bluuebunny/crossref_metadata_2025 huggingface dataset:
Geographic variation in snapping turtle (Chelydra serpentina serpentina) egg components across a longitudinal transect
Authors: Finkler Michael S , Steyermark Anthony C , Jenks Kate E
Published: April 2004

Common snapping turtles (Chelydra serpentina serpentina) have an extensive range across North America, inhabiting aquatic habitats in diverse thermal and hydric climates. Although geographic variation in reproductive characters such as female size, clutch size, and egg mass have been investigated, little is known about geographic variation in egg components. In this study, we examined variation in the water content, solid content, and shell mass of snapping turtle eggs from four populations dispersed along a longitudinal geographic transect (Pennsylvania, Michigan, Minnesota, and Nebraska). Initial egg mass and dry shell mass were similar among these four populations. However, water contents of eggs correlated positively with longitude, whereas dry content mass correlated negatively with longitude. Moreover, water content of eggs correlated negatively with the average number of days per year where average air temperatures exceeded 15 °C in a particular region (an indicator of regional thermal climate), and dry content of eggs correlated positively with both the number of days per year where average air temperatures exceeded 15 °C and the average total precipitation for the months of May through September (an indicator of regional hydric climate). These findings suggest that egg content (and perhaps egg quality) in this wide-ranging species of turtle varies in a manner reflecting differences in climate.
ORGANISATIONAL RESPONSES TO DISCONTINUOUS INNOVATION: A CASE STUDY APPROACH
Authors: MACHER JEFFREY T. , RICHMAN BARAK D.
Published: April 2004

Research that examines entrant-incumbent dynamics often points to the organisational limitations that constrain incumbents from successfully pursuing new technologies or fending off new entrants. Some incumbents are nevertheless able to successfully implement organisational structures and develop routines that overcome these institutional constraints. We provide a case-study analysis of how three firms — Motorola, IBM and Kodak — responded to "discontinuous" innovations and the associated structural and organisational limitations that are typical to incumbent organisations. Each firm was able to capture gains from new technologies and develop profitable products in emerging markets, although their abilities to sustain these gains varied due to subsequent organisational changes. Drawing from these case studies, we synthesise how firms can institute organisational strategies to continue to capture gains from disruptive innovations. A schema suggests that particular organisational strategies are comparatively optimal for corresponding points along an innovation lifecycle.
CONTINGENT CAPABILITIES AND THE PROCUREMENT OF COMPLEX PRODUCT SYSTEMS
Authors: FLOWERS STEPHEN
Published: April 2004

This paper focuses on how organisations utilise external capabilities to procure high-technology products and services. It is argued that the conceptual frameworks developed in the context of organisations which manufacture such products need to be modified to explain the behaviour of organisations that buy them. The use of third-party consultants in the procurement process is explored and a new class of temporary capabilities, termed Contingent Capabilities, is proposed. This class of capabilities occupies the boundary between accepted notions of core and non-core, and play an essential role in the innovation process. The roles of two distinct categories of Contingent Capabilities, strategic and tactical, within the innovation process are explored. The paper concludes with an agenda for further work in this area.
Role of mitochondrial superoxide dismutase in contraction-induced generation of reactive oxygen species in skeletal muscle extracellular space
Authors: McArdle A. , van der Meulen J. , Close G. L. , Pattwell D. , Van Remmen H. , Huang T. T. , Richardson A. G. , Epstein C. J. , Faulkner J. A. , Jackson M. J.
Published: April 2004

Contractions of skeletal muscles produce increases in concentrations of superoxide anions and activity of hydroxyl radicals in the extracellular space. The sources of these reactive oxygen species are not clear. We tested the hypothesis that, after a demanding isometric contraction protocol, the major source of superoxide and hydroxyl radical activity in the extracellular space of muscles is mitochondrial generation of superoxide anions and that, with a reduction in MnSOD activity, concentration of superoxide anions in the extracellular space is unchanged but concentration of hydroxyl radicals is decreased. For gastrocnemius muscles from adult (6–8 mo old) wild-type ( Sod2+/+) mice and knockout mice heterozygous for the MnSOD gene ( Sod2+/-), concentrations of superoxide anions and hydroxyl radical activity were measured in the extracellular space by microdialysis. A 15-min protocol of 180 isometric contractions induced a rapid, equivalent increase in reduction of cytochrome c as an index of superoxide anion concentrations in the extracellular space of Sod2+/+ and Sod2+/- mice, whereas hydroxyl radical activity measured by formation of 2,3-dihydroxybenzoate from salicylate increased only in the extracellular space of muscles of Sod2+/+ mice. The lack of a difference in increase in superoxide anion concentration in the extracellular space of Sod2+/+ and Sod2+/- mice after the contraction protocol supported the hypothesis that superoxide anions were not directly derived from mitochondria. In contrast, the data obtained suggest that the increase in hydroxyl radical concentration in the extracellular space of muscles from wild-type mice after the contraction protocol most likely results from degradation of hydrogen peroxide generated by MnSOD activity.
Identification of stathmin as a novel marker of cell proliferation in the recovery phase of acute ischemic renal failure
Authors: Zahedi Kamyar , Wang Zhaohui , Barone Sharon , Tehrani Kathy , Yokota Naoko , Petrovic Snezana , Rabb Hamid , Soleimani Manoocher
Published: April 2004

