bluuebunny/crossref_metadata_2025 huggingface dataset:
Neglectful Behavior by Parents in the Life History of University Students in 17 Countries and Its Relation to Violence Against Dating Partners
Authors: Straus Murray A. , Savage Sarah A.
Published: March 2005

This article reports the prevalence of neglectful behavior by parents of university students in 17 nations (6 in Europe, 2 in North America, 2 in Latin America, 5 in Asia, Australia, and New Zealand) and tests the hypothesis that neglect is a risk factor for violence against a dating partner. The percentage at each university who experienced neglectful behavior ranged from 3.2% to 36% (median 12%), and the percentage who perpetrated violence against dating partners ranged from 15% to 45% (median 28%). Multilevel modeling found that the more neglectful behavior experienced as a child the greater the probability of assaulting and injuring a dating partner and that the link between experiencing neglect and perpetrating violence is stronger at universities in which dating violence is more prevalent. Efforts to help parents avoid neglectful behavior can make an important contribution to primary prevention of partner violence and probably also other forms of child maltreatment.
Exploring Connections Between Human Resource Development and Creativity
Authors: Waight Consuelo L.
Published: March 2005

This article sets the stage for exploring the connections between creativity and human resource development (HRD). It signals the significance of exploring creativity and HRD by looking at knowledge workplaces, workforce projections, work values, occupation projections, on-the-job training, and entrepreneurship. The article also shows how research on creativity and HRD has examined similar learning and performance variables.
Creativity in the Context of Team Diversity: Team Leader Perspectives
Authors: Egan Toby Marshall
Published: March 2005

In spite of demands for teaming and creative outputs in organizations and for increasing workforce diversity overall, to date researchers have only scratched the surface regarding team creativity and appear to have ignored the role of diversity altogether. Fortune 500 team leaders identified as both successful in leading creative teams and who identify team diversity as important to their successes were interviewed for this study. In addition to several other key elements, team leaders credited a mix of employees with different characteristics as a key reason for team development of creative outputs directly impacting organizational success. Study findings are discussed and compared to related research. Recommendations for further study are provided.
Internal tandem duplications of the FLT3 gene are present in leukemia stem cells
Authors: Levis Mark , Murphy Kathleen M. , Pham Rosalyn , Kim Kyu-Tae , Stine Adam , Li Li , McNiece Ian , Smith B. Douglas , Small Donald
Published: March 2005

Internal tandem duplication mutations of the FLT3 gene (FLT3/ITD mutations) are the most frequent molecular abnormality in acute myeloid leukemia (AML) and are associated with a poor overall survival. While the normal FLT3 receptor is expressed in early hematopoietic progenitor cells, it has not been determined whether FLT3 mutations are present in the leukemic stem cells. In this study, we sorted primary AML samples into stem cell-enriched CD34+/CD38- fractions and then analyzed the sorted and unsorted cells for the FLT3 mutant-wild-type ratio. In each case, the FLT3 mutant-wild-type ratio was not changed by selection of CD34+/CD38- cells, implying that the mutations are present in the leukemic stem cells. We used the stem cell-enriched fraction to engraft nonobese diabetic-severe combined immunodeficient (NOD-SCID) mice and then confirmed that the FLT3/ITD mutation was present in the resultant engrafted marrow. As a final test of the importance of FLT3/ITD signaling in this engraftment model, we used a small molecule FLT3 inhibitor, CEP-701, to inhibit engraftment of FLT3/ITD stem cells. Taken together, these experiments establish that the FLT3/ITD mutations are present in leukemia stem cells, and that FLT3 inhibitors may have activity against these cells. (Blood. 2005;106:673-680)
Hepcidin levels in humans are correlated with hepatic iron stores, hemoglobin levels, and hepatic function
Authors: Détivaud Lénaïck , Nemeth Elizabeta , Boudjema Karim , Turlin Bruno , Troadec Marie-Bérengère , Leroyer Patricia , Ropert Martine , Jacquelinet Sylvie , Courselaud Brice , Ganz Tomas , Brissot Pierre , Loréal Olivier
Published: March 2005

Hepcidin, a key regulator of iron metabolism, is synthesized by the liver. Hepcidin binds to the iron exporter ferroportin to regulate the release of iron into plasma from macrophages, hepatocytes, and enterocytes. We analyzed liver samples from patients undergoing hepatic surgery for cancer or receiving liver transplants and analyzed correlations between clinical parameters and liver hepcidin mRNA and urinary hepcidin concentrations. Despite the many potential confounding influences, urinary hepcidin concentrations significantly correlated with hepatic hepcidin mRNA concentrations, indicating that hepcidin quantification in urine is a valid approach to evaluate hepcidin expression. Moreover, we found in humans that hepcidin levels correlated with hepatic iron stores and hemoglobin levels and may also be affected by hepatic dysfunction. (Blood. 2005;106:746-748)
A long-term follow-up study on hepatitis B surface antigen–positive patients undergoing allogeneic hematopoietic stem cell transplantation
Authors: Hui Chee-kin , Lie Albert , Au Wing-yan , Leung Yu-hung , Ma Shing-yan , Cheung Winnie W. W. , Zhang Hai-ying , Chim Chor-sum , Kwong Yok-lam , Liang Raymond , Lau George K. K.
Published: March 2005

