measurements were done in November 1998 from non-fasting and in December 1998 from fasting people. Results: ACTH levels in non-fasting subjects in the JV were 36 ± 4 IU/ml compared to 43 ± 3 IU/ml for those in RC. Cortisol levels were 483 ± 76 (JV) and 539 ± 89 nmol/l (RC). Fasting led to an increase in ACTH (49 ± 6 (JV) and 58 ± 5 IU/ml (RC)) and cortisol levels (637 ± 101 (JV) and 805 ± 72 nmol/l (RC)). Conclusion: Fasting increases ACTH and cortisol levels in an altitude-independent fashion.
Plasma Tumor Necrosis Factor-Alpha Levels and Insulin Resistance in Nondiabetic Hypertensive Subjects
Authors: Demirbaş Berrin , Güler Serdar , Çakır Bekir , Çulha Cavit , Aral Yalçın
Published: April 2003

Objectives: Tumor necrosis factor-α (TNF-α) is associated with insulin resistance in certain conditions. However, whether TNF-α is related to insulin resistance in hypertensive subjects is still controversial. The aim of this study was to determine the status of TNF-α and insulin resistance in hypertension. Methods: Newly diagnosed nondiabetic 17 essentially hypertensive (6 men, 11 women) patients, and 11 control healthy subjects (5 men, 6 women) are involved in the study. Body mass index (BMI), insulin, fasting blood glucose, cholesterol, triglyceride, and TNF-α levels were measured. Insulin resistance is assessed according to homeostasis model of assessment (HOMA-IR). Results: Serum insulin (8.4 ± 2.7 vs. 6.1 ± 1.4 mIU/ml; p < 0.01), triglyceride (245.0 ± 39.9 vs. 193.0 ± 22.8 mg/dl; p < 0.01), and TNF-α (4.2 ± 0.7 vs. 3.0 ± 0.6 pg/ml; p < 0.001) levels, and HOMA-IR (2.0 ± 0.8 vs. 1.3 ± 0.3; p < 0.001) were significantly higher in the hypertensive patients compared to the normotensive control group. There were positive correlations between TNF-α levels and body mass index (r = 0.64, p < 0.01), and triglyceride (r = 0.55 p = 0.02) levels in the whole study group. However, there was no correlation of either TNF-α or HOMA-IR. Conclusions: Our data revealed that hypertensive patients have insulin resistance and higher TNF-α levels, but there is no relation between TNF-α levels and insulin resistance.
EEMCO Guidance for the Measurement of Skin Microcirculation
Authors: Berardesca Enzo , Lévêque Jean-Luc , Masson Philippe
Published: April 2003

The blood supply to the skin is provided by a network of arterioles, capillaries and venules organized into a superficial and a deep plexus. The assessment of skin microcirculation is of valuable interest in cosmetology in the quantification of the sun protection factor, skin irritation and efficacy of antiredness treatments. Skin microcirculation can be measured by means of different techniques, based mainly on the quantification of optical and thermal properties of the skin which are modified by the amount of blood perfusion. Relevant and reproducible data can be obtained only through the understanding of the biophysical background of the technique(s) utilized. Standardization of measuring conditions and procedures is particularly required for blood flow assessment. In this paper, the advantages and disadvantages of the main techniques in use are discussed, and optimization of measurements for laser Doppler techniques is described.
Diffusion of E and Z Urocanic Amphiphiles through Skin and Their Insertion in a Membrane Model
Authors: Sirieix-Plénet J. , Ader J.C. , Miquel C. , Mavon A. , Lauth-de Viguerie N.
Published: April 2003

The incorporation of synthetic urocanic amphiphiles into a membrane model is described. A monomolecular film of dipalmitoyl phosphatidylcholine (DPPC) and cholesterol was formed at the air-water interface and used as a model. In parallel, diffusion of these derivatives through the skin was studied using rat skin on flow-through diffusion cells. The flux and the cumulative amount were determined. Although the structure and the composition of the DPPC/cholesterol monolayer differed greatly from multilayers of epidermal lipids, the results obtained in the incorporation and diffusion studies were similar. The structure of the urocanic amphiphiles was very close, but the membranes led to the following flux or insertion classification: Ester E > Ester Z >> Amide E. From the results obtained and for simplicity, the technique of Langmuir monolayers seems to be highly suited to the primary screening of amphiphilic compounds.
Development of an in vivo Animal Model for Skin Penetration in Hairless Rats Assessed by Mass Balance
Authors: Simonsen Lene , Petersen Mads B. , Benfeldt Eva , Serup Jørgen
Published: April 2003

The aim of the study was to develop an in vivo animal model for studies of the penetration of topically applied drugs into the skin of hairless rats. Protective appliances were designed for non-occluded and finite-dose application of topical formulations. The design allowed 2 test sites for each rat and free mobility throughout the test period. By consecutive tape stripping, monitored by measurements of transepidermal water loss and confirmed by histological examination of skin biopsies, 10 tape strippings were found to remove the stratum corneum completely. For assessment of the model, 14C-salicylic acid and 14C-butyl salicylate were topically applied. Rapid and differentiated percutaneous absorption of both compounds were shown by urinary excretion data. For 14C-salicylic acid the amount on the skin surface, in the stratum corneum and in the viable skin was determined. Total mass balance on the applied radioactivity was performed and a recovery of 90 ± 2% was achieved. The radioactivity found in the protective appliances (<10%) was explained by lateral skin diffusion of the model compounds into the dressings.
Pulmonary Mucormycosis in the Setting of Chronic Obstructive Pulmonary Disease
Authors: Spira Avrum , Brecher Stephen , Karlinsky Joel
Published: April 2003