Ischemic renal injury can be classified into the initiation and extension phase followed by the recovery phase. The recovery phase is characterized by increased dedifferentiated and mitotic cells in the damaged tubules. Suppression subtractive hybridization was performed by using RNA from normal and ischemic kidneys to identify the genes involved in the physiological response to ischemia-reperfusion injury (IRI). The expression of stathmin mRNA increased by fourfold at 24 h of reperfusion. The stathmin mRNA did not increase in sodium-depleted animals or in animals with active, persistent injury secondary to cis-platinum. Immunofluorescent labeling demonstrated that the expression of stathmin increased dramatically at 48 h of reperfusion. Labeling with antibodies to stathmin and proliferating cell nuclear antigen (PCNA) indicates that the expression of stathmin was induced before the upregulation of PCNA and that all PCNA-positive cells expressed stathmin. Double immunofluorescent labeling demonstrated the colocalization of stathmin with vimentin, a marker of dedifferentiated cells. Stathmin expression was also significantly enhanced in acute tubular necrosis in humans. On the basis of its induction profile in IRI, the data indicating its enhanced expression in proliferating cells and regenerating organs, we propose that stathmin is a marker of dedifferentiated, mitotically active epithelial cells that may contribute to tubular regeneration and could prove useful in distinguishing the injury phase from recovery phase in IRI.
Contribution of oxygen radicals to altered NO-dependent pulmonary vasodilation in acute and chronic hypoxia
Authors: Jernigan Nikki L. , Resta Thomas C. , Walker Benjimen R.
Published: April 2004

Chronic hypoxia (CH) increases pulmonary arterial endothelial nitric oxide (NO) synthase (NOS) expression and augments endothelium-derived nitric oxide (EDNO)-dependent vasodilation, whereas vasodilatory responses to exogenous NO are attenuated in CH rat lungs. We hypothesized that reactive oxygen species (ROS) inhibit NO-dependent pulmonary vasodilation following CH. To test this hypothesis, we examined responses to the EDNO-dependent vasodilator endothelin-1 (ET-1) and the NO donor S-nitroso- N-acetyl penicillamine (SNAP) in isolated lungs from control and CH rats in the presence or absence of ROS scavengers under normoxic or hypoxic ventilation. NOS was inhibited in lungs used for SNAP experiments to eliminate influences of endogenously produced NO. Additionally, dichlorofluorescein (DCF) fluorescence was measured as an index of ROS levels in isolated pressurized small pulmonary arteries from each group. We found that acute hypoxia increased DCF fluorescence and attenuated vasodilatory responses to ET-1 in lungs from control rats. The addition of ROS scavengers augmented ET-1-induced vasodilation in lungs from both groups during hypoxic ventilation. In contrast, upon NOS inhibition, DCF fluorescence was elevated and SNAP-induced vasodilation diminished in arteries from CH rats during normoxia, whereas acute hypoxia decreased DCF fluorescence, which correlated with augmented reactivity to SNAP in both groups. ROS scavengers enhanced SNAP-induced vasodilation in normoxia-ventilated lungs from CH rats similar to effects of hypoxic ventilation. We conclude that inhibition of NOS during normoxia leads to greater ROS generation in lungs from both control and CH rats. Furthermore, NOS inhibition reveals an effect of acute hypoxia to diminish ROS levels and augment NO-mediated pulmonary vasodilation.
Mechanisms of organophosphate insecticide-induced airway hyperreactivity
Authors: Fryer Allison D. , Lein Pamela J. , Howard Angela S. , Yost Bethany L. , Beckles Rondell A. , Jett David A.
Published: April 2004

It has been suggested that pesticide exposure may be a contributing factor underlying the increased incidence of asthma in the United States and other industrialized nations. To test this hypothesis, airway hyperreactivity was measured in guinea pigs exposed to chlorpyrifos, a widely used organophosphate pesticide. Electrical stimulation of the vagus nerves caused frequency-dependent bronchoconstriction that was significantly potentiated in animals 24 h or 7 days after a single subcutaneous injection of either 390 mg/kg or 70 mg/kg of chlorpyrifos, respectively. Mechanisms by which chlorpyrifos may cause airway hyperreactivity include inhibition of acetylcholinesterase (AChE) or dysfunction of M3 muscarinic receptors on airway smooth muscle or of autoinhibitory M2 muscarinic receptors on parasympathetic nerves in the lung. AChE activity in the lung was significantly inhibited 24 h after treatment with 390 mg/kg of chlorpyrifos, but not 7 days after injection of 70 mg/kg of chlorpyrifos. Acute exposure to eserine (250 μg/ml) also significantly inhibited lung AChE but did not potentiate vagally induced bronchoconstriction. Neuronal M2 receptor function was tested using the M2 agonist pilocarpine, which inhibits vagally induced bronchoconstriction in control animals. In chlorpyrifos-treated animals, pilocarpine dose-response curves were shifted significantly to the right, demonstrating decreased responsiveness of neuronal M2 receptors. In contrast, chlorpyrifos treatment did not alter methacholine-induced bronchoconstriction, suggesting that chlorpyrifos does not alter M3 muscarinic receptor function on airway smooth muscle. These data demonstrate that organophosphate insecticides can cause airway hyperreactivity in the absence of AChE inhibition by decreasing neuronal M2 receptor function.
Transgenic smooth muscle expression of the human CysLT1receptor induces enhanced responsiveness of murine airways to leukotriene D4
Authors: Yang Guochang , Haczku Angela , Chen Hang , Martin Viviane , Galczenski Helen , Tomer Yaniv , Van Beisen Christopher R. , Evans Jilly F. , Panettieri Reynold A. , Funk Colin D.
Published: April 2004

