bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Butylated Hydroxyanisole and Some of Its Derivatives on Human Neutrophil Oxidative Burst: Chemiluminescence Evaluation
Authors: Braga Pier Carlo , dal Sasso Monica , Bovio Cinzia , Sgaragli Gian Pietro
Published: April 2003

An acute inflammatory response begins during the reperfusion phase following an ischemic insult in which polymorphonuclear neutrophils (PMNs) play an important role and the release of reactive oxygen species (ROS) causes further damage and a reduction in endogenous antioxidant storage. The ability of butylated hydroxyanisole (BHA) and some phenolic, aliphatic and aromatic BHA derivatives to reduce the human PMN oxidative burst evoked by particulate (Candida albicans and zymosan) or soluble stimulants [N-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol myristate acetate (PMA)] was investigated using luminol-amplified chemiluminescence. BHA and the derivative dt-BHA [3,5-di-t-butyl-4-hydroxyanisole] significantly reduced the PMN oxidative burst at concentrations ranging from 5 × 10–6 to 5 × 10–5 mol/l for C. albicans stimulation, while for zymosan stimulation, reduction was seen at concentrations ranging from 5 × 10–6 to 5 × 10–5 mol/l for BHA, and at concentrations ranging from 5 × 10–7 to 5 × 10–5 mol/l for dt-BHA, with dt-BHA being the most active. Another BHA derivative, Bu GAM 1, was active at 5 × 10–5 mol/l for C. albicans and at 5 × 10–6 to 5 × 10–5 mol/l for zymosan. The findings obtained with fMLP and PMA were very similar to those previously reported. ROS release is related to PMN killing activity, but the inhibition of the PMN oxidative burst induced by BHA and BHA derivatives did not significantly modify PMN phagocytosis or killing. It has recently been observed that dt-BHA has a spasmolytic action by inhibiting the influx of Ca2+ into cells through L-type Ca2+ channels, which means that a single molecule is capable of counteracting two major steps in the sequence of events triggered by ischemia-reperfusion injury, i.e. free radical release and Ca2+ overload.
Induction of Reversible Antifertility with a Crude Ethanol Extract of Citrullus colocynthis Schrad Fruit in Male Rats
Authors: Chaturvedi M. , Mali P.C. , Ansari A.S.
Published: April 2003

A crude 50% ethanol extract of Citrullus colocynthis Schrad was administered orally to male albino rats for evaluation of antifertility effects. The animals were divided into five groups: group A was a vehicle-treated control group; treatment groups B, C, and D received 100 mg/kg/day C. colocynthis extract for periods of 20, 40, and 60 days, respectively, and group E animals received the extract at 100 mg/kg/day for 60 days followed by 60 days of recovery. For androgenicity evaluation of the extract, the animals were divided into four groups: group F animals were castrated 30 days before the experiment to serve as controls, and group G, H, and I were subjected to castration 30 days before the experiments, followed by administration of fruit extract (100 mg/kg/day p.o.), testosterone propionate (0.01 mg/rat/alternate day s.c.), and fruit extract along with testosterone propionate, respectively, for 30 days. Significantly reduced cauda epididymis sperm motility and density, number of pups, fertility, and circulatory levels of testosterone were observed in all treatment groups. The weights of testes, epididymis, seminal vesicle, and prostate were significantly decreased in groups B, C, and D. The weights of all organs in the different groups of the androgenicity study were markedly decreased in group F when compared with group A, in group G when compared with group F, and in group I when compared with group H, and increased in group H when compared with group F. The serum testosterone levels also showed a similar pattern. The concentration of testicular cholesterol was significantly elevated, while protein, sialic acid, acid and alkaline phosphatase concentrations were decreased. The histoarchitecture of the testes showed degenerative changes in the seminiferous epithelium, arrest of spermatogenesis at the secondary spermatocyte stage, cytolysis, and the lumen filled with eosinophilic material. Histometric parameters except Sertoli cell nuclear area and number of round spermatids showed marked alterations. All altered parameters restored to normal in group E. No changes were observed in body weight, litter size, hematology, and serum biochemistry. In conclusion, a 50% ethanol extract of C. colocynthis showed an antiandrogenic nature, thereby reduced reversible infertility in male albino rats.
Needle Displacement during High-Dose-Rate Afterloading Brachytherapy Boost and Conventional External Beam Radiation Therapy for Initial and Local Advanced Prostate Cancer
Authors: Pellizzon A.C.A. , Salvajoli J.V. , Novaes P.E.R.S. , Maia M.A.C. , Ferigno R. , Fogaroli R.C.
Published: April 2003

