bluuebunny/crossref_metadata_2025 huggingface dataset:
The Thrombopoietin Level in the Cord Blood in Premature Infants Born to Mothers with Pregnancy-Induced Hypertension
Authors: Tsao Po-Nien , Teng Ru-Jeng , Chou Hung-Chieh , Tsou Kuo-Inn
Published: April 2003

Objectives: To investigate the level of thrombopoietin in the cord blood of preterm infants, and its relationship with neonatal platelet count and pregnancy-induced hypertension. Study Method: Thrombopoietin levels in the cord blood of preterm neonates, with or without maternal pregnancy-induced hypertension, were measured by enzmye-linked immunosorbent assay. Results: The platelet count was significantly lower in very low birth weight infants, infants with maternal pregnancy-induced hypertension, and infants with maternal thrombocytopenia. Neonatal thrombocytopenia was associated with maternal pregnancy-induced hypertension and very low birth weight. The neonatal platelet count was correlated significantly with the birth weight and the maternal platelet count. There was no difference in the cord blood level of thrombopoietin between infants born to mothers with pregnancy-induced hypertension and those without. No correlation was found between the thrombopoietin level and the neonatal platelet count. A positive correlation between the cord blood thrombopoietin and the maternal platelet count was identified. Conclusion: Maternal pregnancy-induced hypertension and very low birth weight were significantly associated with thrombocytopenia in premature infants, which cannot be explained by decreased thrombopoietin level.
Reduction of Brain Volume Correlates with Behavioral Changes in Queen Ants
Authors: Julian Glennis E. , Gronenberg Wulfila
Published: April 2003

The behavior of reproductive female ants distinctly changes during the transition from virgin to mature, egg-laying queen. A winged female ant flies only once during her lifetime when she engages in the nuptial flight. Once she is mated she sheds her wings, excavates a nest and starts laying eggs, the basis for her future colony. We show for two species of harvester ants that this transition is accompanied by changes in the performance of behavioral tests: flying virgins are positively phototactic and prefer open areas, whereas young queens prefer the dark, avoid open areas and, given the opportunity, dig into the soil. These behavioral changes coincide with morphological changes in the brain. The brains of mature queens are significantly smaller than those of virgin females at the time of their mating flight. A disproportionately large shrinkage occurs in the medulla and other parts of the visual system during the early adult life of the queen. The brain reduction appears to be adaptive as mature queens show reduced behavioral repertoires and live in the dark. In contrast to virgin females, they do not rely on vision and might increase their fitness by reducing metabolically costly neural tissue.
The Effects of Spatially Separated Call Components on Phonotaxis in Túngara Frogs: Evidence for Auditory Grouping
Authors: Farris Hamilton E. , Rand A. Stanley , Ryan Michael J.
Published: April 2003

Numerous animals across disparate taxa must identify and locate complex acoustic signals imbedded in multiple overlapping signals and ambient noise. A requirement of this task is the ability to group sounds into auditory streams in which sounds are perceived as emanating from the same source. Although numerous studies over the past 50 years have examined aspects of auditory grouping in humans, surprisingly few assays have demonstrated auditory stream formation or the assignment of multicomponent signals to a single source in non-human animals. In our study, we present evidence for auditory grouping in female túngara frogs. In contrast to humans, in which auditory grouping may be facilitated by the cues produced when sounds arrive from the same location, we show that spatial cues play a limited role in grouping, as females group discrete components of the species’ complex call over wide angular separations. Furthermore, we show that once grouped the separate call components are weighted differently in recognizing and locating the call, so called ‘what’ and ‘where’ decisions, respectively.
Effect of Cervitec® on Mutans Streptococci in Plaque and on Caries Formation on Occlusal Fissures of Erupting Permanent Molars
Authors: Araujo A.M.P.G. , Naspitz G.M.C.C. , Chelotti A. , Cai S.
Published: April 2003

The aim of this study was to evaluate the effect of Cervitec® on the abundance of mutans streptococci(MS) in occlusal dental plaque and on 2-year caries increment of partly erupting first permanent molars. Sixteen healthy schoolchildren aged 6–8 years, with at least 2 sound contralateral partly erupted permanent molars, received diet counselling and daily parental supervised toothbrushing with a fluoride dentifrice. Stimulated saliva samples were collected at baseline and after 1 year to evaluate MS levels. In a split-mouth design, Cervitec varnish was applied to one of the teeth at baseline and after 3 and 6 months, while the other tooth in the same jaw was a control. At the 9-month follow-up the teeth were in occlusal contact. At this time, varnish was not applied. At 3 and 6 months after the first application of varnish a significant suppression of MS was observed in plaque. Caries investigations, performed at baseline and every 3 months during the 2 years after the start of the study, showed that all the teeth treated with the varnish were free of caries after 2 years, whereas 8/16 control teeth developed incipient caries. In conclusion, our results suggest that treatment with Cervitec reduces MS in plaque on erupting permanent molars and can lead to a significant decrease in caries incidence.
Calcipotriol Plus Short-Contact Dithranol: A Novel Topical Combination Therapy for Chronic Plaque Psoriasis
Authors: Monastirli A. , Georgiou S. , Pasmatzi E. , Sakkis T. , Badavanis G. , Drainas D. , Sagriotis A. , Tsambaos D.
Published: April 2003