Cysteinyl leukotrienes (CysLTs) exert potent proinflammatory actions and contribute to many of the symptoms of asthma. Using a model of allergic sensitization and airway challenge with Aspergillus fumigatus ( Af), we have found that Th2-type inflammation and airway hyperresponsiveness (AHR) to methacholine (MCh) were associated with increased LTD4responsiveness in mice. To explore the importance of increased CysLT signaling in airway smooth muscle function, we generated transgenic mice that overexpress the human CysLT1 receptor (hCysLT1R) via the α-actin promoter. These receptors were expressed abundantly and induced intracellular calcium mobilization in airway smooth muscle cells from transgenic mice. Force generation in tracheal ring preparations ex vivo and airway reactivity in vivo in response to LTD4were greatly amplified in hCysLT1R-overexpressing mice, indicating that the enhanced signaling induces coordinated functional changes of the intact airway smooth muscle. The increase of AHR imposed by overexpression of the hCysLT1R was greater in transgenic BALB/c mice than in transgenic B6 × SJL mice. In addition, sensitization- and challenge-induced increases in airway responsiveness were significantly greater in transgenic mice than that of nontransgenic mice compared with their respective nonsensitized controls. The amplified AHR in sensitized transgenic mice was not due to an enhanced airway inflammation and was not associated with similar enhancement in MCh responsiveness. These results indicate that a selective hCysLT1R-induced contractile mechanism synergizes with allergic AHR. We speculate that hCysLT1R signaling contributes to a hypercontractile state of the airway smooth muscle.
Autoinhibitory domain fragment of endothelial NOS enhances pulmonary artery vasorelaxation by the NO-cGMP pathway
Authors: Hu Hanbo , Xin Meiguo , Belayev Leonid L. , Zhang Jianliang , Block Edward R. , Patel Jawaharlal M.
Published: April 2004

Catalytic activity of eNOS is regulated by multiple posttranscriptional mechanisms, including a 40-amino acid (604-643) autoinhibitory domain (AID) located in the reductase domain of the eNOS protein. We examined whether an exogenous synthetic AID, an 11-amino acid (626-636) fragment of AID (AAF), or scrambled AAF (AAF-SR), enhanced eNOS activity and NO-cGMP-mediated vasorelaxation using pulmonary artery (PA) endothelial/smooth muscle cell (PAEC/PASM) coculture, isolated PA segment, and isolated lung perfusion models. Incubation of isolated total membrane fraction of PAEC with AID or AAF resulted in concentration-dependent loss of eNOS activity. In contrast, incubation of intact PAEC with AID or AAF but not AAF-SR caused concentration- and time-dependent activation of eNOS. Because AID and AAF had similar effects on activation of eNOS, AAF and AAF-SR were used for further evaluation. Although AAF stimulation increased catalytic activity of PKC-α in PAEC, AAF-mediated activation of eNOS was independent of phosphorylation of Ser1177 or Thr495 and/or expression of eNOS protein. AAF stimulation of PAEC increased NO and cGMP production, which were attenuated by pretreatment with the eNOS inhibitor l-NAME. AAF caused time-dependent vasodilation of U-46619-precontracted endothelium-intact but not endothelium-denuded PA segments, and this response was attenuated by l-NAME. AAF, but not AAF-SR, also caused vasorelaxation in an ex vivo isolated mouse lung perfusion model precontracted with U-46619. Incubation with fluorescence-labeled AAF demonstrated translocation of AAF in PAEC in culture, isolated PA, and isolated intact lungs. These results demonstrate that AAF-stimulated vasodilation is mediated via activation of eNOS and enhanced NO-cGMP production in PA and intact lung.
Evidence for the Involvement of Protein Kinase C in Acidic pH-Induced Contraction in Spontaneously Hypertensive Rat Aorta
Authors: Rohra Dileep Kumar , Yamakuni Tohru , Ito Saiko , Saito Shin-ya , Ohizumi Yasushi
Published: April 2004

This study was performed to test the hypothesis that activation of protein kinase C (PKC) is a mechanism underlying the acidic pH-induced contraction (APIC) in spontaneously hypertensive rat (SHR) aorta. Changing pH of the bathing solution from 7.4 to 6.5 induced a marked contraction of SHR aorta. PKC inhibitors, GF109203X and calphostin C markedly inhibited the APIC selectively, without having a marked effect on the KCl-induced contraction. Inhibitors of mitogen-activated protein kinase kinase, U0126 and PD98059 mildly but significantly attenuated the APIC. However, at the similar concentrations both U0126 and PD98059 inhibited the KCl-induced contraction in a manner similar to that observed in APIC. D-609, an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC) markedly inhibited the APIC and the extent of inhibition by this compound was similar to that shown by PKC inhibitors. Whereas, U-73122 and propranolol, inhibitors of phosphatidylinositol-specific PLC and phosphatidate phosphohydrolase, respectively, had no affect on the APIC. A tyrosine kinase inhibitor, tyrphostin 23 and GF109203X inhibited the APIC in an additive manner, and together they abolished the contractile response. From all these results, it is suggested that a significant component of the contraction observed in response to acidosis in SHR aorta is dependent upon the activation of PKC that seems to be the downstream event of the activation of PC-PLC. Furthermore, PKC- and tyrosine kinase-dependent pathways underlying the APIC are independent of each other.
DY-9760e, a Novel Calmodulin Antagonist, Reduces Infarction after Permanent Focal Cerebral Ischemia in Rats
Authors: Sato Toshiyuki , Takamori Hideo , Shirasaki Yasufumi
Published: April 2004