Purpose: To determine the displacement of needles (ND) and its impact in the outcome of initial and locally advanced prostate cancer treated with conventional external beam radiation therapy (EBRT) and fractionated transrectal ultrasound-guided high-dose-rate afterloading brachytherapy (HDR-BT) as a boost. Methods and Materials: From 03/97 to 08/98 a total of 47 patients were eligible for study entry. Patients with 1992 AJCC clinical stage T3a or less and prostatic volume ≤60 cm3 were eligible. Prior to HDR-BT, all patients had a course of pelvic localized EBRT up to a median dose of 46 Gy (range 45–50.4). Results: Median age was 68 years (range 47–83) and median follow-up 48 months (range 36–53). Minimal or no needle displacement occurred in 17% (8/47) of patients. There were 61.7% (29/47) of patients who needed one correction and 21.3% (10/47) who needed two corrections. There were no correlations with ND (p = 0.130) and times of ND (p = 0.295) occurrence with bNED. The crude and actuarial biochemical controls (bNED) in 53 months for all patients were 87.2 and 82.3% respectively. Actuarial bNED after 4 years in patients without and with ND were 75 and 89.7% (p = 0.254). Discussion: There are many advantages when HDR-BT is used, but the most important ones are the capability of on-line dosimetry and quality control. The procedure is very conformal, with dose-volume histograms representing the administered dose, but we still need to wait for results of phase III open trials that analyze HDR-BT and conformal therapy.
Experiences with an Outpatient Relapse Program (Community Reinforcement Approach) Combined with Naltrexone in the Treatment of Opioid-Dependence: Effect on Addictive Behaviors and the Predictive Value of Psychiatric Comorbidity
Authors: Roozen H.G. , Kerkhof A.J.F.M. , van den Brink W.
Published: April 2003

Background: There is increasing interest in naltrexone, an opiate antagonist, in the treatment of opiate addicts. The effects of naltrexone are often compromised by a lack of compliance and drop-out. The effects of this compound are probably more favorable when combined with a psychosocial intervention such as the Community Reinforcement Approach (CRA). Aim: To explore the effects of a combination therapy (naltrexone plus CRA treatment) and the predictive value of sociodemographic and psychopathologic characteristics. Method: Using a before-and-after design, heroine addicts (n = 24) receiving a combined naltrexone plus CRA treatment are compared with a group (n = 20) on methadone maintenance therapy (reference group). Results: Over a period of 6 months, 58% (14/24) did not relapse, after 1 year at least 55% (12/22) still met the initial goal of continuous abstinence. At baseline, the treatment group and the reference group were similar on nearly all variables except for the number of times clients were arrested. Within the treatment group, a comparison was made between the continuous abstinent and those who relapsed into frequent opioid use. Differences were significant in the cluster-B personality disorders and in polydrug users. Conclusion: The combination of naltrexone plus intensive CRA in an outpatient setting appears to be promising. A high score on cluster-B and polydrug use is associated with relapse.
Pediatric Tumors of the Orbit and Optic Pathway
Authors: Schick Uta , Hassler Werner
Published: April 2003

We present an overview of the treatment and clinical outcome of 30 pediatric patients with orbital and optic pathway tumors cared for in our center from 1991 to 2002. Follow-ups were available for 48 months on average. Eight of 14 gliomas of the optic nerve or pathway were subtotally resected via a pterional approach. Two were totally resected with transection of the optic nerve, 2 were only biopsied and 2 were observed. One of 4 optic nerve sheath meningiomas in patients with good visual acuity was subtotally resected with decompression of the optic canal. Two were totally resected with transection of the prechiasmal optic nerve and 1 was only biopsied. Four infectious intra-/extraconal lesions were biopsied (transconjunctival approach) and treated with antibiotics. Two vascular intra-/extraconal tumors (hemangiomas) were removed via a transconjunctival approach and a lateral orbitotomy. The following histologies only occurred once: dermoid cyst, aneurysmal bone cyst, eosinophilic granuloma, fibrous dysplasia, osteopetrosis and rhabdomyosarcoma. The spectrum of pathology in pediatric orbital tumors is wide and requires multidisciplinary treatment.
Detection Rates for Genotyping Errors in SNPs Using the Trio Design
Authors: Geller Frank , Ziegler Andreas
Published: April 2003

One well-known approach for the analysis of transmission-disequilibrium is the investigation of single nucleotide polymorphisms (SNPs) in trios consisting of an affected child and its parents. Results may be biased by erroneously given genotypes. Various reasons, among them sample swap or wrong pedigree structure, represent a possible source for biased results. As these can be partly ruled out by good study conditions together with checks for correct pedigree structure by a series of independent markers, the remaining main cause for errors is genotyping errors. Some of the errors can be detected by Mendelian checks whilst others are compatible with the pedigree structure. The extent of genotyping errors can be estimated by investigating the rate of detected genotyping errors by Mendelian checks. In many studies only one SNP of a specific genomic region is investigated by TDT which leaves Mendelian checks as the only tool to control genotyping errors. From the rate of detected errors the true error rate can be estimated. Gordon et al. [Hum Hered 1999;49:65–70] considered the case of genotyping errors that occur randomly and independently with some fixed probability for the wrong ascertainment of an allele. In practice, instead of single alleles, SNP genotypes are determined. Therefore, we study the proportion of detected errors (detection rate) based on genotypes. In contrast to Gordon et al., who reported detection rates between 25 and 30%, we obtain higher detection rates ranging from 39 up to 61% considering likely error structures in the data. We conclude that detection rates are probably substantially higher than those reported by Gordon et al.
Exact Tests for the Analysis of Case-Control Studies of Genetic Markers
Authors: Neuhäuser Markus
Published: April 2003