The purpose of this double-blind randomised parallel-group study was to compare the efficacy and safety of short-contact treatment with dithranol ointment (2%) with its combination with calcipotriol ointment (50 µg/g) in 2 groups of in-patients with chronic plaque psoriasis. The patients of the first group (n = 23) topically applied dithranol once daily for 30 min and the vehicle of calcipotriol twice daily. The patients of the second group (n = 23) used a single topical application of dithranol for 30 min daily and additionally applied calcipotriol twice daily. The extent and the severity of psoriasis were assessed by means of psoriasis area and severity index score (PASI score) before the onset of the 6-week therapy and weekly thereafter. The difference between the two groups with regard to the mean PASI score became statistically significant already after the first week of treatment and remained so until the end of the trial. No significant differences were observed between the two groups with respect to the cutaneous adverse events. These findings indicate that the addition of calcipotriol ointment to short-contact dithranol markedly augments the therapeutic efficacy of the latter in chronic plaque psoriasis and impressively accelerates the response of psoriatic plaques to this well-tolerated regimen.
The Response of Normal Human Skin to Single and Repeated Applications of Dithranol Cream: An Immunohistochemical Assessment
Authors: Swinkels O.Q.J. , Prins M. , Birker L.W.J. , Gerritsen M.J.P. , van der Valk P.G.M. , van de Kerkhof P.C.M.
Published: April 2003

The irritative response of uninvolved skin is a serious limitation of dithranol therapy in psoriasis. A characterisation in cell biological terms may be helpful in finding an effective counteraction to this well-known irritation. Therefore, we studied the effect of single and repeated applications of dithranol on normal human skin. Besides a clinical evaluation, we studied aspects of epidermal proliferation, differentiation and inflammation. On day 2, after single dithranol challenge, we observed an induction of both the cornified envelope precursor protein involucrin and the cross-linking enzyme transglutaminase I. Subsequently, epidermal hyperproliferation was observed with a maximum on day 8. The epidermal response to dithranol appears to be a reinforcement of the barrier function. Remarkably, however, filaggrin was found to be decreased. Profilaggrin breakdown might be an attempt to compensate for xerosis of uninvolved skin that accompanies dithranol therapy. T lymphocytes and to a lesser extent polymorphonucleocytes were found to be significantly increased. The reduction of Langerhans cells suggests a dose-dependent toxic effect of dithranol or one of its metabolites on Langerhans cells. The dynamics in the induction of changes after repeated challenge are comparable with those after single challenge. However, the induction of hyperproliferation following repeated application appeared to continue between day 8 and 12. Based on the dynamics of dithranol-induced irritation, it may be of interest to study the efficacy of intermittent dithranol treatment. Our results indicate that an optimal timing for biopsies in future dithranol irritation studies lies between 4 and 8 days after the first dithranol challenge.
Circadian Blood Pressure Patterns and Life Stress
Authors: Fallo Francesco , Barzon Luisa , Rabbia Franco , Navarrini Cecilia , Conterno Andrea , Veglio Franco , Cazzaro Manuela , Fava Giovanni A. , Sonino Nicoletta
Published: April 2003

Background: Scarce data are available on the influence of psychological aspects on 24-hour ambulatory blood pressure patterns either in normotensive or hypertensive subjects. This study was designed to evaluate the relationship between psychological profile and changes in daytime/nighttime blood pressure rhythm. Methods:Nocturnal dipping was defined as the night/day ratio of ambulatory mean systolic and/or diastolic blood pressure ≤0.87. Three-hundred and two outpatients (M/F = 174/128; mean age = 49.8 years, SD = 13.6; range, 16–80 years) underwent 24-hour ambulatory blood pressure monitoring. They were administered a self-rating scale, the Psychosocial Index, as an indicator of stress, psychological distress, sleep disturbances, well-being, abnormal illness behavior and quality of life. There were 242 patients taking antihypertensive medication (146 adequately controlled and 96 not controlled) and 60 who were drug free (33 never-treated hypertensive and 27 normotensive subjects). Patients were divided according to the presence (n = 125) or absence (n = 177) of night blood pressure dipping. The two groups were compared using analysis of covariance, with age as a covariate. Results: Dippers had lower (p < 0.001) nocturnal systolic and diastolic blood pressure than nondippers, and higher (p < 0.05) daytime diastolic blood pressure. Patients with nocturnal blood pressure decline had a markedly higher (p < 0.001) level of stress than nondippers. When the sample was divided according to the presence or absence of hypertension, only subjects with normalblood pressure showed nocturnal dipping associated with increased stressful life circumstances. Conclusions: Our findings indicate that dippers experience stressful life circumstances, both in terms of life events and chronic stress. Thissuggests that stress-reducing techniques may be particularly helpful in the setting of hypertension characterized by nighttime blood pressure dipping.
Alterations of Cell Cycle-Regulatory Genes in Prostate Cancer
Authors: Fernández Pedro L. , Hernández Lluis , Farré Xavier , Campo Elías , Cardesa Antonio
Published: April 2003