The long-term hepatic complications after allogeneic hematopoietic stem cell transplantation (HSCT) in hepatitis B virus (HBV) endemic area are unknown. We examined the serological and liver-related outcome of 803 consecutive patients who received allogeneic HSCTs, with a median follow-up period of 83 months (range, 0.5-155 months). Late HBV-related hepatitis occurred in 2 of the 721 hepatitis B surface antigen–negative (HBsAg–) recipients compared with 16 of the 82 HBsAg+ recipients after HSCT (0.3% vs 19.5%; P < .001 by log-rank). Liver cirrhosis developed in 8 of the 82 HBsAg+ recipients compared with none of the 721 HBsAg– recipients (9.8% vs 0%; P < .001 by log-rank). Twenty of the 31 (64.5%) HBsAg+ recipients of hematopoietic stem cells from donors with natural immunity to HBV had sustained serologic clearance of HBsAg after HSCT. Eight of the 62 recipients without sustained HBsAg clearance compared with none of the 20 recipients with sustained HBsAg clearance developed liver cirrhosis (12.9% vs 0%; P = .02 by log-rank). Our study showed that long-term hepatic complications occur in a significant proportion of HBsAg+ patients after HSCT and the incidence of liver cirrhosis is reduced in those with sustained serologic clearance of HBsAg after HSCT.
A2 gene of Old World cutaneous Leishmania is a single highly conserved functional gene
Authors: Garin Yves JF , Meneceur Pascale , Pratlong Francine , Dedet Jean-Pierre , Derouin Francis , Lorenzo Frédéric
Published: March 2005

Background

Leishmaniases are among the most proteiform parasitic infections in humans ranging from unapparent to cutaneous, mucocutaneous or visceral diseases. The various clinical issues depend on complex and still poorly understood mechanisms where both host and parasite factors are interacting. Among the candidate factors of parasite virulence are the A2 genes, a family of multiple genes that are developmentally expressed in species of the Leishmania donovani group responsible for visceral diseases (VL). By contrast, in L. major determining cutaneous infections (CL) we showed that A2 genes are present in a truncated form only. Furthermore, the A2 genomic sequences of L. major were considered subsequently to represent non-expressed pseudogenes [1]. Consequently, it was suggested that the structural and functional properties of A2 genes could play a role in the differential tropism of CL and VL leishmanias. On this basis, it was of importance to determine whether the observed structural/functional particularities of the L. major A2 genes were shared by other CL Leishmania, therefore representing a proper characteristic of CL A2 genes as opposed to those of VL isolates.

Methods

In the present study we amplified by PCR and sequenced the A2 genes from genomic DNA and from clonal libraries of the four Old World CL species comparatively to a clonal population of L. infantum VL parasites. Using RT-PCR we also amplified and sequenced A2 mRNA transcripts from L. major.

Results

A unique A2 sequence was identified in Old World cutaneous Leishmania by sequencing. The shared sequence was highly conserved among the various CL strains and species analysed, showing a single polymorphism C/G at position 58. The CL A2 gene was found to be functionally transcribed at both parasite stages.

Conclusion

The present study shows that cutaneous strains of leishmania share a conserved functional A2 gene. As opposed to the multiple A2 genes described in VL isolates, the CL A2 gene is unique, lacking most of the nucleotide repeats that constitute the variable region at the 5'end of the VL A2 sequences. As the variable region of the VL A2 gene has been shown to correspond to a portion of the protein which is highly immunogenic, the present results support the hypothesis of a possible role of the A2 gene in the differential tropism of CL and VL leishmania parasites.
Chronic intestinal pseudo-obstruction associated with biliary tract dilatation in a patient with systemic lupus erythematosus
Authors: Pardos-Gea J , Ordi-Ros J , Selva A , Perez-Lopez J , Balada E , Vilardell M
Published: March 2005

We present the case of a 57-year old female patient diagnosed with systemic lupus erythematosus (SLE) along with glomerulonephritis and chronic intestinal pseudo-obstruction (CIPO). Dilatation of bile and pancreatic ducts not associated with malignant or litiasic obstruction is reported. The combination of bile duct associated with CIPO in a patient with lupus has not been previously reported in the literature and it probably suggests a smooth muscle dysmotility.
Spontaneous Achilles tendon rupture in a patient with systemic lupus erythematosus due to ischemic necrosis after methyl prednisolone pulse therapy
Authors: Chiou Y-M , Lan J-L , Hsieh T-Y , Chen Y-H , Chen D-Y
Published: March 2005

Spontaneous tendon rupture in a patient with systemic lupus erythematosus (SLE) is a rare but potentially disabling complication. Minor trauma, local inflammation and long term corticosteroid therapy are regarded as possible causes. However, ischemic necrosis of the tendon resulting from hypercoagulability and methyl prednisolone (MTP) pulse therapy has not been reported. We present a 20-year old female, newly diagnosed with lupus, who has high titer antiphospholipid antibodies, hyperhomocysteinemia and protein S deficiency. Her severe clinical symptoms of lupus were improved after MTP pulse therapy. Several days later, cold sensation over the right lower leg developed. On day 15 after pulse therapy, acute onset of right heel pain occurred when she was ascending stairs. Rupture of the right Achilles tendon was demonstrated by sonography and MRI. A Doppler sonography revealed narrowing and abrupt cessation of blood flow in the right popliteal artery. Heparin treatment was started. The angiography performed two days after heparinization revealed narrow caliber and decreased flow of the right tibial artery below the right ankle. Surgical repair of the tendon was successful and the pathology of the resected tendon revealed focal necrosis, degeneration and capillary proliferation. MTP pulse therapy in a lupus patient with hypercoaguable state with hyperhomocysteinemia, protein S deficiency and high titer antiphospholipid antibodies may cause spontaneous tendon rupture.
Association of leukocyte CR1 gene transcription with the disease severity and renal involvement in systemic lupus erythematosus
Authors: Verma Jyotsna , Arora Vaishali , Marwaha Vishal , Kumar Ashok , Das Nibhriti
Published: March 2005