DY-9760e (3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate), a novel calmodulin antagonist, provides effective protection against Ca2+ ionophore-induced cytotoxicity and brain injury induced by transient focal ischemia. In this study, we evaluated the effect of DY-9760e on ischemic infarct volume in rats subjected to permanent focal ischemia. DY-9760e (0.5 mg/kg/h for 6 h) significantly reduced the infarct volume when administered immediately after middle cerebral artery occlusion. Furthermore, this neuroprotection was also exerted by treatment with a 3-hour delay, implying that the therapeutic time window for this compound is at least 3 h. In addition, although treatment with 0.1 mg/kg/h for 24 h was ineffective, the combination of a loading dose of 0.3 mg/kg/h for 2 h followed by 0.1 mg/kg/h for 22 h yielded a significant reduction in infarct volume. Thus, prolonged infusion preceded by a loading dose is an efficacious dosing regimen for DY-9760e, especially at a low infusion rate. These data demonstrate the substantial neuroprotective effect of DY-9760e in a permanent focal ischemia model and indicate that this neuroprotectant may be of therapeutic value for the treatment of acute stroke.
SAG1 Is a Host-Targeted Antigen for Protection against Toxoplasma gondii Infection
Authors: Seng S. , Makala L.H.C. , Yokoyama M. , Lim C. , Choi Y.H. , Suzuki N. , Toyoda Y. , Nagasawa H.
Published: April 2004

We previously reported that SAG1 transgenic (tg) mice have an elevated susceptibility resulting from their inability to elicit strong Th1-based protection against Toxoplasma gondii infection. Here, we demonstrate that SAG1 tg mice were protected against T. gondii infection, characterized by a decline in IFN-γ levels, following administration of a lethal dose of T. gondii. Moreover, immunization with T. gondii homogenate conferred protection and induced production of IgG, with IgG1 and IgG2a subclasses driven by Th2 and Th1 responses, respectively, in both SAG1 tg and wild-type (wt) mice. IgG titers were significantly higher from day 10 after immunization in wt mice compared to those in SAG1 tg mice. There were no significant differences observed in levels of IgG1 in both groups. However, significantly lower IgG2a titers were measured in the sera from SAG1 tg mice on days 10, 15 and 20. IFN-γ levels in sera were significantly lower in SAG1 tg mice compared to those in wt mice on day 20 after immunization. When challenged with a lethal dose of the Beverley strain of T. gondii, 80 and 100% survival rates were observed in SAG1 tg and wt mice, respectively, indicating that SAG1 tg mice were protected to a lesser extent from challenge due to the decrease in protective immunity. These results suggest that SAG1 plays a critical role in eliciting protection, hence a target antigen for the development of protective Th1-based responses against T. gondii infection in mice.
Etiology and Management of Seborrheic Dermatitis
Authors: Gupta Aditya K. , Madzia S.E. , Batra Roma
Published: April 2004

Seborrheic dermatitis (SD) is a common dermatological disorder that varies greatly in severity between individuals and with time. The etiology of this disease is poorly understood. Early investigators focused on the role of Malassezia (previously Pityrosporum) yeasts in the development of SD. Some researchers have hypothesized that there is an immunological component to SD and that this disease is caused by an altered immune response to Malassezia yeasts. However, other researchers view this condition as the result of hyperproliferation. Both antifungal and anti-inflammatory preparations have been used to treat SD effectively and safely. The wide range of antifungal formulations available (creams, shampoos, oral drugs) provides safe, effective and flexible treatment options for SD.
Determining the Mechanical Properties of Rat Skin with Digital Image Speckle Correlation
Authors: Guan E. , Smilow Sarah , Rafailovich Miriam , Sokolov Jonathan
Published: April 2004

Background: Accurate measurement of the mechanical properties of skin has numerous implications in surgical repair, dermal disorders and the diagnosis and treatment of trauma to the skin. Investigation of facial wrinkle formation, as well as research in the areas of skin aging and cosmetic product assessment can also benefit from alternative methodologies for the measurement of mechanical properties. Objective: A noncontact, noninvasive technique, digital image speckle correlation (DISC), has been successfully introduced to measure the deformation field of a skin sample loaded by a material test machine. With the force information obtained from the loading device, the mechanical properties of the skin, such as Young’s modulus, linear limitation and material strength, can be calculated using elastic or viscoelastic theory. Methods: The DISC method was used to measure the deformation of neonatal rat skin, with and without a glycerin-fruit-oil-based cream under uniaxial tension. Results: Deformation to failure procedure of newborn rat skin was recorded and analyzed. Single skin layer failures were observed and located by finding the strain concentration. Young’s moduli of freshly excised rat skin, cream-processed rat skin and unprocessed rat skin, 24 h after excision, were found with tensile tests to be 1.6, 1.4 and 0.7 MPa, respectively. Conclusion: Our results have shown that DISC provides a novel technique for numerous applications in dermatology and reconstructive surgeries.
Review of 120 Biopsies Performed on the Balanopreputial Sac
Authors: Alessi Elvio , Coggi Antonella , Gianotti Raffaele
Published: April 2004