Deregulated proliferation is one of the main events in neoplastic transformation, and this has prompted increased attention being given to the understanding of the mechanisms involved in cell cycle regulation and its alterations. The ‘retinoblastoma pathway’, a key effector controlling G1-S phase transition, includes several oncogenes and tumour suppressor genes which display a wide range of abnormalities with potential usefulness as markers of evolution or treatment response in prostate cancer. Among these, the existence of p53 mutations seems to predict resistance to radiotherapy or systemic treatment, and p16 overexpression or p27 downregulation seems to serve as markers of poor evolution. The well-established existence of a critical hormonal role in prostate carcinogenesis coupled with the relationship of androgenic activity and regulation of several cell cycle modulators forces cell cycle control in the prostate to be envisioned as a highly complex steroid-influenced system, which will undoubtedly have critical implications in the future management of prostate cancer patients.
A Simple Technique for High-Throughput Screening of Drugs That Modulate Normal and Psoriasis-Like Differentiation in Cultured Human Keratinocytes
Authors: Pol Arno , Bergers Mieke , van Ruissen Fred , Pfundt Rolph , Schalkwijk Joost
Published: April 2003

Established treatments for psoriasis act ei-ther on hyperproliferation, inflammation, aberrant epidermal differentiation or a combination of these aspects of the disease. Potential new drugs for treatment of psoriasis or other disorders with abnormalities in epidermal differentiation can be identified by high-throughput screening of large compound libraries using surrogate markers for the disease. Here we describe a screening model to detect pharmacologically active drugs in two keratinocyte-based, 96-well culture models that use expression of cytokeratin 10 (CK10) and skin-derived antileucoprotease (SKALP)/elafin as markers for normal and psoriatic differentiation, respectively, and allow multiple parameters to be determined from a single well. In this model we tested a number of compounds in a pharmacological range from 10–7 to 10–5 M, including known antipsoriatic drugs, and experimental drugs that are potentially useful in the treatment of psoriasis. All-trans-retinoic acid, dithranol and the p38 mitogen-activated protein (MAP) kinase inhibitor SB220025 displayed a strong inhibitory effect on SKALP expression while cyclosporin A, dexamethasone, the vitamin D3 derivative calcipotriol and the p38 MAP kinase inhibitor SB203580 showed only moderate inhibition. Methotrexate and dimethylfumarate did not affect the expression of SKALP. With respect to CK10 expression, all-trans-retinoic acid, calcipotriol, SB203580 and SB220025 exhibited strong inhibition while dithranol showed only moderate suppression of this normal differentiation marker. Expression levels of CK10 were not significantly affected by dexamethasone, methotrexate, cyclosporin A or dimethylfumarate. This model system parallels most, but not all, findings on the in vitro effect of known antipsoriatic drugs on keratinocytes. In addition, the model identifies p38 MAP kinase inhibitors as potent suppressors of differentiation-associated gene expression. Although further delineation and validation of this model is required, we conclude that the system is amenable to down-scaling and application as a high-throughput screen for differentiation-modifying compounds.
A Rare Case of Metastases to the Maxillary Sinus from Sigmoid Colon Adenocarcinoma
Authors: Cama Elona , Agostino Stefania , Ricci Riccardo , Scarano Emanuele
Published: April 2003

Metastases of malignant tumors to the nasal cavity and paranasal sinuses are rare. A review of the world’s literature reports only four cases of antral metastases from carcinoma of gastrointestinal tract. We present a case of a stenosing adenocarcinoma of the sigmoid colon with metastases within the maxillary sinus. The ENT physical examination revealed a mass involving the right alveolar ridge, the right hard palate. CT scan of the head and the neck showed a large and irregular mass involving the right maxillary sinus, the infratemporal fossa and the pterygoid muscles with resorption of the bone of the posterior portion of the right alveolar ridge and of the posterior wall of the right maxillary sinus. The neoplastic tissue showed marked positivity for CEA and expressed cytokeratin 20, confirming the diagnosis of metastases to the maxillary sinus from colorectal adenocarcinoma. When a differential diagnosis between a second primary tumor of the maxillary sinus and a metastasis has to be carried out, the gastrointestinal tract should be taken into account and detailed immunohistochemical should be performed.
Drugs in the Postsocialist Transitions of Estonia, Latvia, Lithuania and Poland
Authors: Lagerspetz Mikko , Moskalewicz Jacek
Published: April 2003

The article discusses problems related to illicit drugs in Poland, Lithuania, Latvia and Estonia against the background of the postsocialist transitions of the 1990s. Besides the drug problem, the political and market reforms of the 1990s were accompanied by a surfacing of a variety of social problems, some of which had already been present during the authoritarian socialist regimes. Gaining reliable and comparable statistics on drug-related harm has become very difficult due to changes in treatment system and health statistics. Nevertheless, all available evidence suggests that the use of illicit drugs has grown rapidly in all four countries, it now being close to the Western European level. As a result of international impulses rather than domestic interest, strictly restrictive drug policies have been adopted. Drug problems are aggravated by a marginalisation of a large part of the populations. Accordingly, their reduction may require a more general revision of the four countries’ economic and social policies.
Induction of MHC Class II Antigens on Cells of the Inner Ear
Authors: Gloddek Bertrand , Bodmer Daniel , Brors Dominik , Keithley Elizabeth M. , Ryan Allen F.
Published: April 2003