Objectives: The association of a candidate gene with disease can be evaluated by a case-control study in which the genotype distribution is compared for diseased cases and unaffected controls. Usually, the data are analyzed with Armitage’s test using the asymptotic null distribution of the test statistic. Since this test does not generally guarantee a type I error rate less than or equal to the significance level α, tests based on exact null distributions have been investigated. Methods: An algorithm to generate the exact null distribution for both Armitage’s test statistic and a recently proposed modification of the Baumgartner-Weiss-Schindler statistic is presented. I have compared the tests in a simulation study. Results: The asymptotic Armitage test is slightly anticonservative whereas the exact tests control the type I error rate. The exact Armitage test is very conservative, but the exact test based on the modification of the Baumgartner-Weiss-Schindler statistic has a type I error rate close to α. The exact Armitage test is the least powerful test; the difference in power between the other two tests is often small and the comparison does not show a clear winner. Conclusion: Simulation results indicate that an exact test based on the modification of the Baumgartner-Weiss-Schindler statistic is preferable for the analysis of case-control studies of genetic markers.
Association Studies of QTL for Multi-Allele Markers by Mixed Models
Authors: Fan Ruzong , Jung Jeesun
Published: April 2003

In this paper, we extend association study methods of both Fan et al. [Hum Hered 2002;53:130–145], in which a quantitative trait locus (QTL) and a multi-allele marker are considered for trio families, and Fan and Xiong [Biostatistics 2003, in press], in which a QTL and a bi-allelic marker are considered for nuclear families. The objective is to build mixed models for association study between a QTL and a multi-allelic marker for nuclear families with any number of offspring. Two types of nuclear family data are considered: the first is genetic data of offspring from at least one heterozygous parents, and the second is genetic data of offspring of nuclear family. (1) For the data of offspring from at least one heterozygous parents, we assume that at least one parent is heterozygous at the marker locus, and we may infer clearly the transmission of parental marker alleles to the offspring. We show that it can be used in association study in the presence of linkage. The theoretical basis is the difference between the conditional mean of trait value given an allele is transmitted and the conditional mean of trait value given the allele is not transmitted from a heterozygous parent. To build valid models, we calculate the variance covariance structure of trait values of offspring. Besides, the reduction of the number of parameters is discussed under an assumption of tight linkage between the trait locus and the marker. (2) For the data of offspring of nuclear family, we show that it can be used in general association study. In this case, the theoretical basis is the difference between the conditional mean of trait values given an allele is transmitted from a parent and the population mean. Then, we calculate variance-covariance structure of trait values of offspring. (3) Based on the theoretical analysis, mixed models are built for each type of the data, and related test statistics are proposed for association study. By power calculation and comparison, we show that, in some instances, the proposed test statistics have higher power than that by collapsing alleles to be new ones. The proposed models are used to analyze chromosomes 4 and chromosome 16 data of the Oxford asthma data, Genetic Analysis Workshop 12.
Carcinoma of Pelvic Pouch following Restorative Proctocolectomy: Report of a Case and Review of the Literature
Authors: Negi Sanjay S. , Chaudhary Adarsh , Gondal Ranjana
Published: April 2003

One of the possible long-term complications following an ileoanal pouch procedure is the development of malignancy in the mucosa of the rectal stump. Only 10 such cases have been reported so far. We report the case of a 23-year-old male who had ulcerative colitis with high-grade dysplasia and underwent an ileoanal pouch procedure. He was found to have a malignancy in the rectal stump 5 years after surgery. The malignancy presented with symptoms of refractory pouchitis. Pouch excision was performed. The risk of developing malignancy in the rectal mucosa after an ileoanal pouch procedure mandates regular follow-up in these patients, with a high index of suspicion especially in patients with delayed onset pouchitis.
HHV-8 DNA Sequences in the Peripheral Blood and Skin Lesions of an HIV-Negative Patient with Multiple Eruptive Dermatofibromas: Implications for the Detection of HHV-8 as a Diagnostic Marker for Kaposi’s Sarcoma
Authors: Kazakov D.V. , Schmid M. , Adams V. , Cathomas G. , Müller B. , Burg G. , Kempf W.
Published: April 2003

Background: Multiple eruptive dermatofibroma (MEDF) is a rare disorder seen in immunocompromised patients, simulating Kaposi’s sarcoma (KS). Whereas KS is strongly associated with human herpesvirus 8 (HHV-8), the virus has never been detected in MEDF until now. Objective: To present a patient with MEDF who showed no signs of immunodeficiency but was seropositive for HHV-8 antibodies and demonstrated HHV-8 DNA both in the peripheral blood and lesional skin of MEDF. Methods: Clinical, histological and serological investigations were performed as well as polymerase chain reaction (PCR) studies and in situhybridization (ISH). Results: A 35-year-old white man with suspected KS was referred for evaluation of multiple pigmented nodules and patches. Biopsies revealed features of dermatofibroma, superficial fibrosing dermatitis and scar. One of the nodular lesions harbored HHV-8 DNA sequences. A faint amplification product was detected in the superficial fibrosing dermatitis lesion, while no HHV-8 sequences were found in normal skin and scar. Whole-blood samples and serum were positive for HHV-8. None of the skin lesions shown to harbor HHV-8 DNA sequences by nested PCR displayed a signal for HHV-8 RNA by ISH. Repetitive peripheral blood examinations did not reveal any serum antibodies against or antigens of HIV. Serum antibodies against the HHV-8 capsid antigen orf 65.2 were detected. Conclusion: Results of PCR studies and ISH indicate that the presence of HHV-8 in the lesional tissue was probably blood-borne due to viremia and not due to viral replication in tumor cells. The presence of HHV-8 is not fully restricted to KS. The differential diagnosis of KS and its simulators should be based on an integrative analysis of all available clinicopathological and molecular data and should not rely exclusively or predominantly on the presence or absence of HHV-8.
Treatment of Old World Cutaneous Leishmaniasis with Intralesionally Injected Meglumine Antimoniate Using a Dermojet Device
Authors: Bogenrieder Thomas , Lehn Norbert , Landthaler Michael , Stolz Wilhelm
Published: April 2003