We describe the first case of pulmonary mucormycosis occurring in a patient with chronic obstructive pulmonary disease (COPD) maintained on chronic low dose oral steroids (10 mg/day). The diagnosis was made by direct histopathological examination and culturing of infected tissue obtained by fiberoptic bronchoscopy. Pulmonary mucormycosis is caused by infection with an opportunistic fungus of the order Mucorales and is an acute, rapidly developing and often fulminant process usually occurring in immunocompromised individuals. Risk factors include neutropenia, hematologic malignancies, uncontrolled diabetes mellitus, skin burns and deferoxamine therapy in dialysis patients. This case illustrates the importance of early suspicion of mucormycosis and immediate diagnostic bronchoscopic examination in cases of rapidly progressing pulmonary infiltrates in COPD patients on low doses of corticosteroids.
Psychosocial Adaptation to Short Stature – An Indication for Growth Hormone Therapy?
Authors: Wygold Thorsten
Published: April 2003

Although growth hormone does not clearly improve final height in non-growth-hormone-deficient children with short stature, it leads to a temporary acceleration of growth velocity. It is an ongoing discussion whether this effect supports psychosocial adaptation to short stature and therefore could be an indication for growth hormone treatment in children with short stature without growth hormone deficiency. We have reviewed recent literature concerning psychosocial consequences of short stature. Together with own data we can demonstrate that short people regularly adapt well to their height and have a good self-esteem. On the other hand, we focus on the problem that most studies on this subject suffer from methodical problems. A growth-related questionnaire that evaluates subjective and objective perceptions of being short in patients and peers is not at hand. As a consequence, psychosocial problems due to short stature have not been exactly classified yet and therefore do not represent an indication for growth hormone therapy.
Step Length Variability at Gait Initiation in Elderly Fallers and Non-Fallers, and Young Adults
Authors: Azizah Mbourou Ginette , Lajoie Yves , Teasdale Normand
Published: April 2003

Background: Normal aging is characterized by functional changes in the sensory, neurological and musculoskeletal systems. These changes affect several motor tasks including postural balance and gait. Gait variability has been suggested to be an important predictor of the risk of falling: the age-related increased variability may result of errors in the control of foot placement and/or center of mass displacement. Falls occur most frequently in elderly populations who scored poorly during transfer of quasi-static to dynamic situations, turning and reaching tasks in clinical tests. This suggests that gait initiation, which is a transient phase between standing and walking, could contribute to an increase in variability because, for elderly, muscular synergies associated with gait initiation occur less frequently than for young adults. Objective: To examine if gait initiation and more particularly the variability of the first step length and the duration of the first double support period are more important for elderly fallers than for eldery non-fallers and young adults. Methods: Elderly fallers, elderly non-fallers, and young adults were asked to initiate gait and walk at least 3 strides. Spatio-temporal characteristics of the first step and following strides were collected and across-trials variability analysed. Results: Elderly fallers showed a much smaller first step length and a longer duration of the double support period. The first step length variability of elderly fallers was more than twice greater than that observed for elderly non-fallers. Conclusion: Considering the importance of proper initial foot placement for gait initiation and for stepping recovery responses, the first step length variability observed for the elderly fallers may be an important predictor of postural problems.
Alterations of CMP-NeuAc:Asialofetuin Sialyltransferase Activities in Human Colorectal Adenocarcinoma
Authors: Vázquez-Martín C. , Gil-Martín E. , Fernández-Briera A.
Published: April 2003

It has been reported that surface glycoconjugates in tumour cells have more complex and more heavily sialylated sugar chains in glycoproteins. Here, we analysed CMP-NeuAc:asialofetuin sialyltransferase activities in total cell membranes from colorectal cancer tissue with respect to normal adjacent tissue, finding enhanced sialyltransferase activities. Determination of the kinetic parameters for the donor substrate, CMP-NeuAc, revealed that the apparent Km in tumour tissue was decreased as regards to the normal value. Furthermore, we failed to find any correlation between this activity and the characteristics of the samples such as the age or sex of the patient, or Dukes’ stage of the tumour. In order to know which sialyltransferase activity was altered, we studied the incorporation of NeuAc into N- and O-linked chains from asialofetuin. The results allow us to conclude that it is on N-linked chains where the activity is enhanced. With respect to α(2,3)- and α(2,6)-NeuAc linkages, we observed that enhanced activity in tumour tissues affects both linkages equally.
Formulation, Development and Characterization of Sustained Release Varnishes Containing Amine and Stannous Fluorides
Authors: Steinberg D. , Rozen R. , Klausner E.A. , Zachs B. , Friedman M.
Published: April 2003

This study describes properties of potential sustained release varnishes (SRV) containing amine fluoride or amine fluoride with stannous fluoride. The release kinetics, antibacterial properties and antiadhesion properties of two potential varnishes were tested. The varnish of ethylcellulose matrix was found to release fluoride for 4 h in vitro, while the formulation based on hydroxypropylmethylcellulose acetate succinate had a rapid release rate. Hydroxyapatite tablets coated with ethylcellulose-based SRV increased adhesion of Streptococcus mutans, while tablets coated with hydroxypropylmethylcellulose acetate succinate-based SRV decreased bacterial adhesion. Both types of SRV demonstrated a strong antibacterial effect on bacteria in biofilm.
Influence of Fluoridated Salt on Urinary Fluoride Excretion of Adults
Authors: Schulte Andreas Gerhard , Gräber Ralf , Kasperk Christian , Koch Martin Jean , Staehle Hans Jörg
Published: April 2003