The reduced level of complement receptor 1 (CR1) on erythrocytes is speculated as a key mechanism contributing to immune complex (IC) overload and exaggerated complement (C) activation in systemic lupus erythematosus (SLE). Comparatively, fewer studies documented lower levels of CR1 on leukocytes and glomerular podocytes in this disease. The decline in E-CR1 is largely believed as an acquired phenomenon caused due to the proteolytic cleavage of CR1 from erythrocyte membrane. The mechanism underlying reduced CR1 expression on nucleated cells is under constant investigation. Recently, reduced leukocytes CR1 gene transcription had been demonstrated in SLE and was suggested as the main cause of decline in leukocyte CR1 (L-CR1). The relationship of L-CR1 gene transcription with severity and pathophysiology of disease needs to be elucidated. We determined the levels of L-CR1 in 30 active SLE patients and compared with normal healthy controls (n = 30). Patients were categorized into two groups i.e., with nephritis (n = 14) or without nephritis (n = 16). The expression of L-CR1 at transcriptional level was correlated with the levels of serum CIC, C3 and anti dsDNA antibodies. The levels of L-CR1 transcription were significantly reduced in all SLE patients as compared to controls (P, 0.001). This decline in L-CR1 however, was more marked in patients with nephritis than those without nephritis. In addition, the serum levels of CIC, anti dsDNA antibodies were higher and the levels of serum C3 were lower than the normal range in the patients. The difference was much more marked in SLE patients with nephritis than those without nephritis. The levels of L-CR1 transcription correlated negatively with the levels of CIC and anti dsDNA antibodies and positively with serum C3 levels. Thus, between SLE patients with and without nephritis, we found significant difference in the levels of L-CR1 transcription (P, 0.01), CIC (P, 0.05), anti dsDNA antibodies (P, 0.01) and C3 (P, 0.01). Our findings suggest that L-CR1 is drastically reduced in patients with severe form of SLE, i.e., lupus nephritis. Determination of L-CR1 expression at transcriptional level in addition to disease hallmarks like C3, CIC and anti-dsDNA antibodies may facilitate the assessment of severity of SLE and discrimination between patients with or without renal involvement.
Relationship of quality of life and physical function measures with disease activity in children with systemic lupus erythematosus
Authors: Moorthy L N , Harrison M J , Peterson M , Onel K B , Lehman T JA
Published: March 2005

The objective of this study is to assess relationship of systemic lupus erythematosus (SLE) activity with quality of life (QOL) and physical function and determine which is more closely correlated with SLE activity in children; and identify factors critical to children’s QOL. In this cross-sectional study, children with SLE and parents completed corresponding versions of physical function (Childhood Health Assessment Questionnaire -CHAQ), and QOL (Pediatric Quality of Life Inventory -PedsQL Generic/Rheumatology modules) questionnaires. SLE Disease Activity Index (SLEDAI), Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI), severity, self-concept and socioeconomic status (SES) were measured. For 24 children, CHAQ scores significantly correlated with SLEDAI (rho = 0.4, p = 0.04), SDI (rho = 0.6, p = 0.004), and associated with severity (p = 0.03). PedsQL scores did not significantly correlate with above parameters. Higher self-concept/SES correlated (p, 0.05) with better physical function and QOL. For 19 parents, the only significant correlation was between SLEDAI and Worry domain - Rheumatology module (rho = 0.5, p = 0.01). Lack of strong correlation of disease activity with QOL and physical function suggests that they are different constructs with partial overlap, and should be considered collectively while evaluating the impact of SLE on children/families. Self-concept and SES should be assessed while measuring QOL in children. Larger sample is required to confirm results.
Antiproteinuric effect of ARB in lupus nephritis patients with persistent proteinuria despite immunosuppressive therapy
Authors: Kanda H , Kubo K , Tateishi S , Sato K , Yonezumi A , Yamamoto K , Mimura T
Published: March 2005

Recent immunosuppressive treatments for lupus nephritis have improved renal survival rate, however, there still exists lupus nephritis refractory to these treatments. Angiotensin receptor blockers (ARBs) are known not only to decrease blood pressure but also to have an independent renoprotecting effect by interrupting renin-angiotensin system. The aim of this study was to evaluate whether ARBs have an additive effect on refractory lupus nephritis. Enrolled in this trial were twelve patients with lupus nephritis who were diagnosed by renal biopsy and remained proteinuria despite corticosteroids and/or immunosuppressive treatments. ARB, losartan or candesartan, was administered for six months. Various clinical parameters were compared before and after ARB administration. Proteinuria decreased after ARB treatment in 83% of the patients and the median amount of proteinuria significantly decreased from 2530 mg/gCr to 459 mg/gCr (P = 0.03). In addition, serum albumin and cholesterol levels were significantly improved. Systolic blood pressure significantly decreased, but none had symptoms of hypotension. The antiproteinuric effect of ARB did not correlate with the reduction of blood pressure. Interestingly, higher total complement activity levels before ARB treatment were associated with a greater reduction of proteinuria. The addition of ARB would be a safe and effective treatment for lupus nephritis with persistent proteinuria despite corticosteroids and/or immunosuppressive treatments.
MHC class I expression regulates susceptibility to spontaneous autoimmune disease in (NZBxNZW)F1 mice
Authors: Mozes E , Lovchik J , Zinger H , Singer D S
Published: March 2005