Pentavalent antimonial compounds, the mainstay in the treatment of the various forms of leishmaniasis, have considerable toxicity, are difficult to administer and expensive. We describe a safe and efficient therapeutic modality using a spring-loaded and air-powered device for the intralesional injection of a high-velocity meglumine antimoniate microspray in a patient with cutaneous leishmaniasis.
It Is True that, when Langerhans Cells Migrate from the Skin to the Lymph Node, They Are Transported via Lymph Vessels
Authors: Sugiura Keiji , Shamoto Mikihiro , Sakamoto Nao , Shinzato Masanori , Osada Akiko , Sugiura Mariko , Hayakawa Ritsuko , Kato Yoshimi
Published: April 2003

Background: Generally, Langerhans cells deliver antigen information from the skin to the draining lymph nodes via lymph vessels. Methods: By immunohistopathology, we investigated the delivery route of Langerhans cells in human skin using CD1a and S-100 protein antibodies. Results: We noted CD1a- and S-100-positive Langerhans cells in the lymph vessels of the dermis. These were shaped like dendritic cells and presented with some lymphocytes, melanophages, melanin granules and lymph in the same vessels. Conclusion: These observations support the concept that Langerhans cells deliver antigen peptides to regional lymph nodes via afferent lymph vessels.
Dysgerminoma with a Slightly Elevated α-Fetoprotein Level Diagnosed as a Mixed Germ Cell Tumor after Recurrence
Authors: Aoki Yoichi , Kase Hiroaki , Fujita Kazuyuki , Tanaka Kenichi
Published: April 2003

A pure dysgerminoma shows a normal serum α-fetoprotein level, and mixed germ cell tumors containing endodermal sinus tumor elements have elevated serum α-fetoprotein levels, ranging from >100 to far higher than 1,000 ng/ml. A 40-year-old woman was diagnosed as having a stage Ia pure dysgerminoma with a slight α-fetoprotein elevation (11 ng/ml), after a staging laparotomy, because we could not find any yolk sac element in the original tumor. After 44 months, she had a pelvic recurrent tumor with a significant elevation of the serum α-fetoprotein concentration (1,520 ng/ml); histological examination of a needle biopsy specimen revealed a typical yolk sac tumor. Eventually, her initial tumor was diagnosed as a mixed germ cell tumor. The patient was successfully treated with seven courses of chemotherapy and has been disease free for 22 months. It is necessary to be aware of the possibility of a mixed germ cell tumor containing a yolk sac element, even when the α-fetoprotein level is only slightly elevated.
Clinical Significance of High nm23-H1 Expression in Intraepithelial Neoplasia and Early-Stage Squamous Cell Carcinoma of the Uterine Cervix
Authors: Wang Po-Hui , Ko Jiunn-Liang , Chang Han , Lin Long-Yau
Published: April 2003

Seventy-two cervical pathology specimens, consisting of samples of cancer and high- and low-grade intraepithelial neoplasia, were used in a study exploring the involvement of nm23-H1/NDP kinase in carcinogenesis or recurrence. Additionally, the relationships between immunohistochemical expression of nm23-H1 and various clinicopathological variables for early-stage cervical cancer were evaluated. The nm23-H1 expression for high-grade cervical intraepithelial neoplasia and squamous cell carcinoma samples was significantly elevated when compared to low-grade analogs. Only deep stromal invasion was significantly associated with high nm23 expression. Moreover, a high cumulative recurrence hazard was demonstrated for the high nm23 expression group. In conclusion, high nm23-H1 expression may induce cellular proliferation for the progression from low- to high- grade intraepithelial neoplasia, with the subsequent emergence of invasive carcinoma as well as deep stromal invasion, and can be used as an indicator of prognosis.
Investigation of Placental Stem Villi Arteries in Fetally Growth-Restricted Pregnancies: A Multivariate Analysis
Authors: Guiot C. , Russo R. , Sciarrone A. , Biolcati M. , Piccoli E. , Kaufmann P. , Todros T.
Published: April 2003

Thirteen placentas were studied from 5 normal pregnancies and 8 from pregnancies complicated by fetal growth restriction (4 with present, 3 with absent, and 1 with reversed end-diastolic velocities at Doppler interrogation of the umbilical arteries). On immunohistochemically stained slides, the diameter (d) and the wall thickness (t) of the arterial vasculature of the stem villi were measured for a total of approximately 10,000 vessels. A multivariate ‘mixed effect model’ statistical analysis was performed using d and t as dependent variables and gestational age, delivery mode, fetal and placental weight, the degree of vascular collapse and Doppler blood flow patterns as independent variables. Gestational age, Doppler pattern and the degree of vascular collapse significantly affected both d and t, the mode of delivery influenced d while fetal and placental weights scarcely affected the dependent variables. The above parameters should therefore be taken into account when investigating placental stem vessel morphometry.
Conventional and Computerized Antepartum Telecardiotocography
Authors: Di Lieto Andrea , Giani Umberto , Campanile Marta , De Falco Marianna , Scaramellino Mariangela , Papa Rosa
Published: April 2003