Background: Long-lasting erythematous lesions involving the balanopreputial sac may be clinically difficult to classify, and biopsies may be performed in order to clarify the nature of the disease. However, our previous experience led us to consider several cases as histopathologically unclassifiable. Objective: To establish the causes of such unsatisfactory findings. Methods: We reviewed 120 balanopreputial sac biopsies performed at the surgical unit of our institute from January 1999 to December 2002 examining also the patients’ clinical records. Results: We found that a small group of previously unclassified cases showed common clinical and histopathological features. Clinically, all patients were uncircumcised and had long-lasting asymptomatic erythematous plaques on the balanopreputial sac with no erythroplastic or lichenoid features and no correlation with sexual intercourse. Histologically, all specimens showed a thinned and spongiotic epithelium, a band-like infiltrate of lymphocytes and histiocytes with a variable number of plasma cells in the upper part of the chorion and further signs of acute, subacute or chronic inflammation. Conclusions: In our view, these cases fall within a spectrum of inflammatory non-cicatricial disorders, ranging from almost pure lymphohistiocytic forms to forms which fulfil all criteria to be classified as balanitis circumscripta plasmacellularis of Zoon. We propose to classify these cases histologically as inflammatory non-cicatricial balanoposthitis and clinically as idiopathic inflammatory non-cicatricial balanoposthitis.
Role of Laser Therapy in Dermatology – Clinical Aspects
Authors: Landthaler M. , Ulrich H. , Hohenleutner S. , Wimmershoff M. , Hohenleutner U.
Published: April 2004

Background: Laser therapy has become an integral part of therapeutic alternatives in dermatology. Nevertheless, there are only few statistical data on the role of lasers in everyday practice of dermatological clinics. Objective: Analysis of laser patients, indications and lasers used. Methods: We analysed 10,244 patients treated with laser therapy in the Department of Dermatology at the University of Regensburg from 1992 to 2000. This figure represents 9.6 % of all patients seen during that period. Results: Vascular lesions (hemangiomas, port-wine stains, telangiectasias) represented the most common indication (more than 70%) followed by infectious disorders (mostly papillomavirus lesions) as well as the removal of hairs and tattoos. Accordingly, the most frequently used laser was the flashlamp-pumped pulsed dye laser (585 nm) followed by the argon ion, the long-pulse tunable flashlamp-pumped pulsed dye laser, the Q-switch ruby laser, and the CO2-laser. In recent years, the percentage of indications and lasers used has changed significantly, reflecting the development of new lasers and the introduction of new indications. Conclusions: The results confirm the important role of laser therapy in dermatology.
Congenital Self-Healing Reticulohistiocytosis Mimicking Diffuse Neonatal Hemangiomatosis
Authors: Huang Ching-Yuang , Chao Sheau-Chiou , Ho Shae-Fang , Lee Julia Yu-Yun
Published: April 2004

Congenital self-healing reticulohistiocytosis (CSRH), a rare benign variant of Langerhans cell histiocytosis (LCH), is characterized by (a) congenital skin lesions, (b) a healthy infant with no systemic involvement, (c) the histopathologic finding of a Langerhans cell infiltrate and (d) spontaneous involution within the first year of life without sequelae. We report a Taiwanese girl born with widespread hemangioma-like lesions. The diagnosis of LCH was confirmed by finding a diffuse dermal infiltrate of S-100-protein- and OKT6 (CD1a)-positive mononuclear cells and the presence of Birbeck granules in 10% of the mononuclear cells ultrastructurally. The diagnosis of CSRH was further established by rapid and complete involution of the lesions in 3 months. No recurrence was noted for 7 years. Our case illustrates that CSRH can mimic diffuse neonatal hemangiomatosis clinically; thus, it is important to include CSRH in the differential diagnosis of congenital or neonatal hemangiomatosis.
Primary Vulvar Melanoma with Satellite Metastasis: Dermoscopic Findings
Authors: Virgili Annarosa , Zampino Maria Rosaria , Corazza Monica
Published: April 2004

A 79-year-old woman presented with a 1-year history of a pigmented nodular lesion on the left labium minor. Histopathology of the nodule led to a diagnosis of metastatic melanoma. A pigmented flat lesion on the inner side of the left labium major was also biopsied and was found to be a superficial spreading melanoma. The dermoscopic findings of primary and metastatic vulvar melanoma which simultaneously occurred in the same patient are described. Dermoscopy revealed a homogeneous pattern associated with linear irregular vessels in the metastatic nodule, while irregular globules and streaks were seen in the primary melanoma.
Xanthoma disseminatum with Large Plaques Confined to the Back, Pulmonary Involvement and Multiple Intestinal Xanthomas
Authors: Hisanaga Y. , Akaike Y. , Kuroda K.
Published: April 2004

Xanthoma disseminatum (XD) is a rare benign mucocutaneous xanthomatosis that is classified as a benign non-Langerhans cell histiocytosis. We report a 68-year-old man who presented with peculiar, large plaques confined to the back 7 years after the onset of cranial diabetes insipidus. Histopathological features of the cutaneous lesions were typical of XD. The patient had lower respiratory tract involvement with histiocytic infiltrates, which was unresponsive to various treatments and resulted in a fatal outcome. Gastrointestinal endoscopies revealed multiple xanthomas in the sigmoid colon and the rectum. To our knowledge, this is the first reported case of intestinal xanthomas associated with XD.
Mycosis fungoides Progression and Chronic Solvent Exposure
Authors: Nikkels Arjen F. , Quatresooz Pascale , Delvenne Philippe , Balsat Alain , Piérard Gérald E.
Published: April 2004