After the introduction of fluoridated table salt in the staff cafeteria (VZM) of the Heidelberg University Medical and Dental School, the opportunity was taken to determine urinary fluoride excretion of those eating their main daily meals there. Subjects collected 24-hour urine in three fractions (mornings, afternoons, evenings/nights) before fluoridated table salt was introduced in the VZM, and at 6, 12 and 24 months afterwards. The fluoride concentration in the urine was determined. After 24 months, 127 of the original 200 test persons (study group) and 33 of the 60 persons in the control group could be examined. During this period, each participant in the study group took an average of 3.1 of the main meals each week at noon in the VZM. After fluoridated table salt was introduced at the VZM, fluoride excretion increased only in the afternoon urine of the test group; in this respect, the baseline examination disclosed an average of 33.98 ± 21.18 µg/h, while the follow-up examinations revealed averages of between 39.72 ± 22.58 and 42.44 ± 26.16 µg/h. This difference was statistically significant (Kruskal-Wallis test, p < 0.05). It is recommended that in studies of similar questions, fractions of urine should be collected over 24-hour periods.
Dental Caries and Developmental Defects of Enamel in Relation to Fluoride Levels in Drinking Water in an Arid Area of Sri Lanka
Authors: Ekanayake L. , van der Hoek W.
Published: April 2003

The study was conducted to assess caries and developmental defects of enamel in relation to fluoride levels in drinking water and the association between caries experience and the severity of diffuse opacities in children living in Uda Walawe, an area with varying concentrations of fluoride in drinking water in Sri Lanka. A total of 518 14-year-old children who were lifelong residents in this area were examined for dental caries and developmental defects of enamel. But the present analysis is confined to 486 children from whom drinking water samples were collected. The prevalence of enamel defects and diffuse opacities ranged from 27 to 57% while the prevalence of caries ranged from 18 to 29% in the different fluoride exposure groups. The prevalence of enamel defects increased significantly with the increase in the fluoride level in drinking water. Both the caries prevalence and the mean caries experience were significantly higher in children with diffuse opacities than in those without in the group consuming water containing >0.70 mg/l of fluoride. The association between dental caries and the severity of diffuse opacities was also significant only in this group. Children with the mildest form of opacities (DDE scores 3 and 4) had the lowest DMFS (0.25 ± 0.7), and the highest DMFS (1.1 ± 1.7) was found in those with the most severe form of opacities (DDE score 6). In conclusion, the relationship that was observed in this study between fluoride levels in drinking water, diffuse opacities and caries suggests that the appropriate level of fluoride in drinking water for arid areas of Sri Lanka is around 0.3 mg/l. Also individuals with severe forms of enamel defects in high-fluoride areas are susceptible to dental caries.
Generation and characterization of a 12,000-rad radiation hybrid panel for fine mapping in pig
Authors: Yerle M. , Pinton P. , Delcros C. , Arnal N. , Milan D. , Robic A.
Published: April 2003

We have constructed a 12,000-rad porcine whole-genome radiation hybrid panel to complement the first generation 7,000-rad panel (IMpRH) and allow higher resolution mapping studies both in specific areas of interest and on the whole genome. We analyzed 243 hybrid clones on the basis of their marker retention frequency to produce a final panel of 90 hybrid clones with an average retention frequency of 35.4%. The resolution of this 12,000-rad panel (IMNpRH2) was compared to the resolution of the 7,000-rad panel (IMpRH) by constructing framework maps in the 2.4-Mb region of porcine chromosome 15 containing the acid meat RN gene. In this region, two-point analysis was used to estimate RH distances and demonstrates their reliability with the estimation of physical distances. This study demonstrates that the 12,000-rad panel constitutes a powerful tool for constructing high-resolution maps. Indeed, the resolution of IMNpRH2 (12–14 kb/cR12,000) is two to three times more than that of IMpRH (35–37 kb/cR7,000). As expected, the increase in the radiation dose allows an increase of the mapping resolution in terms of kb/cR with the same suppleness of use for mapping experiments. In addition the RH map constructed in the region investigated proved to be more homogeneous on IMNpRH2 than on IMpRH.
Proestrous Surge of Gonadotropin-Releasing Hormone Secretion Inhibits Apoptosis of Anterior Pituitary Cells in Cycling Female Rats
Authors: Yin Ping , Arita Jun
Published: April 2003

Estrogen affects apoptotic cell death in estrogen-responsive tissues. The purpose of the present study was to examine dynamic changes in apoptotic cell death in the anterior pituitary gland during the estrous cycle and to investigate neuroendocrine regulation of these changes in cycling female rats. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) for in situ detection of DNA strand breaks revealed that the number of TUNEL-positive anterior pituitary cells was changing during the estrous cycle, with a maximum in the morning of proestrus and a minimum in the morning of estrus. A similar pattern was observed with Bax immunostaining; however, no difference was observed in Bcl-2 immunostaining. Most of Bax-immunoreactive cells were identified as a subpopulation of gonadotropes. Pentobarbital administered in the afternoon of proestrus attenuated the decrease in TUNEL-positive or Bax-immunoreactive cells in the morning of estrus, although estradiol treatment failed to affect it. This action of pentobarbital was reduced by simultaneous treatment with an ovulation-inducing dose of gonadotropin-releasing hormone (GnRH), but not with progesterone, an ovarian steroid also released after GnRH treatment. These results suggest that anterior pituitary cells, mostly gonadotropes, undergo a cyclic change in apoptotic cell death during the estrous cycle and that the inhibition of apoptosis on estrus is due, at least in part, to the proestrous surge of GnRH secretion.
The Hypothalamic Mechanisms of the Hypophysiotropic Action of Ghrelin
Authors: Wren Alison M. , Small Caroline J. , Fribbens Charlotte V. , Neary Nicola M. , Ward Helen L. , Seal Leighton J. , Ghatei Mohammad A. , Bloom Stephen R.
Published: April 2003