The study assessed the agreement in cardiotocogram interpretation between the 2CTG computerized system and experienced and inexperienced observers involved in a telecardiotocography project called ‘TOCOMAT’. Both observers and computer analyzed FHR baseline, FHR variability, and number of large accelerations and of decelerations. The k coefficient was calculated for the statistical analysis. The interobserver agreement about the evaluation of the FHR baseline and of the large accelerations was good; it was poor about the assessment of the FHR variability and the decelerations. Similar results were obtained for the agreement among observers and computer. The use of a computerized system provides exact values for most CTG parameters; the experts, however, should rely both on clinical features and on the computerized interpretation, to make decisions about management.
Comparison of Neonatal Effects of Epidural and General Anesthesia for Cesarean Section
Authors: Sener Elif Bengi , Guldogus Fuat , Karakaya Deniz , Barıs Sibel , Kocamanoglu Serhat , Tur Ayla
Published: April 2003

We assessed the influence of anesthetic technique for cesarean section on neonatal outcome. Thirty parturient women (ASA I/II) were randomly allocated into two groups. In Group GA general anesthesia was induced with 4 mg·kg–1 thiopental and 1.5 mg·kg–1 succinylcholine. In group EA epidural anesthesia was performed with 20 ml 0.375% bupivacaine through L3–4 inter-space. 1-min Apgar scores were significantly higher in group EA (p < 0.001). Neurologic and Adaptive Capacity scores at 2 and 24 h were higher in group EA (p < 0.001). In terms of blood gas values, umbilical arterial pH and pO2 values were higher in group EA (p < 0.05 and p < 0.001, respectively). The first breast-feeding intervals were found to be shorter in group EA (p < 0.001). We conclude that in terms of better Apgar and NAC scores, acid-base status and earlier initiation of breast-feeding, the epidural anesthesia may be preferred to general anesthesia in cesarean section.
Exploration of the Role of the Upper Brainstem in Motor Control
Authors: Nandi D. , Stein J.F. , Aziz T.Z.
Published: April 2003

The rostral areas of the brainstem have been extensively studied in higher mammals and to a lesser extent in humans in the last two decades, looking for anatomical, electrophysiological and neurochemical evidence of involvement in the initiation and control of voluntary movement. This has come with the realisation that the axial symptoms of advanced Parkinson’s disease (PD), like akinesia, postural impairment and gait freezing, are relatively less responsive to current medical and surgical treatments directed primarily at the basal ganglia and thalamus. The pedunculopontine nucleus (PPN) is one such area of interest. We have found that lesioning and electrical stimulation at high frequencies of the PPN region in the normal behaving primate induces akinesia, and low frequency stimulation can induce tremor. Micro-injections of gamma-aminobutyric acid (GABA) receptor A agonist, muscimol, into the PPN decreases activity. In the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated Parkinsonian primate model, bicuculline, a GABAA antagonist, can alleviate akinesia when infused into the PPN region. This may suggest new targets for treating the intractable akinetic symptoms of advanced PD.
Use of Digitized Fluorescein Angiogram System to Guide Laser Treatment of Diabetic Macular Edema: A New Technique
Authors: Ladas Ioannis D.
Published: April 2003

We describe our technique to guide laser treatment in diabetic patients with clinically significant macular edema using a digitized fluorescein angiogram system. A pretreatment red-free photograph overlaid on a fluorescein angiogram is processed with the aid of the digitized fluorescein angiogram system in order to include all the important traces on it. The processed red-free image is used by the surgeon as a guide to the laser photocoagulation, improving treatment accuracy and safety for patients with diabetic macular edema.
Phacoemulsification and Intraocular Lens Implantation Combined with Trabeculotomy for Open-Angle Glaucoma and Coexisting Cataract
Authors: Kubota Toshiaki , Touguri Ichiro , Onizuka Naoko , Matsuura Toshie
Published: April 2003

Objective: To study the outcome of phacoemulsification and intraocular lens implantation combined with trabeculotomy. Methods: We performed trabeculotomy combined with phacoemulsification and foldable lens implantation in 25 eyes with open-angle glaucoma and coexisting cataract in 18 patients. The series comprised 9 males (13 eyes) and 9 females (12 eyes). Mean age of the patients was 73.4 ± 10.9 years (45–87 years). Mean follow-up period was 14.3 ± 6.0 months (6–24 months). Results: The preoperative intraocular pressure was 21.4 ± 3.7 mm Hg. The postoperative intraocular pressure 6 months after the surgery was 12.8 ± 3.4 mm Hg. A postoperative tension spike (>30 mm Hg) was observed in 2 eyes. Six months after the operation, the intraocular pressure was controlled under 21 mm Hg in all eyes, and under 16 mm Hg in 18 eyes. The medication score (one point per antiglaucomatous medication) was 2.0 ± 1.6 before the surgery and 0.4 ± 0.7 after the surgery. The mean refractive error after the operation was –0.8 ± 0.7 D (range –2.4 to 0 D). The deviation of the actual refractive error from the predicted one was +0.29 ± 0.54 D (range –0.52 to +1.10 D). Conclusion: The outcome of the combined operation for open-angle glaucoma and coexisting cataract was promising.
Theoretical Models for the Mechanisms of Benign Paroxysmal Positional Vertigo
Authors: House Matthew G. , Honrubia Vicente
Published: April 2003