The effect of repeated exposure to specific chemicals on the initiation or progression of mycosis fungoides (MF) remains unsettled. A patient with low-grade patch stage MF progressively developed MF plaques restricted to his arms, and a tumour on his right thigh. These areas were subject to repeated exposure to solvents. His thigh was indeed in close contact with his trousers pocket where he used to store a wiping rag drenched into white spirit and cellulosic thinner. Immunophenotyping these lesions revealed a dense LCA+, CD2+, CD3+, CD4+, CD5+, CD7+, CD45+, CD45RO+ T-cell infiltrate admixed with many factor XIIIa+ dendrocytes. T-cell receptor rearrangement analysis identified a monoclonal T-cell infiltrate. An internal work-up remained negative. Stopping further solvent exposure failed to improve his condition. Oral corticotherapy combined with low-dose interferon-α2a halted disease progression. This observation suggests that long-term solvent exposure may trigger MF and hasten its progression from the patch stage to the plaque and tumour stages.
Selective Termination for Fetal Anomaly/Genetic Disorder in Twin Pregnancy at 32+ Menstrual Weeks
Authors: Hern Warren M.
Published: April 2004

Objectives: To conduct a pilot study of 4 cases of selective termination of a single abnormal fetus in a dichorionic, diamniotic twin pregnancy advanced to 32 or more menstrual weeks of gestation. Study Design: This is a case series of 4 patients in highly unusual circumstances and treatment. Four healthy patients with desired pregnancies complicated by the presence of an abnormal genetic or developmental diagnosis in 1 twin were treated by selective termination of the abnormal twin using intracardiac injection of potassium chloride. Results: In all 4 patients, cardiac arrest in the abnormal twin was effected without disturbance of the healthy twin or the mother. Postoperative maternal serum potassium levels remained at normal levels. Delivery of a healthy surviving twin occurred from 2 days to 4 weeks following the selective termination along with delivery of a stillborn abnormal twin. Conclusion: Selective termination of an abnormal twin may be performed on an outpatient basis in the last weeks of pregnancy.
Nodular Glomerulosclerosis in Cystic Fibrosis Mimics Diabetic Nephropathy
Authors: Westall Glen P. , Binder John , Kotsimbos Tom , Topliss Duncan , Thomson Napier , Dowling John , Wilson John W.
Published: April 2004

Background/Aims: Despite the cystic fibrosis gene product, the cystic fibrosis transmembrane conductance regulator, being widely expressed throughout the kidney, there is no clearly defined renal phenotype in patients with cystic fibrosis. As patients with cystic fibrosis survive longer progressive pancreatic destruction may lead to abnormal glucose tolerance and diabetes mellitus, which in the kidney may be associated with the characteristic changes of nodular glomerulosclerosis. Methods: The adult cystic fibrosis service at the Alfred hospital consists of a cohort of 200 patients. We describe 3 cystic fibrosis patients with impaired renal function who had renal biopsies performed as part of their diagnostic work-up. All patients had fasting plasma glucose levels, oral glucose tolerance tests and measurements of HbA1c performed to assess for the presence of cystic fibrosis-related diabetes mellitus. Results: The renal biopsies of all 3 patients showed histological changes characteristic of diabetic nephropathy. In all cases described characteristic Kimmelstiel-Wilson nodules were present. However, in all 3 patients the presence of impaired glucose tolerance and diabetes mellitus was excluded using standard biochemical diagnostic criteria. Conclusion: We describe 3 adult CF patients, who on renal biopsy had histological evidence of nodular glomerulosclerosis in the absence of abnormal glucose metabolism. We speculate that the pro-inflammatory cytokine profile, typical of cystic fibrosis, predisposes to the lesions described.
Evaluation of Methods to Detect and Characterize Antibodies against Recombinant Human Erythropoietin
Authors: Swanson Steven J. , Ferbas John , Mayeux Patrick , Casadevall Nicole
Published: April 2004

Background: From May 1998 to November 2000, 13 European patients developed antibody-mediated pure red cell aplasia during treatment with recombinant human erythropoietin (rHuEPO), reinforcing the need for analytical testing for antibodies against erythropoietic agents. Specimens from 8 patients were provided for further antibody testing and characterization. Methods: We evaluated 4 analytical methods with these sera: radioimmune precipitation (RIP), enzyme-linked immunosorbent assay (ELISA), biosensor immunoassay, and a bioassay for identification of neutralizing antibodies. Results: The RIP, biosensor immunoassay, and biological assay performed equally to detect and quantify anti-rHuEPO antibodies. The ELISA failed to detect antibodies in 2 patient samples. The biosensor immunoassay could determine antibody isotypes, subclasses, and dissociation rates and the bioassay could determine whether these antibodies were able to neutralize the biological effect of the drug; the other assays could not make this determination. Conclusion: We recommend the use of the biosensor immunoassay followed by a bioassay to best identify and characterize anti-rHuEPO antibodies. The biosensor immunoassay allows for identification of all classes and subclasses of immunoglobulins and is a preferred method for the identification of lower-affinity antibodies. The bioassay is needed to determine if the antibodies identified have the capacity to neutralize a biological effect of the drug in a cell-based system.
Tubular and Interstitial Cell Apoptosis in the Streptozotocin-Diabetic Rat Kidney
Authors: Kumar Dinender , Zimpelmann Joseph , Robertson Susan , Burns Kevin D.
Published: April 2004