Ghrelin is an endogenous ligand for the growth hormone secretagogue (GHS) receptor, expressed in the hypothalamus and pituitary. Ghrelin, like synthetic GHSs, stimulates food intake and growth hormone (GH) release following systemic or intracerebroventricular administration. In addition to GH stimulation, ghrelin and synthetic GHSs are reported to stimulate the hypothalamo-pituitary-adrenal (HPA) axis in vivo. The aims of this study were to elucidate the hypothalamic mechanisms of the hypophysiotropic actions of ghrelin in vitro and to assess the relative contribution of hypothalamic and systemic actions of ghrelin on the HPA axis in vivo. Ghrelin (100 and 1,000 nM) stimulated significant release of GH-releasing hormone (GHRH) from hypothalamic explants (100 nM: 39.4 ± 8.3 vs. basal 18.3 ± 3.5 fmol/explant, n = 49, p < 0.05) but did not affect either basal or 28 mM KCl-stimulated somatostatin release. Ghrelin (10, 100 and 1,000 nM) stimulated the release of both corticotropin-releasing hormone (CRH) (100 nM: 6.0 ± 0.8 vs. basal 4.2 ± 0.5 pmol/explant, n = 49, p < 0.05) and arginine vasopressin (AVP) (100 nM: 49.2 ± 5.9 vs. basal 35.0 ± 3.3 fmol/explant, n = 48, p < 0.05), whilst ghrelin (100 and 1,000 nM) also stimulated the release of neuropeptide Y (NPY) (100 nM: 111.4 ± 25.0 vs. basal 54.4 ± 9.0 fmol/explant, n = 26, p < 0.05) from hypothalamic explants in vitro. The HPA axis was stimulated in vivo following acute intracerebroventricular administration of ghrelin 2 nmol [adrenocorticotropic hormone (ACTH) 38.2 ± 3.9 vs. saline 18.2 ± 2.0 pg/ml, p < 0.01; corticosterone 310.1 ± 32.8 ng/ml vs. saline 167.4 ± 40.7 ng/ml, p < 0.05], but not following intraperitoneal administration of ghrelin 30 nmol, suggesting a hypothalamic site of action. These data suggest that the mechanisms of GH and ACTH regulation by ghrelin may include hypothalamic release of GHRH, CRH, AVP and NPY.
Abnormal Vitamin D Metabolism and Loss of Bone Mass after Renal Transplantation
Authors: de Sévaux Ruud G.L. , Hoitsma Andries J. , van Hoof Harry J.C. , Corstens Frans J.M. , Wetzels Jack F.M.
Published: April 2003

Background/Aim: Osteoporosis is a major complication after renal transplantation. The most important causative factor is the use of corticosteroids, but abnormalities in vitamin D metabolism and persisting hyperparathyroidism could also be involved. The present study examines changes in vitamin D metabolites, intact parathyroid hormone, and bone mineral density (BMD) during the first 2 years after renal transplantation. Methods: Sixty-one patients (38 male, 23 female; age 42 ± 13 years) who received a renal transplant participated in the study. Immunosuppressive treatment consisted of ciclosporin and prednisone. Laboratory parameters and BMD (lumbar spine and hip) were measured at baseline and 1 (laboratory only), 3, 6, 12, and 24 months after transplantation. Results: At the time of transplantation, the 1,25-dihydroxyvitamin D levels were low in all patients. Although we observed a gradual increase, subnormal values were still present in 39 (64%) and 29 (47%) patients 3 and 6 months after transplantation, respectively. From 3 months after transplantation the 1,25-dihydroxyvitamin D level correlated with the creatinine clearance. After transplantation, the intact parathyroid hormone levels declined rapidly to values slightly above normal. The lumbar BMD was nearly normal at the time of transplantation, but decreased rapidly within 6 months (–6.5 ± 4.5%; p < 0.001). A smaller decrease occurred in the femoral neck (–4.1 ± 6.5%; p < 0.001), in Ward’s triangle (–2.4 ± 13.0%; p < 0.01), and in the trochanter (–5.1 ± 6.3%; p < 0.001). After 6 months, the bone mass stabilized. Conclusions: The vitamin D metabolism remains disturbed for a considerable time after renal transplantation. In nearly half of the patients, the levels of active vitamin D remain abnormal for at least 6 months. The BMD decreased during the first 6 months after transplantation and remained stable thereafter. We speculate that the observed abnormalities in vitamin D metabolism may contribute to the early bone loss after renal transplantation.
A Randomized Prospective Trial to Assess the Role of Saline Hydration on the Development of Contrast Nephrotoxicity
Authors: Trivedi Hariprasad S. , Moore Harold , Nasr Samer , Aggarwal Kul , Agrawal Alok , Goel Punit , Hewett John
Published: April 2003