Growing evidence supports the concept that immune reactions occur in the cochlea, where they can function either in protection or as a source of inflammation. Since immunity is generally initiated by antigen presentation of foreign substances to T cells, antigen-presenting cells expressing major histocompatibility complex (MHC) class II molecules are required. Under resting conditions, cochlear cells usually express no MHC class II. However, we show that exposure to γ-interferon in vitro induces an increase in MHC class II expression in neonatal cochlear cells of mice. In addition, MHC class II immunoreactivity was observed in the inner ear of adult mice after induction of sterile labyrinthitis in vivo. It is concluded that the induction of MHC class II molecules by inflammation may render cochlear cells competent to initiate and participate in immune reactions and may therefore contribute to both immunoprotective and immunopathological responses of the inner ear.
Evaluation of Polymerase Chain Reaction for the Detection of Adenoviruses in Conjunctival Swab Specimens Using Degenerate Primers in Comparison with Direct Immunofluorescence
Authors: Weitgasser Ursula , Haller Eva Maria , El-Shabrawi Yosuf
Published: April 2003

Purpose: To investigate a rapid and sensitive polymerase chain reaction (PCR)-based assay for the detection of adenoviral infections in conjunctival swabs. Methods: Degenerate primers derived from the adenoviral hexon gene were designed for amplification of a 302-bp product by PCR. In 15 ocular swab specimens, using a simple sample preparation method, PCR was compared with a commercially available direct immunofluorescence test. Results: Fourteen samples of patients with clinically diagnosed adenoviral keratoconjunctivitis, when screened by direct immunofluorescence, were positive for adenoviral protein. In all samples positive by immunofluorescence, the 302-bp product was amplifiable. The sample negative by direct immunofluorescence was positive using PCR. Conclusion: PCR using degenerate primers proved to have several advantages over current diagnostic techniques. It offers considerable improvement in sensitivity over immunoassays and speed over tissue culture isolation and is a highly potential tool for the diagnosis of adenoviral ocular infections.
Management and Results of Retinal Detachment after Silicone Oil Removal
Authors: Jiang Fagang , Krause Matthias , Ruprecht Klaus W. , Hille Konrad
Published: April 2003

Of the 168 eyes undergoing silicone oil removal from 1993 to 2000, 34 developed retinal detachment after the removal of silicone oil. The management and the results of the 34 eyes were reviewed. Surgical procedures included pars plana vitrectomy, encircling band, cryocoagulation, endotamponade. Five of the 34 eyes had a second retinal detachment after these operations. One of these 5 eyes had a third retinal detachment. Final retinal reattachment was achieved in all eyes. Visual acuity decreased in 16 of the 34 eyes with retinal detachment, and 18 of the 34 eyes had a visual acuity of less than 0.02. These results show that surgery for retinal detachment after silicone oil removal yields a high rate of anatomic success, while the visual outcome is poor for a substantial number of patients.
A Novel Relation of Fatty Acid with Age-Related Macular Degeneration
Authors: Ouchi Masayuki , Ikeda Tsunehiko , Nakamura Kimitoshi , Harino Seiyo , Kinoshita Shigeru
Published: April 2003

To evaluate the relation between fatty acids and age-related macular degeneration (ARMD), the fatty acid fractions within the red blood cell (RBC) membrane and plasma of 11 ARMD patients and 10 healthy individuals (controls) were determined and compared. RBC arachidonic acid (AA) and docosahexaenoic acid (DHA) exhibited significantly higher values in the ARMD patients than in the controls. RBC levels of palmitic, palmitoleic, oleic and linoleic acids, however, showed significantly higher values in the controls than in the ARMD patients. No significant variations were observed between the two groups in terms of plasma levels of AA, DHA, palmitic, palmitoleic, oleic and linoleic acids. Our findings indicate that polyunsaturated fatty acids, vulnerable to free radicals and reactive oxygen species, and easily peroxidized, may be related to ARMD induction.
Subclinically Dry Eyes in Urban Delhi: An Impact of Air Pollution?
Authors: Gupta Suresh K. , Gupta Viney , Joshi Sujata , Tandon Radhika
Published: April 2003

Purpose: To study the effects of air pollution on the eyes of persons staying in the metropolis of New Delhi. Materials and Methods: 400 healthy volunteers from within and outside the metropolis of Delhi were investigated for the presence of tear film abnormalities. All persons underwent slitlamp examination to rule out any ocular surface disorder. The tear break-up time (BUT) was assessed along with a Schirmer test and the tear lysozyme activity and the tear pH were determined. Results: Of the 210 persons staying in the metropolis, 50 (24%) had an abnormal BUT, 14 (6.6%) had an abnormal Schirmer test, and the tear lysozyme activity was found to be low in 12 (5%). In contrast, of those 190 persons living outside the metropolis, only 10 (5.2%) had an abnormal BUT, 4 (2%) had an abnormal Schirmer test, and none had a low lysozyme activity (p < 0.05). None of the persons in either group had significant eye symptoms. Conclusions: Tear film abnormalities are present in a large number of people staying within the metropolis of New Delhi who have apparently normal eyes. Air pollution over a long period of time could possibly be associated with their causation.
RPE in Perfusion Tissue Culture and Its Response to Laser Application
Authors: Framme Carsten , Kobuch Karin , Eckert Elfriede , Monzer Jan , Roider Johann
Published: April 2003