Benign paroxysmal positional vertigo (BPPV) is a common vestibular disorder resulting from a malfunction of the semicircular canal. Prior studies attempting to elucidate the mechanics of BPPV have focused on clinical and laboratory findings, and have discussed theoretical aspects only in qualitative terms. The goal of this study is to create a mathematical description of BPPV mechanics based on biophysical principles, in order to improve the physiopathological understanding of the most common varieties of the disorder, canalithiasis and cupulolithiasis. First, the abnormal stimulus being applied to the vestibular system during BPPV episodes is estimated by an analysis of the vestibulo-ocular reflex (VOR) response of clinical BPPV patients. The magnitude and time course of the head motion stimulus that would, in a normal test subject, produce a VOR response similar to that observed during BPPV nystagmus are inferred from eye motion data using an inverse transfer function approach. Next, physicomathematical models to describe the mechanics of the abnormal stimulations of the crista are created: the cupulolithiasis model is based on the principle that dense particulate matter becomes attached to the cupula of affected patients and effectively changes the specific gravity of the cupula; the canalithiasis model is based on the hydrodynamic effects from a cluster of particles falling within the canal endolymph. The stimuli predicted by these two models are compared to the stimuli estimated from physiological and clinical studies. The model predictions are found to be consistent with the empirical evidence for a reasonable set of model parameters. The cupulolithiasis model predicts a value of 0.69 µg as the mass of particles contributing to the disorder. The canalithiasis model predicts a value of 0.087 µg. These results support and expand our understanding of the mechanisms underlying the production of the cupulolithiasis and canalithiasis varieties of vertigo in humans. On the basis of these models, several predictions that can help the clinician improve the evaluation of BPPV patients are discussed.
Involvement of CCR3-Reactive Chemokines in Eosinophil Survival
Authors: Shinagawa Kazuhiko , Trifilieff Alexandre , Anderson Gary P.
Published: April 2003

Background: Although eosinophils undergo apoptosis and are thus eliminated from sites of inflammation, they survive longer if survival factors, such as IL-3, IL-5 and GM-CSF, are present. However, it is often observed that some eosinophils survive even when incubated without any survival factors (spontaneous survival). The aim of the present study was to investigate what kind of factor(s) is associated with this spontaneous survival of eosinophils. Methods: Eosinophils were purified from bronchoalveolar lavage of antigen-exposed Balb/c mice and stained with propidium iodide to detect apoptotic ones. Results: We found that the spontaneous survival of eosinophils was reduced by treatment of the cells with anti-CC chemokine receptor-3 (CCR3) antibody (Ab). Moreover, eotaxin-1, eotaxin-2, and eotaxin-3 all prolonged the survival of eosinophils in a dose-dependent fashion. The survival-prolonging effect of eotaxin-1 was enhanced in the presence of eotaxin-3, indicating that these chemokines might work synergistically. Conclusion: We speculate that eosinophils survive longer under the influence of CCR3-reactive chemokines, which aid the infiltration of these cells into the tissue and that eosinophils may survive even longer if they encounter survival factors at local inflammatory sites.
Stereochemical Considerations on Concomitant Allergic Contact Dermatitis to Ester of the cis-trans Isomeric Compounds Maleic Acid and Fumaric Acid
Authors: Hansson C. , Thörneby-Andersson K.
Published: April 2003

Allergic contact dermatitis from esters of fumaric acid or esters of maleic acid is rare. The case of a chemist with allergic reactions to esters both of fumaric acid and of maleic acid is presented. Extremely high sensitivity of the patient to diethyl fumarate was noted. The formation of identical complete antigens from esters of these two cis-trans isomeric acids may be an explanation of the patient’s double allergy. This is discussed from a stereochemical point of view. These stereochemical considerations point to a general mechanism where cis-trans isomeric α,β-unsaturated carbonyl compounds are converted into the same complete antigen.
Effects of Selective Nitric Oxide Synthase Inhibition on IGF-1, Caspases and Cytokines in a Newborn Piglet Model of Perinatal Hypoxia-Ischaemia
Authors: Peeters-Scholte Cacha , Koster Johanna , van den Tweel Evelyn , Blomgren Klas , Hamers Nicole , Zhu Changlian , van Buul-Offers Sylvia , Hagberg Henrik , van Bel Frank , Heijnen Cobi , Groenendaal Floris
Published: April 2003

Selective inhibition of neuronal and inducible nitric oxide synthase (NOS) with 2-iminobiotin previously showed a reduction in brain cell injury. In the present study, we investigated the effects of 2-iminobiotin treatment on insulin-like growth factor-1 (IGF-1) expression, caspase activity and cytokine expression in a newborn piglet model of perinatal hypoxia-ischaemia. Newborn piglets were subjected to 1 h of hypoxia-ischaemia and were treated intravenously with vehicle or 2-iminobiotin. Vehicle-treated piglets showed reduced IGF-1 mRNA expression and increased caspase-3 activity and DNA fragmentation. 2-Iminobiotin treatment, administered immediately upon reperfusion, prevented these observations. No differences in caspase-8 and -9 activity and cytokine [interleukin (IL)-1α/β, IL-6, tumour necrosis factor (TNF)-α, transforming growth factor (TGF)-β] mRNA expression were demonstrated between vehicle- and 2-iminobiotin-treated piglets at 24 h following hypoxia-ischaemia. IGF-1 mRNA correlated inversely with caspase-3 and transferase-mediated dUTP-biotin in situ nick end labelling score in the cortex, but positively with caspase-8. Cytokine mRNA did not correlate with IGF-1 mRNA, caspase-3 activity or DNA fragmentation. The present results indicate that the previously demonstrated neuroprotective effect of 2-iminobiotin treatment after perinatal hypoxia-ischaemia coincided with a preservation of the endogenous IGF-1 production and reduced caspase-3 activity, but not with a significant decrease in cytokine production.
Influence of Growth Hormone Therapy on Pituitary and Lumbar Spine Astrocytomas
Authors: Mohn Angelika , di Ricco Laura , de Santis Antonio , Tartaro Armando , Capanna Rita , Chiarelli Francesco
Published: April 2003