Though simple and attractive, the role of hydration for the prophylaxis of contrast nephrotoxicity has not been definitively established. We prospectively evaluated the role of deliberate saline hydration in patients undergoing nonemergency cardiac catheterization. Patients (n = 53) were randomized on the day prior to scheduled catheterization to one of two groups – group 1 (n = 27) received normal saline for 24 h (at a rate of 1 ml/kg/h) beginning 12 h prior to scheduled catheterization, and group 2 (n = 26) were allowed unrestricted oral fluids. Serum creatinine measured 24 and 48 h postcardiac catheterization was compared to the pre-randomization baseline value. The mean baseline calculated creatinine clearance was 79.6 ± 31.9 ml/min and the mean baseline creatinine was 106 ± 28 µmol/l. An increase in serum creatinine by at least 44.2 µmol/l (0.5 mg/dl), within 48 h of contrast exposure, was considered to represent clinically significant acute renal insufficiency. Ten subjects (18.9%) developed acute renal insufficiency. The incidence of acute renal insufficiency was significantly lower in group 1 (1 out of 27) as compared to group 2 (9 out of 26; p = 0.005 for comparison between groups; relative risk 0.11, 95% confidence interval 0.015 to 0.79). Twenty-four hours after contrast exposure, the mean increase in creatinine was less in group 1 vs. group 2 (8 ± 11 vs. 20 ± 21 µmol/l, p = 0.02). The increase in creatinine was not significantly different in group 1 vs. group 2 48 h after contrast exposure (12 ± 21 vs. 29 ± 40 µmol/l, p = 0.17). Deliberate saline hydration decreases the incidence of contrast-related acute renal failure and the severity of contrast-induced renal dysfunction in patients undergoing non-emergency cardiac catheterization.
Renal Alpha-Actinin-4: Purification and Puromycin Aminonucleoside-Binding Property
Authors: Goto Hiroyuki , Wakui Hideki , Komatsuda Atsushi , Ohtani Hiroshi , Imai Hirokazu , Sawada Ken-ichi , Kobayashi Ryoji
Published: April 2003

Mutations in the gene encoding nonmuscle alpha-actinin-4 (actinin-4), an actin cross-linking protein, lead to congenital nephrosis. This suggests that actinin-4 is an essential component of the glomerular filtration barrier. In the present study, we attempted to purify actinin-4 from the mammalian kidney. We also examined an interaction of the protein with puromycin aminonucleoside (PAN), which can induce nephrosis in animals. A 100-kD protein reactive with antibody against muscle alpha-actinin was purified from the Triton-insoluble cytoskeleton of porcine kidney, by MgCl2 treatment, ammonium sulfate fractionation, and subsequent DEAE-cellulose chromatography and hydroxyapatite chromatography. Its partial amino acid sequence was then determined. A filamentous actin (F-actin)-binding activity of the purified protein was examined by a cosedimentation assay. Interactions of the purified protein and its fragments with PAN were analyzed by an affinity assay using PAN-Sepharose. Determined 134 amino acid sequences of the purified porcine renal 100-kD protein were completely identical with those deduced from nucleotide sequence of the cDNA encoding human actinin-4. The purified protein possessed the known function of alpha-actinin, the F-actin-binding activity, and was tightly bound to PAN. The PAN-binding site was mapped within a central rod domain of the protein, which is a possible interaction site for various cytoskeletal and transmembrane proteins. We have established an efficient purification method for renal actinin-4. Moreover, our findings indicate that the central rod domain of actinin-4 has a high affinity to PAN. In the PAN nephrosis animal model, actinin-4 might be a target protein from PAN nephrotoxicity.
Patterns of Clinically Detectable Treatment Effects with Galantamine: A Qualitative Analysis
Authors: Joffres Christine , Bucks Romola S. , Haworth Judy , Wilcock Gordon K. , Rockwood Kenneth
Published: April 2003

The Clinician’s Interview Based Impression of Change, plus carer interview (CIBIC-Plus) is widely used in anti-dementia drug trials. It includes clinicians’ notes about patients’ behaviour, function, and cognition, and a 7-point clinical global impression of change scale that summarizes patients’ changes during treatment. We analyzed the narrative content of clinicians’ notes from a randomized, controlled trial of galantamine, an anti-Alzheimer’s disease drug, and identified varying degrees of improvement and decline. In general, while most patients were rated as showing ‘no change’, considerable changes were seen in such patients, but were judged by clinicians to have been offset by decline in other areas. Most patients rated as ‘improved’ showed combinations of cognitive, functional and/or behavioural improvement or stability. While patients with signs of cognitive improvement could be found across the scale from ‘very much improved’ to ‘minimally worse’, patients with functional improvement were rated as having improved or not having changed. Cognitive declines in several domains or any cognitive decline seen with functional declines were the chief drivers of worsening ratings. The CIBIC-Plus notes have potential value in identifying reproducible patterns of clinically relevant treatment effects provided that data are consistent and specific, and that seemingly contradictory information is carefully explored. Clinicians appear to be skeptical of cognitive changes not supported by like changes in function or behaviour.
NAD(P)H:Quinone Reductase Activity in Human Epidermal Keratinocytes and Reconstructed Epidermal Models
Authors: Harris Ian R. , Siefken Wilfried , Beck-Oldach Konstanze , Wittern Klaus-Peter , Pollet Dieter
Published: April 2003

Reconstructed epidermal models may provide a suitable and relevant model for screening compounds such as quinones, which affect the activities of phase I and II enzymes involved in epidermal detoxification. Reconstructed epidermis may also allow the study of the metabolism of topically applied compounds by the phase I and II enzymes. We demonstrate that NAD(P)H:quinone reductase (NQR) activity is present in three different types of reconstructed epidermal models and that levels vary depending on the type of model. We also determined the inter- and intrabatch variability and demonstrate that NQR activity can be significantly inhibited by dicumarol treatment. The NQR activity in reconstructed epidermis is similar to that in human epidermis and lower than in cultured keratinocytes. Therefore reconstructed epidermis is a more suitable model for testing the effects of topically applied compounds on NQR activity or the metabolism of the compound by NQR.
The Use of Standardized Human Skin Models for Cutaneous Pharmacotoxicology Studies
Authors: Roguet R.
Published: April 2003