Purpose: To study the effects of conventional laser application on the retinal pigment epithelium (RPE) in a perfusion tissue culture model of porcine retinal pigment epithelium without overlying neurosensory retina. Methods: RPE with underlying choroid was prepared from enucleated porcine eyes and fixed in a holding ring (Minusheet®). Specimens were then placed in two-compartment tissue culture containers (MinuCell & Minutissue, Bad Abbach, Germany) and were cultured during continuous perfusion with culture medium at both sides of the entire specimen, the upper RPE and the lower choroid (12 specimens out of 6 eyes). Cultures were kept for 1, 3, 7 and 14 days and were examined histologically. Laser treatment was performed on each tissue ring by application of 3 × 3 laser burns one day after culture began (argon ion laser, wavelength: 514 nm, pulse duration: 100 ms; spot size: 200 µm) using different energy levels (400–1,000 mW); (16 specimens out of 8 eyes). Results: During laser treatment a marked lightening of the RPE with centrifugal spreading was observed. Using higher levels of energy, a contraction of the RPE towards the center of the laser spot was noticed. One day after laser photocoagulation histology revealed destruction of RPE; within 3–7 days of culture, migration and proliferation of neighboring cells was observed in several lesions. After 7 days the initial defect of the irradiated area was covered with dome shaped RPE cells and after 14 days multilayered RPE cells were showing ongoing proliferation. However, there were also cases without proliferation after laser treatment. The non-treated, continuously perfused RPE showed regular appearance in histological sections: during the first 7 days of culture, light microscopy revealed a normal matrix with a well-differentiated RPE monolayer. Subsequently proliferation even without treatment was observed and after 14 days the RPE became multilayered. Conclusion: It was possible to study the early healing response to the effect of laser treatment using the permanently perfused tissue culture system. A marked proliferation and repair of the laser defect could be observed in several but not all lesions. After 14 days even without laser treatment a proliferative multilayered RPE was present. Although this limits the use of the system for longer than 7 days, it seems to be useful for investigation of RPE-related disorders.
Sex Ratio and Proportion of Affected Sons in Sibships with X-Chromosomal Recessive Traits: Maximum Likelihood Estimation in Truncated Multinomial Distributions
Authors: Fellman Johan , Eriksson Aldur W. , Forsius Henrik
Published: April 2003

If mothers are carriers of a recessive male sex-linked disorder, their children may include females, healthy males and affected males. The composition of the possible sibships follows a multinomial distribution. If the mothers are diagnosed as carriers independently of their offspring, then the distributions are not truncated, but if they are classified as carriers after the birth of at least one affected son, the distributions are truncated. In order to avoid ascertainment bias, the statistical analyses of the corresponding data must differ. We present procedures for estimation in both the untruncated and the truncated case. The formulae obtained are applied to family data for X-chromosomal recessive retinoschisis (RS) from the region of Satakunta in southwestern Finland. Earlier studies indicated that, among the offspring of RS carriers, the sex ratio was increased. In our model, therefore, we include both the proportion of males and the proportion of affected individuals among the males. The sex ratio was significantly increased (131.0), but the proportion of affected males was slightly lower than expected (42.5%). RS seems to be the only known genetic disorder in which the offspring of carriers of the mutation include a statistically significant surplus of males.
How Do Homozygous Parents Affect TDT as a Test for Association?
Authors: Ghosh Saurabh , Reich Theodore
Published: April 2003

The traditional transmission disequilibrium test (TDT) (Spielman et al., 1993) is a powerful test for association only in the presence of linkage. Since allele transmissions from homozygous parents do not carry any information on linkage, the TDT statistic uses data only on heterozygous parents. However, homozygous parents carry information on association between alleles at a marker locus and a disease locus. In this article, we explore whether inclusion of homozygous parents increases the power to detect association. The resultant test statistic follows a χ2 distribution with 2 degrees of freedom. Monte-Carlo simulations are included to compare the performance of this test with the traditional TDT under different disease models.
The Future of Targeted Therapy: Combining Novel Agents
Authors: Gianni Luca
Published: April 2003

The anti-HER2 monoclonal antibody Herceptin® demonstrates significant clinical benefits in patients with HER2-positive metastatic breast cancer (MBC). However, the combination of Herceptin plus anthracyclines, although efficacious, demonstrated a higher than expected incidence of cardiotoxicity. Therefore, studies are currently investigating Herceptin in combination with alternative anthracyclines, such as epirubicin and liposomal doxorubicin. Investigators are also beginning to examine the potential of Herceptin plus hormonal therapy, a combination that will delay the need to use cytotoxic chemotherapy. Furthermore, a plethora of novel agents have been developed that target the processes of tumorigenesis, including HER1 tyrosine-kinase inhibitors, farnesyl-transferase inhibitors, and cyclooxygenase 2 (COX2) inhibitors. Preclinical data demonstrate that the combination of Herceptin with these agents can produce at least additive effects and therefore a rationale exists to investigate these regimens in the clinical setting. As a result of the targeted nature of these agents, it is anticipated that such strategies will have favorable safety profiles. It is possible that through the development and use of biological anticancer agents, such as Herceptin, future anticancer regimens may be specifically tailored to each patient based on their molecular characteristics.
Perspectives on Anti-HER Monoclonal Antibodies
Authors: Ranson Malcolm , Sliwkowski Mark X.
Published: April 2003