(NZBxNZW)F1 mice spontaneously develop with age an autoimmune disease that resembles the human disease, systemic lupus erythematosus (SLE). Previous studies have demonstrated that susceptibility to experimentally induced SLE depended on the expression of MHC class I molecules: mice deficient in β2-microglobulin did not express cell surface class I and were resistant to the induction of experimental SLE. Furthermore, the spontaneous SLE-like disease of (NZBxNZW)F1 mice was ameliorated by treatment with an agent that reduces MHC class I expression, methimazole (MMI). In the present study, the role of MHC class I has been examined in (NZBxNZW)F1 mice deficient in β2-microglobulin expression. Homozygous (NZBxNZW)F1b2m-/- mice do not express class I or develop CD8+ T cells. Surprisingly, they show an increased susceptibility to disease. In sharp contrast, heterozygous (NZBxNZW)F1β2m+/- express class I, albeit at reduced levels, develop normal levels of CD8+ T cells and are less susceptible to autoimmune disease, relative to their wild-type litter mates. Taken together, these findings suggest that class I expression regulates the development of disease, both positively and negatively. We speculate that MHC class I expression itself confers susceptibility to disease through presentation of self-peptides, while also selecting for a CD8+ suppressor T cell population that mitigates disease.
Effect of flavones on rat brain and lung matrix metalloproteinase activity measured by film in-situ zymography
Authors: Sasaki K , Tateoka N , Ando H , Yoshizaki F
Published: March 2005

We have evaluated the inhibitory activity of flavone, nobiletin, and heptamethoxyflavone on matrix metalloproteinase (MMP) activity in the rat. MMP in 9000-g supernatant fraction of lung homogenate was activated by p-aminophenyl mercuric acetate (APMA), and gelatinolytic activity was determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) followed by Coomassie staining. This activity should be related to MMP-2 and/or MMP-9 and was confirmed by gelatin zymography. Fluorescent-conjugated collagen used as a substrate for collagenolytic activity was investigated by SDS-PAGE also. The film in-situ zymography method was applied to rat brain and lung tissue in the same manner. Flavone and nobiletin inhibited the APMA-stimulated gelatinolytic activity and also the collagenolytic activity by more than 75%. The film in-situ zymography method indicated that these compounds might be potent inhibitors of MMP, suggesting the specific inhibition of localized MMP in brain hippocampus and/or lung terminal bronchioles, which may contribute to the prevention of some types of brain disease or cancer invasion and metastasis.
Effect of aqueous Enicostemma littorale Blume extract on key carbohydrate metabolic enzymes, lipid peroxides and antioxidants in alloxan-induced diabetic rats
Authors: Srinivasan M , Padmanabhan M , Prince P Stanely Mainzen
Published: March 2005

The present study investigates the effect of oral administration of an aqueous Enicostemma littorale whole plant extract on some key carbohydrate metabolic enzymes and antioxidant defence in alloxan-induced diabetes in rats. Rats were rendered diabetic by alloxan (150 mg kg−1 body weight) administration. Oral administration of E. littorale extract for 45 days increased the activity of hexokinase and decreased the activities of glucose 6-phosphatase and fructose 1,6-bisphosphatase significantly in the serum, liver and kidney of diabetic rats. The extract lowered the concentration of thiobarbituric acid reactive substances and lipid hydroperoxides significantly in brain and increased it significantly in heart in diabetic rats. E. littorale administration increased the concentration of reduced glutathione and the activity of glutathione peroxidase in diabetic rats. The activities of superoxide dismutase and catalase were increased significantly by E. littorale treatment in diabetic rats. The effect of a 2 g kg−1 dose was greater than that of a 1 g kg−1 dose. Insulin (6 units kg−1) normalized all the parameters in diabetic rats. Our study has provided evidence for the antidiabetic activity of E. littorale aqueous extract. This study can also be extrapolated to clinical studies in future.
Nifedipine enhances cGMP production through the activation of soluble guanylyl cyclase in rat ventricular papillary muscle
Authors: Seya Kazuhiko , Furukawa Ken-Ichi , Yoshida Kazuhiko , Narita Reina , Motomura Shigeru
Published: March 2005

It is known that nifedipine, an L-type calcium channel blocker, increases cGMP production, which partially contributes to the relaxation of vascular smooth muscle. The aim of our investigation was to clarify whether or not nifedipine regulates cGMP production, which has a physiological role in cardiac muscle. To measure contractile responses and tissue cGMP levels, left ventricular papillary muscles prepared from male Wistar rats (350–400 g) were mounted in the isolated organ chamber under isometric conditions and electrically paced by means of platinum punctate electrodes (1 Hz, 1 ms duration). In papillary muscle preparation, the negative inotropic effect induced by nifedipine (30 to 300 nm) was significantly inhibited in the presence of ODQ (1H-[1,2,4]oxidazolo[4,3-a]quinoxaline-1-one; 10 μm), a soluble guanylyl cyclase inhibitor. Furthermore, nifedipine (100 nm) strongly increased the tissue cGMP level, which was significantly decreased in the presence of ODQ. On the other hand, NG-monomethyl-l-arginine (100 μm), a nitric oxide synthase inhibitor, did not inhibit either the negative inotropic effect or cGMP production induced by nifedipine. These results indicate that in rat left ventricular papillary muscle, nifedipine augments its negative inotropic effect at least partly through direct activation of cardiac soluble guanylyl cyclase but not nitric oxide synthase.
Selective β1-adrenoreceptor blocking activity of newly synthesized acyl amino-substituted aryloxypropanolamine derivatives, DPJ 955 and DPJ 890, in rats
Authors: Nandakumar K , Bansal S K , Singh Randhir , Bodhankar S L , Jindal D P , Coumar Mohane S , Balaraman R , Bhardwaj S H
Published: March 2005