Background/Aims: Angiotensin II (Ang II) mediates progressive nephron loss in diabetes and stimulates apoptotic cell death in several tissues. We studied the extent of apoptosis in streptozotocin (STZ) induced diabetic nephropathy in the rat and the effects of insulin and type 1 (AT1) or type 2 (AT2) Ang II receptor blockade with losartan or PD123319, respectively. Methods: Three groups of rats were studied after 2 and 12 weeks: (1) controls ; (2) STZ-diabetic rats (STZ rats), and (3) STZ-diabetic rats with insulin implants. Additional rats were treated with losartan (25 mg/kg/day) and/or PD123319 (10 mg/kg/day) for 2 weeks. Kidneys were examined for apoptosis, using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, DNA laddering, and electron microscopy. Immunoblotting determined expression of the proapoptotic protein Bax and of the antiapoptotic protein Bcl-2 in proximal tubules. Results: Diabetes caused a significant increase in apoptosis, involving tubular and interstitial cells of cortex and medulla, but not glomerular cells (2 weeks: controls 264 ± 94 vs. STZ rats 1,501 ± 471 apoptotic nuclei/kidney section; p < 0.02; n = 6–8), an effect reversed by insulin. In STZ rats, ultrastructural examination revealed chromatin condensation and nuclear fragmentation in tubular and interstitial cells. At 2 and 12 weeks, a significant decrease in the expression of the antiapoptotic protein Bcl-2 occurred in STZ rat proximal tubules, with restoration by insulin. In STZ rats, treatment for 2 weeks with losartan or PD123319 inhibited apoptosis in the kidneys, with no additive effect of the combination therapy. Conclusions: Apoptosis occurs in diabetic nephropathy, involving tubular and interstitial cells, an effect reversed by insulin therapy. Furthermore, the effects of AT1 or AT2 receptor blockade suggest that Ang II is involved in mediating apoptosis in the diabetic kidney.
Influence of Cold Storage on Renal Ischemia Reperfusion Injury after Non-Heart-Beating Donor Explantation
Authors: Dittrich Sven , Groneberg David A. , von Loeper Johanna , Lippek Frank , Hegemann Olaf , Grosse-Siestrup Christian , Lange Peter E.
Published: April 2004

Background: Due to the increasing need for kidney donors, transplantation from non-heart-beating donors (NHBD) is currently being practiced more extensively. As detailed studies on the reperfusion injury of these kidneys do not exist so far, a comparison of renal ischemia reperfusion injury scores immediately after organ explantation with injury scores after NHBD organ explantation with subsequent cold storage would be useful. Methods: Non-stored kidneys were compared to a group of kidneys stored for 6.9 ± 1.8 h. Functional analyses were made during 145 min of ex vivo perfusion. Quantitative histological analyses were performed in all kidneys after termination of perfusion. Results: During ex vivo reperfusion, renal vascular resistance was elevated, while creatinine clearance, filtration fraction, renal oxygen consumption, and sodium reabsorption were below normal after non-heart-beating explantation and further decreased after subsequent washing and cold storage. In the kidneys subjected to cold preservation, histologically tubular damage was enhanced, and the total count, as well that for the intraglomerular neutrophil granulocytes were also elevated. Conclusions: Explantation from NHBD causes renal ischemia reperfusion injury. Cold storage augmented deterioration of the kidney as histologically and functionally demonstrated. Thus, preservation times for non-heart-beating kidneys should be carefully reappraised.
Laparoscopic Splenectomy for Hematological Disorders
Authors: Khoursheed M. , Al-Sayegh F. , Al-Bader I. , Kanawati N. , Maroof R. , Asfar S. , Dashti H.
Published: April 2004

Objectives: The aim of this prospective study was to evaluate the safety and feasibility of laparoscopic splenectomy (LS) in patients with hematological disorders of the spleen. Subjects and Methods: Between 1999 and 2001, 15 patients (11 female and 4 male), with a mean age of 30 years, underwent LS after preoperative evaluation. If difficulties were encountered in LS, one trocar site incision was enlarged to 7–8 cm to engage the left hand for hand-assisted laparoscopic splenectomy (HALS) and the procedure was completed. Various parameters were reported, including spleen size as assessed by ultrasound scan, postoperative mortality and morbidity rates, accessory spleen removal, conversion rate, operative times and length of hospital stay. LS was successfully completed in 9 patients (60%) and HALS was performed in 4 patients (26.6%). Two patients required conversion to open splenectomy. Results: The mean operative time was 209 min and the mean hospital stay was 8.1 days. The hospital stay was significantly longer among HALS patients than LS patients. The mean age of patients and splenic size were associated with a significantly higher conversion rate. No deaths were attributed to the procedure. Complications occurred in 2 of 15 patients. Accessory spleens were identified in 2 patients. Conclusions: LS is both a safe and feasible procedure, but it requires great technical care to avoid serious complications.
The Impact of Nurse Understaffing on the Transmission of Hepatitis C Virus in a Hospital-Based Hemodialysis Unit
Authors: Saxena Anil Kumar , Panhotra B.R.
Published: April 2004