The ability of Herceptin® to prolong survival in women with HER2-overexpressing breast tumors has proven the concept of using humanized or chimeric monoclonal antibodies (MAbs) for cancer therapy. MAbs have been developed that are specific for many tumorigenic molecules and receptors. They can potentially be used to treat a range of solid tumors. Among the most promising targets for therapy are members of the human epidermal growth factor receptor (HER/ErbB) family, particularly HER1 and HER2. Several MAbs have been produced that are directed against HER1. One of these agents, cetuximab (Erbitux™), is now advanced in clinical development. HER2 is also a key target and methods are being investigated to maximize the effect of using MAbs to inhibit this receptor. One approach aims to augment the efficacy of trastuzumab (Herceptin) by coupling it to a chemotherapeutic agent, thus enabling the delivery of cytotoxic therapy at a cellular level. Another opportunity is based on research that shows that HER2 acts as a dimerization partner for other HER receptors and consequently is important in HER-ligand-dependent tumor growth. Therefore, anti-HER2 MAbs that inhibit the association of HER2 with other HER family members have the potential to be highly effective. This article reviews some of these alternative approaches to MAb-based anti-HER therapy that will hopefully improve treatment outcome for patients with a range of solid tumors.
Primary Intracerebral Malignant Fibrous Histiocytoma in a Child
Authors: Fujimura Naoko , Sugita Yasuo , Hirohata Masaru , Naohisa Miyagi , Terasaki Mizuhiko , Tokutmi Takashi , Shigemori Minoru
Published: April 2003

We report herein a rare case of pediatric intracerebral malignant fibrous histiocytoma (MFH). A 2-year-old boy gradually developed mild left hemiparesis and became somnolent. Magnetic resonance imaging upon admission revealed a well-enhanced mass lesion in the right frontotemporal operculum. Subtotal removal of the tumor was successfully performed using a right transsulcal and transcortical approach. The tumor developed as an extraaxial mass with brain adhesion to the arterial wall of the branch of the middle cerebral artery rather than to cerebral tissue. Pathological examination confirmed the presence of inflammatory-type MFH. Pediatric cases of intracerebral MFH are rare, and the possible origin of the tumor is discussed based on clinicopathological findings.
The Effectiveness of Hering’s Nerve Stimulation in Controlling Penicillin-Induced Seizures in the Rat Is Dependent on the Amygdala
Authors: Tubbs R. Shane , Wellons III John C. , Patwardhan Ravish V. , Oakes W. Jerry , Wyss J. Michael
Published: April 2003

Objective: This study tests the hypothesis that the ability of Hering’s nerve stimulation (HNS) to blunt seizure activity is dependent on the availability of dopamine in the amygdala. Methods: In 10 rats, Hering’s nerve (HN) on the right side was isolated and placed on an electrode and penicillin was locally placed on each rat’s left frontoparietal region to induce seizures. After the initiation of seizures, HN was stimulated. After the recurrence of seizure activity, the left basolateral amygdala was injected with 1.0 µl of normal saline, dopamine, haloperidol or 1% lidocaine in sequential tests. HN was stimulated after each injection and the latency and amplitude of the seizure activity were assessed. Results: Focal cortical penicillin induced seizures that resulted in tonic-clonic movement of the limbs and face that lasted 35–45 min. Tonic-clonic movements of the limbs and face of similar latency and amplitude were induced by repeated reapplication of penicillin in untreated rats. HNS decreased seizure activity, but infusion of haloperidol or lidocaine into the basolateral amygdala blocked this antiseizure effect of HNS. In contrast, infusion of saline or dopamine had no effect on the ability of HNS to blunt seizure activity. None of the amygdala injections altered the latency or amplitude of seizure activity. Conclusion: These results demonstrate that the ability of HNS to blunt seizure activity in the rat is dependent on an intact dopamine system in the basolateral amygdala. These data will hopefully be useful in furthering our understanding of the circuitry that allows peripheral nerve stimulation to alter seizure activity.
Split Cord Malformation in Two Sisters
Authors: Erşahin Yusuf , Kitiş Ömer , Öner Kazim
Published: April 2003

Split cord malformations (SCMs) are uncommon congenital spinal anomalies and are seen mostly in females. SCMs in siblings are extremely rare. We report two sisters with SCM. These 10- and 8-year-old girls were the first and second children, respectively, of nonconsanguineous parents. Both sisters had a hypertrichosis and pes cavus deformity. The first child had a type I SCM and the second a type II SCM. They had additional spinal lesions, with tethering of the spinal cord. They were operated on and showed an uneventful postoperative course. All reported siblings with SCM have been female. The present data are not sufficient to account for the sex predilection. Therefore, further data and knowledge are needed.
Unique Presentation of Pleomorphic Xanthoastrocytoma as a Lytic Skull Lesion in an Eight-Year-Old Girl
Authors: Jea Andrew , Ragheb John , Morrison Glenn
Published: April 2003

Pleomorphic xanthoastrocytomas (PXAs) are rare primary central nervous system neoplasms of childhood and early adulthood. While PXAs are intimately associated with the leptomeninges, there has never been a description of an extradural-extracranial manifestation of PXA until now. We describe a case of PXA where the patient presented with a calvarial lesion. We also review the differential diagnoses of lytic skull lesions in addition to PXA.
Perimesencephalic Nonaneurysmal Subarachnoid Hemorrhage in the Pediatric Population: Case Report and Review of the Literature
Authors: Anderson Richard C. , Baskin Jonathan , Feldstein Neil A.
Published: April 2003