The in-vivo β-adrenoreceptor antagonistic activity of test compounds DPJ 955 and DPJ 890 was assessed against β-adrenoreceptor agonist (isoprenaline) induced tachycardia in anaesthetized rats. The selectivity to block isoprenaline responses on different β-adrenoreceptor subtypes (β1, β2 and β3) of the test compounds was carried out on isolated rat right atria, isolated rat uterus and isolated rat colon preparations, respectively. Intravenous injection of isoprenaline alone in anaesthetized rats caused hypotension and tachycardia. DPJ 955 or DPJ 890 alone produced a fall in mean arterial pressure and bradycardia in a dose-dependent manner. Administration of isoprenaline to anaesthetized rats pre-treated with test compounds significantly blocked both the tachycardial and hypotensive responses induced by isoprenaline. The test compounds shifted the concentration response curves of isoprenaline towards the right for isolated rat right atrial preparations, rat uterus and rat colon, indicating β1, β2 and β3 adrenoreceptor blockade, respectively. The selectivity ratio for β1/β-adrenoreceptors to DPJ 955 and DPJ 890 was 64.6 and 83.2, respectively. DPJ 890 was more potent in blocking β1-adrenoreceptors and was more selective towards β1 receptors than to other β-adrenoreceptor subtypes. In conclusion, DPJ 955 and DPJ890 have β-adrenoreceptor blocking activity with high selectivity for the β1-adrenoreceptor subtype.
Mechanism of cell death induced by cationic dendrimers in RAW 264.7 murine macrophage-like cells
Authors: Kuo Jung-hua Steven , Jan Ming-shiou , Chiu Hsuan Wen
Published: March 2005

Cationic dendrimers possess attractive nano-sized architectures that make them suitable as targeted drug/gene delivery systems. However, very little is known about their mechanisms of cell death in cellular systems. In the current study, the apoptotic and necrotic effects of starburst polyamidoamine (PAMAM) and polypropylenimine (DAB) dendrimers in cultured RAW 264.7 murine macrophage-like cells were investigated. Cationic dendrimer treatment produced a typically dose-dependent cytotoxic effect on macrophage cells. RAW 264.7 cells exposed to cationic dendrimers exhibited morphological features of apoptosis. Apoptotic ladders were observed in DNA extracted from RAW 264.7 cells treated with cationic dendrimers. Analysis from flow cytometry demonstrated an increase in hypodiploid DNA population (sub-G1) and a simultaneous decrease in diploid DNA content, indicating that DNA cleavage occurred after exposure of the cells to cationic dendrimers. Also, cells treated with DAB dendrimer induced a higher percentage of sub-G1 population than those treated with PAMAM dendrimer at the same dose. In addition, it was shown that pre-treatment of RAW 264.7 cells with the general caspase inhibitor zVAD-fmk prevented some degree of apoptosis induced by cationic dendrimers, suggesting that apoptosis in macrophage cells involves a caspasedependent pathway. Macrophage cells were also found to be sensitive to induction of apoptosis by dendrimers, whereas NIH/3T3 cells (mouse fibroblast) and BNL CL.2 (mouse liver) cells did not undergo apoptosis. These results could be helpful for optimizing the biocompatibility of dendrimers used for targeted drug/gene delivery.
Citrus extract modulates genotoxicity induced by cyclophosphamide in mice bone marrow cells
Authors: Hosseinimehr Seyed Jalal , Karami Mohmmad
Published: March 2005

The protective effect of citrus extract was investigated by using the micronucleus assay for anticlastogenic activity in mouse bone marrow cells; liver glutathione (GSH) content was determined against toxicity induced by cyclophosphamide. Mice were orally (gavage) pretreated with solutions of citrus peel extract (Citrus aurantium var. amara) prepared at three different doses (100, 200 and 400 mg kg−1 body weight) for 7 consecutive days. Then mice were injected intraperitoneally on the seventh day with cyclophosphamide (50 mg kg−1) and after 24 h killed for the evaluation of micronucleated polychromatic erythrocytes (MnPCEs) in bone marrow cells. Non-protein thiol levels in liver were estimated in mice injected with citrus extract with or without cyclophosphamide treatment. Administration of citrus extract before cyclophosphamide treatment significantly reduced the frequency of MnPCEs in mice bone marrow compared with the group treated with cyclophosphamide alone (P<0.0001–0.05). Citrus extract at a dose of 400 mg kg−1 reduced MnPCEs 2.8 fold against genotoxicity induced by cyclophosphamide. Administration of cyclophosphamide depleted the GSH level in liver. Citrus extract showed excellent scavenging effects on 1,1-diphenyl-2-picryl hydrazyl radical (DPPH) at a concentration of 1.6 mg mL−1. Application of citrus extract 1 h before cyclophosphamide treatment allowed GSH content to reach the normal level. It appeared that citrus extract, particularly flavonoids constituents with antioxidative activity, may return the GSH level to normal in stress conditions and reduces genotoxicity induced by cyclophosphamide in bone marrow cells.
Experimental modelling of drug membrane permeability by capillary electrophoresis using liposomes, micelles and microemulsions
Authors: Örnskov Eivor , Gottfries Johan , Erickson Magnus , Folestad Staffan
Published: March 2005