We report on a male patient with an inactive pituitary and lumbar astrocytoma. He presented with panhypopituitarism at the age of 16 and received growth hormone replacement therapy for one year. During this period the pituitary mass increased substantially and showed subsequently a consistent shrinkage once treatment was stopped. The lumbar lesion stayed stable for the whole period of observation. The presumable rGH related change of the pituitary astrocytoma underlines the importance of careful follow-up of children with growth hormone deficiency secondary to treatment for brain tumors. Substitution therapy with rGH requires further and longer studies before it can be recommended with absolute reassurance in children with subtotal resection of a pituitary astrocytoma.
Tumors and Malformations of the Caudal Spinal Axis
Authors: Lemire Ronald J. , Pendergrass Thomas W. , Beckwith J. Bruce , Ellenbogen Richard G.
Published: April 2003

The early development of the neural tube has been well studied in animals and humans. After axial determinants have been accomplished the processes of primary and secondary neurulation take place. Successful completion results in a spinal cord that has arisen from primary neurulation and a lower sacro-coccygeal portion from secondary neurulation. The latter region is the site of numerous skin-covered clinical lesions, which include tumors and malformations. A listing of selected features in 764 cases of skin-covered sacrococcygeal lesions is presented. The manner in which these lesions arise and the potential for genetic factors being responsible is discussed.
Pediatric Temporal Lobectomy for Epilepsy
Authors: Sinclair D. Barry , Aronyk K. , Snyder T. , McKean J. , Wheatley M. , Bhargava R. , Hoskinson M. , Hao C. , Colmers W.
Published: April 2003

Background: Temporal lobectomy in adults is an accepted form of treatment for patients with intractable complex partial seizures. There have been few long-term studies of children undergoing temporal lobectomy for epilepsy. Methods: We reviewed the pediatric cases of temporal lobectomy for intractable epilepsy performed by the Comprehensive Epilepsy Program at the University of Alberta Hospitals between 1988 and 2000. All patients had preoperative and postoperative clinical evaluations, seizure charts, drug levels, EEG, CT/MRI, long-term video EEG monitoring and neuropsychological testing. The patients were reassessed at 6 weeks, 6 months and 1 year postoperatively, then yearly. The duration of follow up was 1–10 years (mean 5 years). Results: Forty-two patients were studied (25 males and 17 females). Age at surgery ranged from 18 months to 16 years. The interictal EEG was abnormal in 38 of the 42 patients. Twenty-two patients had focal epileptic discharge and 1 had generalized epileptic discharge. Focal slowing was seen in 9 patients and diffuse slowing in 5 patients. CT scan was abnormal in 17 of 39 patients and normal in 22 of 39. MRI was abnormal in 34 of 42 patients and normal in 8 of 42. Pathology included brain tumors in 14 patients, mesial temporal sclerosis in 8, focal cortical dysplasia in 4, tuberous sclerosis in 4, dual pathology in 4, porencephalic cyst in 1 and normal pathology or gliosis in 6. Thirty-three of 42 patients (78%) were seizure-free following surgery and an additional 5 (12%) had a decrease in seizure frequency. Three patients had complications, but there were no deaths. Conclusion: Temporal lobectomy is a safe and effective treatment for children with intractable complex partial seizures. Seventy-eight percent of patients are seizure-free following the surgery and there are few complications. MRI is superior to CT scan for detection of temporal lobe pathology yet failed to detect abnormalities in some patients. The most common pathologies found were brain tumors, mesial temporal sclerosis and developmental lesions. In addition to seizure control, many patients experienced improvement in cognitive and psychosocial function following surgery.
Diabetes mellitus and Lung Function
Authors: Boulbou Mary S. , Gourgoulianis Konstantinos I. , Klisiaris Vasilios K. , Tsikrikas Thomas S. , Stathakis Nikolaos E. , Molyvdas P.A.
Published: April 2003

Objectives: To assess the nature of pulmonary dysfunction in type 1 diabetes and the relationship of pulmonary function tests to diabetic factors and complication. Subjects and Methods: Sixteen type 1 diabetic patients and 26 control subjects matched for age and sex were studied. We performed spirometry measurements and measured pulmonary diffusing capacity (DLCO) in sitting and supine position by the single-breath method corrected by alveolar volume (VA). Glycosylated hemoglobin (HbAIc), retinopathy and microalbuminuria were included as parameters of metabolic control and diabetic complications. Results: Diabetic patients showed a significant reduction of the following pulmonary function tests (% predicted value) as compared with control subjects: total lung capacity (TLC, 92.6 ± 14.5 vs. 113.9 ± 17.5, p < 0.001), lung diffusing capacity in sitting position (DLCO, 90.4 ± 21.1 vs. 107.7 ± 15.6, p = 0.004), lung diffusing capacity in supine position (DLCO, 88.3 ± 19.3 vs. 111.9 ± 19.9, p = 0.001). The differences in diffusing capacity corrected by alveolar volume in sitting and supine position (DLCO/VA) were not significant. By changing the posture from sitting to supine position both diabetic patients and control subjects significantly increased DLCO/VA (103.4 ± 17.7 vs. 112.7 ± 22.3, p = 0.046 and 99.5 ± 13.4 vs. 114.4 ± 13, p < 0.001, respectively). There was no correlation between pulmonary function tests and diabetic complications. Conclusion: These data indicate that type 1 diabetic patients showed reduced TLC and DLCO, features of pulmonary restrictive dysfunction. There was no correlation between abnormal pulmonary function and the presence of other diabetic complications.
Determinants of Left Ventricular Hypertrophy and Its Progression in High-Flux Haemodialysis
Authors: Kong Chiew H. , Farrington Ken
Published: April 2003