//8RReconstructed skin and epidermis models are finding increasingly numerous applications in cosmetology and dermatology. In particular, they are currently employed to assess the tolerability and efficacy of raw materials and formulations, in conditions approaching those of normal use. Importantly, the use of such models greatly reduces the need for animal testing. Various models of reconstructed skin and epidermis have been developed [1–4] and some are now produced industrially [5–8]. They are used for the prediction of cutaneous irritancy and, to a lesser extent, percutaneous absorption and cutaneous metabolism. However, before being officially recognized as valid alternative methods and entering routine use, standard protocols must be developed to assess their reproducibility and performance as compared with in situ human studies.
Characterization of Reconstructed Skin Models
Authors: Ponec Maria , Boelsma Esther , Gibbs Susan , Mommaas Mieke
Published: April 2003

The aim of the present study was to evaluate tissue architecture and lipid composition of commercially available reconstructed human skin models; EpiDerm™, SkinEthic™ and Episkin™ in comparison to in-house reconstructed epidermis on a de-epidermized dermis (RE-DED) model and native tissue. For this purpose, the tissue architecture was examined using light microscopy, electron microscopy and immunohistochemistry; epidermal lipid composition was analyzed by HPTLC. Histological examination showed a completely stratified epithelium in all skin models closely resembling normal human epidermis. Low intra-batch variation in tissue architecture was observed in all skin models, but moderate to considerable inter-batch variation was noticed. In the stratum corneum extracellular space, lipid lamellae consisting of multiple alternating electron-dense and electron-lucent bands were present. Lipid analyses revealed the presence of all major epidermal lipid classes. Compared with native epidermis and RE-DED in EpiDerm, SkinEthic and Episkin models, the content of polar ceramides 5 and 6 was lower, ceramide 7 was absent, and the content of free fatty acids was very low. Evaluation of the expression and localization of a number of differentiation-specific protein markers revealed that all skin models showed an aberrant expression of keratin 6, skin-derived antileukoproteinase, small-proline-rich proteins, involucrin and transglutaminase. Although variation within batches was low, in particular keratin 6, involucrin and skin-derived antileukoproteinase expression demonstrated some inter-batch variation. In conclusion, all skin models provide a promising means for studying the effects of topically applied chemicals, although the observed deviations in tissue homeostasis and barrier properties need to be diminished. All skin models tested reproduced many of the characteristics of normal human epidermis and therefore provide a morphologically relevant in vitro means to assess skin irritation and perform other skin-related studies.
Risk Factors for Neonatal Mortality in Low-Income Population Subgroups in Karachi, Pakistan
Authors: Hussain R.
Published: April 2003

This paper assesses the risk factors for neonatal mortality (0–28 days of life) for full-term singleton live births. The study sample comprised 1,011 ever-married women who were residents of four multi-ethnic, multi-religious low-income areas of Karachi, Pakistan during 1995. The analysis sample was restricted to 4,488 live births to 912 women. Results showed that 4.8% (n = 217) of all births ended in death in the neonatal period, and 76% (n = 164) of these neonatal deaths occurred in the first week of life. While neonatal mortality rates had declined appreciably over time, a large proportion of neonatal deaths were clustered in a small group of women. The univariate analysis showed a statistically significant association between a number of maternal-level parameters (e.g., mother’s age at birth, level of formal education, employment status, religious affiliation, and consanguinity) and child-level parameters (e.g., birth order, birth interval, survival status of the preceding child, sex of the neonate, year of death). At the multivariate level, consanguinity, birth order and year of death were found to be statistically significant risk factors for neonatal mortality analyses despite adjustment for death clustering. The study highlights the importance of inbreeding as a determinant of early offspring death, and points to the need for better understanding of why deaths are clustered in certain families. Given the widespread practice of close cousin marriages in Pakistan across all socio-economic groups, there is a need to validate the findings in less economically disadvantaged population subgroups within the country.
Pilot Study of Early Diagnosis of Hereditary Haemochromatosis through Systematic Case Finding in Primary Care
Authors: Emery Jon , Rose Peter , Harcourt Jean , Livesey Karen , Merryweather-Clarke Alison , Pointon Jennifer J. , Robson Kathryn
Published: April 2003

Objectives: To test the feasibility of adopting and evaluating a systematic case-finding approach to the early diagnosis of hereditary haemochromatosis (HHC) in primary care, and to estimate the prevalence of presenting conditions for which HHC testing could be offered. Methods: Systematic identification of, and genotyping for, C282Y and H63D mutations in patients presenting in primary care with possible symptoms of HHC during a 4-week period to 1 of 14 doctors in Oxfordshire. Results: From a total of 4,022 consultations, 169 (4.2%; 95% CI: 3.6–4.8) adult patients had possible symptoms of HHC. Of these, 88 (2.2%; 95% CI: 1.7–2.6) were aged 25–70 and were offered genotyping for HHC, of whom 60 agreed to be tested. There were no C282Y homozygotes (0%; 95% CI: 0–6.0), no C282Y/H63D compound heterozygotes (0%; 95% CI: 0–6.0), 2 H63D homozygotes with normal iron indices (3.3%%; 95% CI: 0.4–11.5) and 3 C282Y heterozygotes (5.0%; 95% CI: 1.0–13.9). Conclusions: This study raises doubts about a case-finding approach to early diagnosis of HHC in primary care. The non-specific nature and high prevalence of possible symptoms of HHC in primary care mean that many patients would require testing to identify a single case. Whether this offers a more cost-effective alternative to population screening requires further study.
Ethnic Differences in the Frequency of Prostate Cancer Susceptibility Alleles at SRD5A2 and CYP3A4
Authors: Zeigler-Johnson C.M. , Walker A.H. , Mancke B. , Spangler E. , Jalloh M. , McBride S. , Deitz A. , Malkowicz S.B. , Ofori-Adjei D. , Gueye S.M. , Rebbeck T.R.
Published: April 2003