Capillary electrophoresis (CE) was evaluated as an in-vitro format for experimental modelling of membrane permeability using only nanogram quantities of drug compounds. The rationale for the CE technique emanates from emulation of a lipid-like pseudo-stationary phase that governs separations mainly as a result of differences in molecular size, lipophilicity, hydrogen bonding and charge, all of which also have a strong influence on in-vivo drug absorption. By means of micellar, microemulsion and liposome electrolytes, the migration behaviour was studied at 37°C for 22 model drug compounds. The generated CE retention factor data were then compared with membrane permeability reference data. Both simple log D and more common Caco-2 cell parameters were evaluated. In addition, permeation through intestinal segments of rat ileum and rat colon was included. An improved correlation was obtained in the order: micellar<microemulsion<liposome systems. Although the correlation for the best liposome CE system was only R2 = 0.77, the evaluation results for all emphasized the strength and flexibility of CE for assessing specific drug-membrane interaction through tailor-made lipophilic media.
Tumour targeting: biological factors and formulation advances in injectable lipid nanoparticles
Authors: Shenoy V S , Vijay I K , Murthy R S R
Published: March 2005

Cancer chemotherapeutic agents are often administered systemically. Following systemic administration, numerous biological factors associated with the tumours influence the delivery of the drugs to the tumours. These factors have been extensively studied for the last 2 decades. The influence of these biological factors has brought about a drastic change in the design of drug delivery systems to solid tumours. This review discusses the various biological factors influencing drug delivery to tumours and the subsequent development of injectable delivery systems (i.e., lipid-based nanoparticles (SLNs)) for adequate delivery of drug to solid tumours.
Decompressive Hemicraniectomy for Acute Disseminated Encephalomyelitis: Case Report
Authors: Refai Daniel , Lee Max C. , Goldenberg Fernando D. , Frank Jeffrey I.
Published: March 2005

OBJECTIVE AND IMPORTANCE:

Acute disseminated encephalomyelitis (ADEM) varies widely in symptoms and severity. Some cases are associated with massive life-threatening cerebral edema refractory to conventional medical management.

CLINICAL PRESENTATION:

A 51-year-old woman with ADEM who developed severe brain swelling and herniation despite aggressive medical management is described.

INTERVENTION:

A decompressive hemicraniectomy and durotomy led to rapid improvement and an excellent outcome.

CONCLUSION:

This case report reinforces the place of this procedure in the armamentarium of treatment options for patients with medically refractory brain swelling and elevated intracranial pressure caused by ADEM. The potential for an increase in the incidence of ADEM with more frequent smallpox vaccinations emphasizes the significance of redefining the full range of management options for this treatable disease.
Surgical Outcome in Rheumatoid Ranawat Class IIIb Myelopathy
Authors: Nannapaneni Ravindra , Behari Sanjay , Todd Nicholas V.
Published: March 2005

OBJECTIVE:

Rheumatoid arthritis frequently affects the craniovertebral junction (CVJ) and may lead to severe neck pain, quadriparesis, and respiratory dysfunction. Surgery in rheumatoid nonambulatory (Ranawat Class IIIb) patients carries a significant risk. This study presents the surgical outcome of Class IIIb patients with CVJ rheumatoid myelopathy and reviews the literature.

METHODS:

One hundred twelve consecutive patients with rheumatoid cervical myelopathy underwent surgical decompression and stabilization. Thirty-two of the patients (mean age, 66.81 ± 10.25 yr) with CVJ rheumatoid arthritis were in Class IIIb, and all had atlantoaxial subluxation. A halo brace was applied before surgery and continued during surgery. Eleven patients with reducible atlantoaxial subluxation underwent direct posterior fusion. Twenty-one patients with fixed atlantoaxial subluxation underwent transoral decompression and then posterior fusion while they were under anesthesia.

RESULTS:

At a mean follow-up of 39 months, four patients improved to Class II and 14 improved to Class IIIa, whereas six remained in Class IIIb. Neck pain was relieved in all patients. There was one perioperative death after transoral surgery (posterior fusion not done), and seven other patients died subsequently of causes unrelated to surgery. The morbidity of surgery included construct failure, cerebrospinal fluid leak, superficial wound or graft donor site infection, transient dysphagia, and lung infection.

CONCLUSION:

A large subset of patients with CVJ rheumatoid myelopathy may reach Class IIIb. These patients have unique management considerations. Surgery (despite high morbidity) often remains the best therapeutic option available to them. Improvement of even one grade in their Ranawat score from Class IIIb to Class IIIa brought about by surgery confers on them a significant benefit in terms of their quality of life and survival.
Assessment of the Learning Curve for Lumbar Microendoscopic Discectomy
Authors: Nowitzke Adrian M.
Published: March 2005

OBJECTIVE:

An understanding of the learning curve of a new surgical procedure is essential for its safe clinical integration, teaching, and assessment. This knowledge is currently deficient for lumbar microendoscopic discectomy (MED). The present article aims to profile the learning curve for MED of an individual surgeon in a hospital not previously exposed to this procedure.

METHODS:

The first 35 cases of MED for posterolateral lumbar disc prolapse causing radiculopathy performed at the Princess Alexandra Hospital, Brisbane, Australia, were studied prospectively. The learning curve was assessed using surgery time, conversion rate, complication rate, surgeon “comfort,” and key learning steps.

RESULTS:

The duration of surgical operating time decreased over the course of the study, initially rapidly and then more gradually. There were three conversions to open discectomy in the first 7 cases and none in the next 28 cases. The complexity of cases increased over the series, and the complication rate decreased. The asymptote of the learning curve seems to be approximately 30 cases. The specific learning tasks of MED include lateral lamina radiology, scope vision, visuospatial orientation, smaller field of view, angle of approach and tube position, and care and handling of endoscope equipment.