Aim: To identify factors contributing to the development and progression of left ventricular hypertrophy (LVH) in patients on high-flux haemodialysis. Method: Fifty patients without clinical cardiac disease underwent baseline echocardiography, related measurements and follow-up studies 6–12 months later. Results: Residual urea clearance was lower (0.7 ± 1.1 vs. 2.2 ± 2.4 ml/min; p = 0.034) while systolic blood pressure (162 ± 21 vs. 147 ± 11 mm Hg; p = 0.003), duration of dialysis dependence (38 ± 37 vs. 17 ± 13 months; p = 0.004) and interdialytic weight gain (1.98 + 0.84 vs. 1.32 + 1.08 kg; p = 0.026) were higher in those with LVH. Parathyroid hormone changed less in those whose LVH regressed (186 ± 89 vs. 303 ± 280 pg/ml; p = 0.032). Regression did not occur when parathyroid hormone was >300 pg/ml. ACE gene polymorphism did not affect LVH development or progression. Conclusion: Systolic hypertension, duration of dialysis dependence and high interdialytic weight gains promote LVH. Hyperparathyroidism retards LVH regression.
Bone Mass Cannot Be Predicted by Estimations of Frailty in Elderly Ambulatory Women
Authors: Gerdhem Paul , Ringsberg Karin A.M. , Magnusson Håkan , Obrant Karl J. , Åkesson Kristina
Published: April 2003

Background/Methods: High biological age, or frailty, a possible risk factor for fragility fracture, and its relation to known risk factors for fracture (low bone mineral density (BMD), low muscle strength, poor gait performance and poor balance, previous falls, previous fractures and future risk of falls) were investigated in 993 randomly selected 75-year-old women. Frailty, which has no accepted definition, was here defined as a subjective immediate impression of an individual’s general health appearance and was transferred into an arbitrary scale. 993 individuals were scored by at least one of four observers. Results: The frailty score and BMD were not correlated. A high frailty score was significantly correlated to poor gait (r = 0.53–0.59, p < 0.0001), poor balance (r = –0.49, p < 0.0001), low muscle strength (r = –0.25 to –0.41, p < 0.0001), low activity level (r = –0.43, p < 0.0001) and a high risk of falling (r = 0.24, p < 0.0001). The group of women who had experienced at least one fall the previous year had a higher frailty score (p < 0.0001) compared to those who had not. Women who had sustained a hip or femoral fracture after the age of 70 had a higher frailty score than women with no earlier fracture at all. Conclusions: Bone mass cannot be predicted by our subjective frailty score in elderly, ambulant women. Since a high frailty score correlates with factors that affect or are likely to affect fall propensity, this could indicate that a high frailty score is a risk factor for fracture, independent of bone mass. Frailty may be regarded as a complex risk factor, including several assessments that can be objectively measured. Whether estimation of frailty is a method to improve the assessment of the patient at risk for a fragility fracture is yet to be proven and can only be shown in a prospective study of fracture occurrence.
A New MF59-Adjuvanted Influenza Vaccine Enhances the Immune Response in the Elderly with Chronic Diseases: Results from an Immunogenicity Meta-Analysis
Authors: Banzhoff Angelika , Nacci Pantaleo , Podda Audino
Published: April 2003

Background: The elderly are at a higher risk of morbidity and mortality associated with influenza infection than younger adults, but get less protection from conventional vaccination. Objective: We conducted a meta-analysis of all available data from clinical trials in the elderly on a recently introduced MF59-adjuvanted influenza vaccine to determine its immunogenicity and safety in subjects with underlying chronic disease who are at highest risk of influenza infection. Methods: Data on immunogenicity and safety from 3,600 subjects immunized with either the MF59-adjuvanted or conventional comparator influenza vaccine in 13 clinical trials were analyzed by disease history. Geometric mean haemagglutination inhibition titres (GMTs) and differences between the vaccine groups were compared using two-way analysis of variance. Differences between vaccine groups in the percentages with post-immunization reactions were assessed using chi-squared test and Fischer’s exact test. Results: At 28 days the adjuvanted:comparator GMT ratio for the A/H3N2 antigen was 1.18 in healthy elderly subjects and 1.43 in elderly subjects with chronic disease (p = 0.004). The respective GMT ratios were 1.17 versus 1.37 for the B antigen (p = 0.065) and 1.10 versus 1.17 for the A/H1N1 antigen (p = 0.41). Although post-immunization reactions were more common in the group receiving the adjuvanted vaccine, these were predominantly mild and transient, and none were serious. Conclusions: The MF59-adjuvanted influenza vaccine is more immunogenic in elderly subjects than conventional non-adjuvanted influenza vaccines and especially so in those with chronic disease. Therefore, since its safety profile is clinically acceptable, this adjuvanted vaccine represents an excellent option for influenza immunization of elderly subjects at highest risk of complications.