Objective: To determine the impact of nurse understaffing on the transmission of hepatitis C virus (HCV) infection in a large hospital-based hemodialysis (HD) unit with a high HCV prevalence. Subjects and Methods: The records of 198 patients (107 males and 91 females) with end-stage renal disease enrolled on long-term HD at King Fahad Hospital and Tertiary Care Center, Hofuf, Saudi Arabia, from August 1995 to August 2000, were retrospectively reviewed. The patients were assigned to HD groups of varying patient-to-nurse (P/N) ratios: group I, 2:1; group II, 3:1, and group III, 4:1. HCV prevalence, seroconversion rates, history of blood transfusion and dialysis age (time span since the initiation of the HD treatment) were recorded and compared. Results: The overall HCV prevalence and seroconversion rate per year were 43.4 and 8.6%, respectively. Group I had the lowest HCV prevalence and annual seroconversion rate (26.8%; 5.3%), followed by group II (43.6%; 8.7%); group III had the highest HCV prevalence and seroconversion rate (71.8%; 14.4%). Anti-HCV positivity was associated with a higher dialysis age. Conclusion: The finding that the patients in the groups with the relatively higher P/N ratio had the significantly higher HCV prevalence and seroconversion rates per year indicates that understaffing is likely to play a major role in the transmission of HCV in HD units, and we suggest that improved staffing may be helpful in reducing the HCV transmission in such dialysis units.
Is Low-Back Pain Prevalent among Kuwaiti Children and Adolescents?
Authors: Shehab Dia , Al-Jarallah Khaled , Al-Ghareeb Fatima , Sanaseeri Shamel , Al-Fadhli Mariam , Habeeb Seham
Published: April 2004

Objective: To measure the magnitude of the problem of low-back pain among 10- to 18-year-old Kuwaiti schoolchildren in Hawalli Governorate. Subjects and Methods: A cross-sectional multistage stratified random sample of 400 schoolchildren (199 males and 201 females) of ages 10–18 years were selected from two junior and two high schools in Hawalli Governorate, Kuwait. Data on age, gender and characteristics of low-back pain such as duration, location and frequency were collected through personal interviews using a questionnaire. Low-back pain was defined as pain in the back from the 12th rib to the buttock area. Results: According to our definition, reported lifetime prevalence of low-back pain was found to be 57.8% (50.8% in male and 64.7% in female students), while the point prevalence was 35% (20.6% in male and 39.3% in female students). More female students reported low-back pain than male students, and the prevalence of low-back pain was found to increase with age in both sexes. The age of onset of low-back pain was 14 years in males and 13 years in females. The majority of students (92.1% in males, 84.6% in females) reported pain in the low back. Almost 46% of students related their low-back pain to accidents. A significantly higher proportion of male students (58.4%, compared to females 36.2%) reported low-back pain caused by accident or with duration of recovery less than a week (21.8% for males as compared to 16.2% for female students). Female students reported more recurrent or continual low-back pain. Conclusion: Low-back pain is common among Kuwaiti students in Hawalli Governorate. Prevalence of low-back pain increased with age in both sexes. Female students reported more frequent low-back pain than male students.
A Pallial Visual Area in the Telencephalon of the Bony Fish Polypterus
Authors: Northcutt R. Glenn , Plassmann Wolfgang , Holmes Preston H. , Saidel William M.
Published: April 2004

The dorsal (P2) and lateral (P3) pallial zones of bichirs receive a substantial projection from nucleus medianus of the posterior tuberculum. Although nucleus medianus does not receive a direct retinal input, its close proximity to ascending tectal efferents suggests that it might receive a tectal input and form a segment of a retinotectal-tubercular pathway to the pallium. In order to test this possibility, evoked responses to light flashes were electrophysiologically recorded and tectal efferents were experimentally determined in bichirs. These experiments suggest that a single visual field exists across the dorsal and lateral pallial zones and that this field is mediated by nucleus medianus, which does receive a direct tectal projection. This visual pathway appears to be uniquely derived and not homologous to any other known pathway in tetrapods. Furthermore, these results support the contention that the P2 and P3 pallial zones in bichirs are subdivisions of a single pallial zone.
Fiber Type Composition of the Muscle Responsible for Throat Fan Extension in Green Anole Lizards
Authors: Rosen G.J. , O’Bryant E.L. , Swender D. , Wade J.
Published: April 2004

Throat fan (dewlap) extension is sexually dimorphic in green anole lizards (Anolis carolinensis). Males have larger dewlaps which they display more frequently than females. Correlated with the behavior, sexual dimorphisms occur in the skeletal, muscular and neural structures responsible for dewlap extension in green anoles. We used histochemical techniques to stain for myosin ATPase and succinate dehydrogenase (SDH) to determine whether sex differences also exist in fiber type composition of the ceratohyoideus, the muscle that extends the dewlap. Based on the staining pattern for the two enzymes, four fiber types were identified: fast-oxidative-glycolytic (FOG), fast-glycolytic (FG), slow-oxidative (SO), and tonic. In the ceratohyoideus of both sexes, the predominate fiber types were FOG (∼43%) and FG (∼34%). Also in both males and females, the FOG and FG fibers had approximately twice the cross-sectional area of the SO and tonic fibers. No sex differences occurred in the percentages of FOG and FG fibers. However, males had a greater percentage of tonic fibers than females, whereas females had a greater percentage of SO fibers than males. The high proportion of FOG fibers in the anole ceratohyoideus makes it similar to other relatively fatigue-resistant muscles used in movements of moderate speed and duration. Although the precise role of tonic fibers in dewlap extension is not known, the greater percentage of these fibers in the male ceratohyoideus might be required to stabilize or maintain extension of the large dewlap apparatus in males.