CONCLUSION:

A learning curve for MED has been demonstrated. Further assessment of this curve for a population of surgeons is necessary before a clinical assessment of open discectomy versus MED can be embarked upon.
Surgical Site Infections after Pediatric Intracranial Surgery for Craniofacial Malformations: Frequency and Risk Factors
Authors: Yeung Laurence C. , Cunningham Michael L. , Allpress Amanda L. , Gruss Joseph S. , Ellenbogen Richard G. , Zerr Danielle M.
Published: March 2005

OBJECTIVE:

Surgical site infections (SSIs) after pediatric intracranial surgery for craniofacial malformations are relatively common and potentially serious nosocomial infections. Despite this, few studies have been published on this topic. We performed a retrospective study to determine the incidence of and factors associated with SSIs after intracranial surgery for craniofacial malformations at a single multidisciplinary craniofacial center during a 6-year period.

METHODS:

Retrospective chart review was performed on 254 patients who underwent 281 intracranial procedures during a 6-year period. Patients with SSIs (cases) were compared with those without SSIs (controls). National Nosocomial Infection Surveillance System criteria were used to identify cases of SSI.

RESULTS:

SSIs occurred in 9 (3.2%) of 281 intracranial procedures that took place during the study period. Factors associated with an SSI included a complicated diagnosis comprising a diagnosis of syndromic craniosynostosis, frontonasal dysplasia, or oblique facial cleft (odds ratio [OR], 13.0; 95% confidence interval [CI], 2.6–64.4); duration of surgery longer than 426 minutes (OR, 12.1; 95% CI, 2.4–59.9); closure of skin under tension (OR, 12.5; 95% CI, 3.0–52.6); use of bovine pericardium (OR and 95% CI undefined); more than four surgeons present during surgery (OR, 6.3; 95% CI, 1.2–32); pediatric intensive care unit stay longer than 2 days (OR, 10.8; 95% CI, 2.2–53.3); and use of a ventilator after surgery (OR, 4.8; 95% CI, 1.2–18.6).

CONCLUSION:

In this study, the presence of a complicated diagnosis and a number of other factors were associated with an SSI after pediatric intracranial surgery for craniofacial malformations. We speculate that a complicated diagnosis may be a marker for other factors that contribute to the risk of an SSI. Future studies investigating SSIs after intracranial surgery should consider these factors.
Bilateral Reversible Deafness after Surgery for Unilateral Epidermoid Tumor: An Unusual Complication: Case Report
Authors: Colpan Mustafa Efkan , Sekerci Zeki , Berk Caglar
Published: March 2005

OBJECTIVE AND IMPORTANCE:

We present an unusual complication of bilateral hearing loss after surgery for unilateral epidermoid tumor situated at the right pontocerebellar junction. The neurosurgeon must know the possible causes of this catastrophic complication and should take every possible measure to avoid it.

CLINICAL PRESENTATION:

A 43-year-old male patient presented with progressive hearing loss in the right ear. A radiological examination demonstrated a mass lesion at the right pontocerebellar junction. A pure tone audiogram revealed sensorineural hearing impairment of the right ear. A brainstem auditory evoked potential test confirmed this with reduced amplitudes and a prolonged I–V interval.

INTERVENTION:

The patient was operated on via a right paramedian suboccipital craniectomy. The tumor was completely excised, and all of the cranial nerves were preserved during the operation. Postoperatively, the patient developed total bilateral hearing loss, which improved significantly over time.

CONCLUSION:

Controlled cerebrospinal fluid drainage during exposure and tumor excision may reduce the possibility of shift and traction on the neural structures and help to prevent ischemic injury. Frequent irrigation of the surgical field and minimizing the spilling of the tumor contents may reduce the risk of chemical irritation. The use of corticosteroids may also help during the postoperative period.
Factors Associated with Outcome after Hemicraniectomy for Large Middle Cerebral Artery Territory Infarction
Authors: Curry William T. , Sethi Manish K. , Ogilvy Christopher S. , Carter Bob S.
Published: March 2005

OBJECTIVE:

Large or malignant middle cerebral artery infarction is associated with a high mortality rate. Hemicraniectomy reduces intracranial pressure and has been demonstrated to increase survival. Questions remain regarding selection of patients for surgery and functional outcomes.

METHODS:

We retrospectively reviewed the charts, operative reports, and images of patients who underwent hemicraniectomy for cerebral infarction at our institution between 1990 and 2002. Stroke volume and craniectomy area image analyses were performed with National Institutes of Health Image J software. Short-term outcome was measured with the Glasgow Outcome Scale. The requirement for second surgical decompression was also used as a measure of short-term outcome. Outcome 1 year after stroke was assessed with mailed self-report questionnaires to patients or providers with answers yielding information pertinent to the Barthel Index for physical disability, the Reintegration to Normal Living Index, and the Zung Depression Index. Univariate and multivariate logistic regression analyses were used to consider factors associated with outcome.

RESULTS:

Thirty-eight patients with large hemispheric infarcts (average volume, 407 cm3) were treated with hemicraniectomy during the study period. Thirty-two patients survived more than 1 year after surgery. Twenty patients responded to a questionnaire scoring late physical disability (Barthel Index), quality of life (Reintegration to Normal Living Index), and depression (Zung Depression Index). The average Barthel Index score was 67. Barthel Index score and ability to walk were strongly correlated with age but not time to surgery, volume of infarction, or craniectomy size. Patients exhibited moderate to severe decrements in quality of life and increased incidence of depression across all age groups. Reoperation, an indicator for early operative failure, was required in six patients. These patients were significantly younger and had significantly higher volumes of cerebral infarction.