In approximately 15% of children with atraumatic subarachnoid hemorrhage (SAH), the cause of the hemorrhage cannot be determined despite detailed imaging studies. Perimesencephalic nonaneurysmal subarachnoid hemorrhage (PNSH) is well recognized as a distinct type of SAH in the adult population and may account for up to two thirds of these SAHs of unknown cause. PNSH in the pediatric population, however, is not well recognized. In this report, we confirm the existence of PNSH in the pediatric population by describing a 4-year-old boy who presented with acute SAH in the perimesencephalic cisterns and subsequently had two negative angiograms with a benign clinical course. Recognition of PNSH in the pediatric population is important, especially in view of its benign nature.
Latex Allergy and Sensitization in Children with Spina bifida
Authors: Obojski Andrzej , Chodorski Jacek , Barg Wojciech , Mędrala Wojciech , Fal Andrzej M. , Małolepszy Józef
Published: April 2003

Background: The purpose of this study was to investigate the prevalence rate of latex sensitization and latex allergy among children with spina bifida and to evaluate risk factors for natural rubber latex hypersensitivity. Methods: A total of 34 children between 2.5 and 17 years of age participated in the study. Participants completed a questionnaire and underwent skin prick tests with latex, common aeroallergens and food allergens as well as measurements of specific IgE to latex and food allergens (RAST CAP). Results: The prevalence of latex sensitization and latex allergy was estimated to be 32.4 and 18.8%, respectively. The most common reported clinical manifestation of latex allergy was urticaria. Three out of six symptomatic patients reported anaphylactic reactions. Conclusion: We found that major risk factors for latex sensitization were atopy and a history of numerous operations.
Docetaxel in Combination with Dacarbazine in Patients with Advanced Melanoma
Authors: Bafaloukos D. , Aravantinos G. , Fountzilas G. , Stathopoulos G. , Gogas H. , Samonis G. , Briasoulis E. , Mylonakis N. , Skarlos D.V. , Kosmidis P.
Published: April 2003

Objectives: The number of agents that are active in patients with metastatic melanoma is limited and cure is not a realistic objective for treatment at this stage. The aim of the study was to evaluate the efficacy and safety of new combination regimen cosisting of docetaxel and dacarbazine (DTIC), as first-line chemotherapy, in patients with advanced melanoma. Patients and Methods: Patients with advanced melanoma (including cerebral metastases) were eligible. Docetaxel 80 mg/m2, i.v. over 1 h infusion on day 1, and DTIC 400 mg/m2, i.v. over 45 min on days 1 and 2, were given every 21 days, for six cycles. All patients were premedicated, prior to each course, with methylprednisolone per os. Results: Forty-one patients entered the study. Thirty-nine were assessable for response and 40 for toxicity. Objective responses were seen in 10 patients (24% of the eligible; 95% CI = 12.4–40.3%, 26% of the assessable and 28% of patients with cerebral metastases were excluded). Three of them achieved a complete response (7%; 95% CI = 1.5–19.9) and 7 a partial response (17%; 95% CI = 7.1–32.0), while 8 patients demonstrated stabilization of their disease (20%; 95% CI = 8.8–34.9). After a median follow-up of 20 months, the median time to progression was 7 months (range 0.5–22) and the median survival was 10 months (1–24+). The main toxicity (G3–4) was neutropenia which occurred in 8/40 (20%) patients. Additional patients had reversible G3–4 toxicities including alopecia, nausea and vomiting and fatigue; 3 of them presented mild to moderate hypersensitivity reactions to docetaxel. No toxic death was noted. Conclusions: The combination of docetaxel and DTIC is active and well tolerated in patients with advanced melanoma. While this combination is at least as effective as various combination regimens, it does not differ from that reported for single-agent DTIC.
Human Pharmacokinetic Study of Heated Intraperitoneal Oxaliplatin in Increasingly Hypotonic Solutions after Complete Resection of Peritoneal Carcinomatosis
Authors: Elias D. , El Otmany A. , Bonnay M. , Paci A. , Ducreux M. , Antoun S. , Lasser P. , Laurent S. , Bourget P.
Published: April 2003

Purpose: We studied the pharmacokinetics of heated intraoperative intraperitoneal (i.p.) oxaliplatin (LOHP) solution and its safety profile in increasingly hypotonic solutions. This is the first clinical study of i.p. chemohyperthermia with hypotonic solutions. Methods: Patients with peritoneal carcinomatosis (PC) underwent complete cytoreductive surgery followed by intraoperative i.p. chemohyperthermia (IPCH) with successive dextrose solutions of 300, 200, 150 and 100 mosm/l. LOHP (460 mg/m2) was administered in 2 liters of solution/m2 at an i.p. temperature of 42–44°C for 30 min. IPCH was performed using an open procedure (skin pulled upwards) with a continuous closed circuit. Patients received intravenous leucovorin (20 mg/m2) and 5-fluorouracil (400 mg/m2) just before IPCH to maximize the effect of LOHP. i.p. plasma and tissue samples were analyzed by means of atomic absorption spectrophotometry. Sixteen consecutive patients with PC of either gastrointestinal or peritoneal origin were treated. The safety of the procedure was studied. Results: Pharmacokinetics: The mean duration of the entire procedure was 7.7 ± 2.6 h. Half the LOHP dose was absorbed within 30 min at all dose levels. Absorption was not higher with hypotonic solutions than with isotonic solutions. The area under the curve of LOHP in plasma did not increase with decreasing osmolarity of the i.p. solutions. Intratumoral LOHP penetration was high; it was similar to that at the peritoneal surface, and about 18 times higher than that in nonbathed tissues. LOHP penetration was not significantly increased by using hypotonic solutions. Safety: There was a very high incidence of unexplained postoperative peritoneal bleeding (50%) and unusually severe thrombocytopenia in the 150 and 100 mosm/l groups. Conclusion: Contrary to experimental studies, this clinical study showed no increase in tumoral or systemic penetration of LOHP with i.p. hypotonic solutions (200, 150 or 100 mosm/l) during IPCH. A high incidence of i.p. hemorrhage and thrombocytopenia was observed.
Plasmacytoma of the Cricoid Cartilage with Airway Mass Effect
Authors: O’Neal Michael L. , Entel Robert J.
Published: April 2003