Objectives: Ethnic differences in prostate cancer incidence are well documented, with African-Americans having among the highest rates in the world. Ethnic differences in genotypes for genes associated with androgen metabolism including SRD5A2 and CYP3A4 also may exist. The aim of this study was to evaluate differences in these genotypes by ethnicity. Methods: We studied cancer-free controls representative of four groups: 147 African Americans, 410 Caucasian-Americans, 129 Ghanaians, and 178 Senegalese. PCR-based genotype analysis was undertaken to identify two alleles (V89L, A49T) at SRD5A2 and *1B allele at CYP3A4. Results: Differences were observed for V89L (variant frequency of 30% in Caucasians, 27% in African Americans, 19% in Ghanaians, and 18% in Senegalese, p = 0.002) and were observed for CYP3A4*1B (variant frequencies of 8% in Caucasians, 59% in African Americans, 81% in Ghanaians, and 78% in Senegalese, p = 0.0001). Pooled data combining the present data and previously published data from from Asian, Hispanic, and Arab cancer-free controls showed significant ethnic differences for SRD5A2 and CYP3A4 polymorphisms. Overall, Asians were least likely to have alleles associated with increased prostate cancer risk, while Africans were most likely to have those alleles. Conclusions: These results suggest that ethnicity-specific differences in genotype frequencies exist for SRD5A2 and CYP3A4. Africans and African-Americans have the highest frequency of those alleles that have previously been associated with increased prostate cancer risk. Future studies should address whether allele frequency differences in part explain differences in prostate cancer incidence in these populations.
Current Status of Stereotactic Biopsy
Authors: Rajshekhar V.
Published: April 2003

The safety and efficacy of CT guided stereotactic biopsy (STB) has been established in several reports published since the early 1980s. Presently, STB is used for the diagnosis of intrinsic brain masses which are judged to be unsuitable for radical excision because of their location, histology or number. It can be combined with adjuvant therapy as the initial treatment of both low and high grade gliomas. It is ideal in determining the histology of focal brain stem masses in children and all brain stem masses in adults. It is the technique of choice in the management of certain lesions such as pineal region germinomas, primary cerebral lymphomas, AIDS related brain masses and deep-seated and eloquent region inflammatory masses. Stereotactic biopsy is, thus, an important tool in the neurosurgeon’s armamentarium.
Clinical Experiences in Neuronavigation
Authors: Chen Han-Jung
Published: April 2003

We have successfully used a navigation system in more than 120 neurosurgical operations for past two years. The neuronavigation system provides high levels of mechanical accuracy in surgical localization, especially for small deep-seated masses or epileptic foci, surgical planning for intrinsic and extrinsic brain tumors, and arteriovenous malformation and guidance of instrumentation of spinal surgery. The ages of the patients were from 12 months to 75 years. The sex distribution was equal. Computed tomography or magnetic resonance imaging with 2–3 mm thick slices were employed for image guidance. The clinical experiences included 50 cases of deep-seated mass, 50 cases of surgical planning for tumor or vascular mass excision and 20 cases of spinal instrumentation treatment. There were no mechanical failures. Neuronavigation definitely provides a good technology in frameless brain and spinal surgeries.
Intra-Operative Image Updating
Authors: Roberts D.W. , Lunn K. , Sun H. , Hartov A. , Miga M. , Kennedy F. , Paulsen K.
Published: April 2003

Intraoperative brain shift and deformation pose challenges for image-guided surgery. One strategy to address these problems utilizes computational modeling coupled with intraoperatively acquired information from efficient and economical sources such as ultrasound and the optics of the operating microscope. Calibration algorithms for the accurate integration of these sparse data sources have been implemented. Assessment has been performed in both phantom and pig brain models, and accuracy better than 2 mm has been achieved. Methods of incorporating these data into the computational model are being developed.
Intraoperative MRI and Adjuvant Radiosurgery
Authors: Schulder Michael , Jacobs Alexander , Carmel Peter W.
Published: April 2003

Introduction: For many patients with brain tumors, the ideal management strategy may be a planned subtotal resection followed by stereotactic radiosurgery (SRS). However, intraoperative visual inspection may be an inadequate measure of the amount of residual lesion. Intraoperative MRI (IMRI) may help to ensure that the goals of surgery have been achieved and that the best possible target for SRS remains. Patients and Methods: We have operated on 68 patients using the PoleStar N-10 IMRI system (Odin Medical Technologies, Yokne’am, Israel). Benign extraaxial lesions were present in 34 patients. In 12 patients subtotal resection and adjuvant SRS were planned. Diagnoses included 5 pituitary adenomas, 4 meningiomas, 2 vestibular schwannomas, and 1 trigeminal schwannoma. Tumor resection was performed until critical structures (e.g. superior sagittal sinus) were being approached and IMRI demonstrated that the lesion was as small as possible. Results: In 1 patient a surgical resection was completed, while in 11 others the plan for subtotal resection was carried out. One patient with an extensive meningioma was treated with fractionated 3-dimensional conformal fractionated radiation therapy, as her tumor remained too large for SRS. In the remaining 10 patients an ideally small target remained for SRS; 3 patients have been treated so far. Conclusions: Adjuvant SRS after subtotal tumor resection is an excellent management strategy for many patients with intracranial tumors. IMRI can ensure that the surgical goals have been reached. Future comparison of target volumes, integral volume doses, and patient outcomes are planned.
Gamma Knife Radiosurgery for Metastatic Brain Tumors
Authors: Park Yong Gou , Choi Jae Young , Chang Jin Woo , Chung Sang Sup
Published: April 2003