CONCLUSION:

Hemicraniectomy is life-saving treatment for large middle cerebral artery infarction. Good functional outcomes can be obtained but are less likely in older patients. Younger patients with large-volume strokes may benefit from multiple decompressions, if necessary.
Radiosurgery for Cranial Base Chordomas and Chondrosarcomas
Authors: Krishnan Sunil , Foote Robert L. , Brown Paul D. , Pollock Bruce E. , Link Michael J. , Garces Yolanda I.
Published: March 2005

OBJECTIVE:

To evaluate the efficacy and toxicity of radiosurgery in the treatment of cranial base chordoma and chondrosarcoma.

METHODS:

We reviewed 29 patients with cranial base chordoma (n = 25) or chondrosarcoma (n = 4) who underwent stereotactic radiosurgery between September 1990 and December 2002. The median patient age was 45 years (range, 10–81 yr). Nineteen patients also had radiation therapy before or in conjunction with radiosurgery (median dose, 50.4 Gy). The median tumor volume was 14.4 cm3 (range, 0.6–65.1 cm3). The median tumor margin dose was 15 Gy (range, 10–20 Gy); the median maximum radiation dose was 30 Gy (range, 20–40 Gy). Median clinical and imaging follow-up periods were 4.8 and 4.5 years, respectively.

RESULTS:

Seven chordoma patients (28%) had tumor progression (in-field, n = 3; out-of-field, n = 4), whereas 18 had stable disease or tumor shrinkage. No patient with a chondroid chordoma had tumor enlargement. The actuarial tumor control rates were 89 and 32% at 2 and 5 years, respectively. All 4 patients with chondrosarcoma had tumor control. Clinically, 7 patients (24%) had improvement of pretreatment symptoms, 16 (55%) remained stable, and 6 (21%) worsened. Three patients with tumor progression died. Ten patients (34%) had radiation-related complications. Complications included cranial nerve deficits (n = 6), radiation necrosis (n = 5), and pituitary dysfunction (n = 3). Patients having radiosurgery alone had no toxicity.

CONCLUSION:

Cranial base chordomas and chondrosarcomas remain a formidable management challenge. Radiosurgery as an adjunct to surgical resection provides in-field tumor control for some patients, but radiation-related complications are relatively high, especially when radiosurgery is combined with fractionated radiation therapy.
Evaluation of the Stability of Small Ruptured Aneurysms with a Small Neck after Embolization with Guglielmi Detachable Coils: Correlation between Coil Packing Ratio and Coil Compaction
Authors: Kai Yutaka , Hamada Jun-ichiro , Morioka Motohiro , Yano Shigetoshi , Kuratsu Jun-ichi
Published: March 2005

OBJECTIVE:

Because it is difficult to predict the compaction of Guglielmi detachable coils (GDCs) after endovascular surgery for aneurysms, we studied the relationship between the coil packing ratio and compaction. Here, we propose a simple method for the preoperative estimation of coil compaction. Using follow-up angiograms, we studied the timing and degree of coil compaction in small terminal and side-wall aneurysms with narrow necks.

METHODS:

We studied 62 patients with acute ruptured intracranial aneurysms that were small (<10 mm), had a small neck (<4 mm), and were coil embolized with GDC-10s. The aneurysmal volume was calculated using the equation V = 4/3π(a/2) × (b/2) × (c/2), where a, b, and c are the aneurysmal height, length, and width in millimeters, respectively. The coil volume was calculated using the equation V = π(p/2)2 × l × 10, where p represents the GDC-10 coil diameter (0.25 mm) and l is the coil length. We recorded the maximum prospective coil length, L, as that corresponding with the volume of packed coils occupying 30% of the aneurysmal volume. Therefore, L was calculated as L (cm) = 0.3 × a × b × c, and the coil packing ratio was expressed as packed coil length/L × 100. Angiographic follow-up studies were generally performed at 3 months and 1 and 2 years after endovascular surgery. We considered coil compaction exceeding 2 mm as major compaction and recorded minor compaction when it was less than 2 mm of the empty reappeared space in the embolized aneurysm. Aneurysmal location was recorded as terminal or side wall.

RESULTS:

Of the 62 patients, 16 (25.8%) manifested angiographic coil compaction (10 minor and 6 major compactions); the mean coil packing ratio was 51.9 ± 13.4%. The mean coil packing ratio in the other 46 patients was 80.5 ± 20.2%, and the difference was statistically significant (P < 0.01). In all 6 patients with major compaction, the mean packing ratio was less than 50% and all underwent re-embolization after a mean of 24.9 ± 1.1 months. The 10 patients with minor compaction were conservatively treated, and the degree of compaction did not change during a mean period of 24 months. We detected 93.8% of the compactions within 12 months of coil placement. The aneurysm was of the terminal type in 5 of the 6 patients with major coil compaction.

CONCLUSION:

In patients who underwent embolization with GDC-10s of aneurysms that were small and had a small neck, the optimal coil packing ratio could be identified with the formula 0.3 × a × b × c. The probability of coil compaction was significantly higher when the coil packing ratio was less than 50%. To detect coil compaction after embolization, follow-up angiograms must be examined regularly for at least 12 months. To detect major coil compaction in patients with terminal type aneurysms, angiographic follow-up should not be shorter than 24 months.