Although multiple myeloma is a common plasma cell dyscrasia, the deposition and organization of these malignant cells in the cricoid cartilage is rare. We report a case of plasmacytoma of the cricoid cartilage and secondary airway obstruction. This important report emphasizes the potential difficulty in diagnosing this condition, consequences of advanced disease, and the importance of combining laryngofissure biopsy and detailed imaging modalities to confirm the diagnosis and guide treatment.
Adolescent Ballet School Students: Their Quest for Body Weight Change
Authors: Bettle Norman , Bettle Oliver , Neumärker Ursula , Neumärker Klaus-Jürgen
Published: April 2003

Body mass index (BMI) and body type of female and male adolescent ballet dancers (n = 90) and school students (n = 156) were determined. Participants were asked for the body weight she or he would prefer, and ballet students were administered the Eating Attitudes Test-40 (EAT-40). Results between age groups and with reference values were compared. Both in dancers and controls, girls wanted to lose more body weight than boys, with female ballet dancers more than female controls. The desire for reducing body weight was expressed by female ballet dancers of all BMI percentiles and body types, with the highest difference between real and desired body weight in 11-, 13-, and 16-year-olds. In the other groups, a quest for lower body weight was expressed only by adolescents of higher BMI and pyknomorphic and/or mesomorphic body type. Female ballet dancers of all age groups sought to reach body weights below the 5th percentile or below 82% of normal body weight. Desired body weight change was influenced by BMI and body type and correlated positively with EAT-40 score.
Iontophoretic Transdermal Delivery of Salicylic Acid Dissolved in Ethanol-Water Mixture in Rats
Authors: Murakami Teruo , Ihara Chie , Kiyonaka Gakuji , Yumoto Ryoko , Shigeki Sadayuki , Ikuta Yushikazu , Yata Noboru
Published: April 2003

The usefulness of iontophoresis is restricted to highly water-soluble compounds, since drugs are generally applied as an aqueous solution in a drug electrode. In the present study, salicylic acid (SA) dissolved in ethanol-water mixture was loaded in a drug electrode, and the effect of ethanol on the iontophoretic transdermal delivery of SA was evaluated. Ethanol at a concentration of 10 or 30% showed no significant effect on the iontophoretic transdermal delivery of SA compared to that in the absence of ethanol, but 40 or 70% ethanol increased it significantly. The current density passing through in vivo during iontophoretic treatment decreased with increase in ethanol concentrations. These results suggested that the enhanced transdermal absorption of SA iontophoretically by the presence of ethanol in a drug solution is not due to the increased current density in vivo, but probably due to the direct action of ethanol on the stratum corneum. In conclusion, addition of ethanol to a drug solution at an appropriate concentration was proved to enhance the iontophoretic transdermal delivery of SA. A mixture of ethanol and water can dissolve many poorly water-soluble drugs, and therefore it would be able to expand the application of iontophoresis to include many drugs that are poorly soluble in water.
Long-Term Stability of 8-Methoxypsoralen in Ointments for Topical PUVA Therapy (‘Cream-PUVA’)
Authors: Martens-Lobenhoffer J. , Rinke M. , Lösche D. , Gollnick H.
Published: April 2003

8-Methoxypsoralen (8-MOP) is an established photochemotherapeutic agent for PUVA therapy. Recently, a so-called ‘cream-PUVA’ modality was introduced into therapy of psoriasis and other dermatoses. Little is known, however, about the stability of 8-MOP in ointments used for the topical application of this compound. Therefore, we investigated the long-term stability of 8-MOP in three different ointments, Unguentum CordesTM, Cold Cream NaturelTM and a water-containing gel on the basis of Carbopol 940. All three ointments were prepared with 8-MOP concentrations of 0.05 and 0.005%, and stored over 12 weeks at room temperature (19–20°C) and at 5°C. 8-MOP concentrations were measured at days 1, 8, 15, 29, 57 and 88 after preparation by thin-layer chromatography (TLC). The ointments were dissolved in an organic solvent, 10 µl were transferred onto the TLC plate and the chromatograms were developed first in toluene and then in toluene/ethyl acetate 2:1 v/v to resolve 8-MOP from the ointment constituents. The peak heights of 8-MOP were used for quantitation. The intraday variabilities are <3% for Unguentum Cordes and Cold Cream Naturel and <6% for the Carbopol 940 gel. The interday variabilities were <6.3% in all cases. In Unguentum Cordes and Cold Cream Naturel the concentrations of 8-MOP remain stable, but in Unguentum Cordes the emulsion began to break up after 8 weeks. In the Carbopol gel, only about 40% of the nominal concentrations of 8-MOP were found and they decrease significantly at storage at 5°C. We conclude that the Carbopol gel seems to be unsuitable for PUVA therapy, whereas Cold Cream Naturel shows the best results.