We reviewed our series of metastatic brain tumors treated by Gamma Knife Radiosurgery. From May 1992 to January 2001, 115 consecutive patients with 425 lesions were treated over 128 treatment sessions. Forty three patients were known to have died at the end of the recording period. The mean follow-up duration was 11.6 months and mean number of lesions was 3.5. The most common primary sites were lung and breast. Mean tumor volume was 4.2 cm3 and mean margin dose was 16.2 Gy. 6-month, 1-year, and 18-month survival rates were 73.6, 58, and 46%, respectively. Multivariate analysis revealed that higher KPS scores, no evidence of extracranial metastasis, and controlled primary disease were significantly related to longer survival. Adjuvant whole brain irradiation did not significantly influence on the prolongation of survival time and local control of radiosurgically treated lesions.
Radiosurgery and Stereotactic Radiation Therapy of Skull Base Meningiomas: Proposal of a Grading System
Authors: De Salles Antonio A.F. , Frighetto Leonardo , Grande Cesar V. , Solberg Timothy D. , Cabatan-Awang Cynthia , Selch Michael T. , Wallace Robert , Ford Judith
Published: April 2003

Objective: The development of a grading system to guide treatment selection, and predict treatment difficulty and outcome of skull base meningiomas infiltrating the cavernous sinus which are managed by stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT), based on an 8-year experience with stereotactic radiation of skull base meningiomas. Methods: T1 gadoliniun-enhanced magnetic resonance imaging (MRI) of 40 patients with skull base meningiomas, with or without prior surgery, who underwent radiosurgery or stereotactic radiation therapy from 1991 to 1998 at the UCLA Medical Center were reviewed, and the result of treatment was related to the tumor grade. Grade was based on tumor infiltration of the cavernous sinus and extension into adjacent structures. Treatment was performed with a linac-based system. The dose prescribed to the periphery of the tumor for SRS patients (n = 34) ranged from 12 to 22 Gy, and the maximum dose delivered to the tumor ranged from 24 to 46 Gy. SRT (n = 6). Treatment was planned using a single isocenter, usually prescribed to the 90% isodose volume, bringing the fractionation scheme to the maximal tolerance of the optic apparatus. The periphery dose ranged from 24 to 46 Gy with a maximum dose of 45 to 51 Gy. Clinical and MRI follow-up was performed every six months for the first 3 years and every year thereafter. Results: Grade I meningiomas were restricted to the cavernous sinus (n = 12). Grade II cavernous sinus meningiomas extended to the clivus and/or the petrous bone, without compression of the brainstem (n = 9). Grade III meningiomas had superior and/or anterior extension with compression of the optic nerve or tract (n = 9). Grade IV tumors compressed the brain stem (n = 8), and Grade V were bilateral lesions (n = 2). Tumor control rates were 90% for Grade I, 86% for Grade II, 86% for Grade III, 42% for Grade IV and no control for tumors Grade V. Complications were not related to tumor grade. Conclusion: This grading system correlated with outcome and difficulty in planning radiosurgery. Failure of treatment was more likely to occur in patients with higher Grade tumors.
Hindbrain and Cranial Nerve Dysmorphogenesis Result from Acute Maternal Ethanol Administration
Authors: Dunty Jr. William C. , Zucker Robert M. , Sulik Kathleen K.
Published: April 2003

Acute exposure of mouse embryos to ethanol during stages of hindbrain segmentation results in excessive cell death in specific cell populations. This study details the ethanol-induced cell loss and defines the subsequent effects of this early insult on rhombomere and cranial nerve development. Ethanol at a teratogenic dosage (2.9 g/kg) or a comparable volume of vehicle was administered in each of two intraperitoneal injections to pregnant C57BL/6J mice on gestational day (GD) 8, 8 h, and GD 8, 12 h (defined hereafter as GD 8.5). Ethanol-exposed GD 9 embryos, visualized in three dimensions using laser scanning confocal microscopy of LysoTracker Red fluorescence or Nile blue sulphate vital staining, displayed excessive apoptosis in the rostral hindbrain, specifically within rhombomeres 1–3, as well as in cranial neural crest cells and ectodermal placodes. Comparably treated embryos examined on GD 10.5–11 illustrated a disproportionate reduction in the length of the rostral hindbrain. Examination of plastic histological sections of GD 9 embryos and via scanning electron microscopy on GD 10 revealed deficiencies in the hindbrain, with a phenotype including abnormal rhombomere segmentation and an extremely small fourth ventricular roofplate. Whole-mount antineurofilament immunohistochemistry on GD 10.5 and GD 11 illustrated a variety of cranial nerve abnormalities ranging from fused or absent ganglia to ectopic or disorganized fibers. In addition, a delay in the development of the glossopharyngeal (IX) nerve/ganglia complex was observed. These hindbrain and cranial nerve abnormalities are discussed in the context of the genesis of human alcohol-related birth defects and neurodevelopmental disorder.