bluuebunny/crossref_metadata_2025 huggingface dataset:
Using journal writing to enhance reflective practice
Authors: Boud David
Published: August 2002

Journals promote reflection on experience. This chapter examines features of journal writing that aid reflective practice and circumstances inhibiting their use for this purpose.
Uses and benefits of journal writing
Authors: Hiemstra Roger
Published: August 2002

Adult educators should consider the benefits of journal writing in terms of their own learning and professional development.
Women, journal writing, and the reflective process
Authors: Peterson Elizabeth A. , Jones Ann M.
Published: August 2002

Women's journals are a unique treasure that provide a glimpse into the lives of individuals whose voices otherwise would not have been heard. Journals continue to be a source of inspiration and revelation for the women who write them and those who read them.
Context‐Based Adult Learning
Authors: Hansman Catherine A.
Published: August 2002

Adult learning takes place in context where tools and the context intersect with interaction among people.
Dissociation, memory and suggestibility in adults and children
Authors: Eisen Mitchell L. , Lynn Steven J.
Published: August 2002

The present article reviews research and theory related to dissociation, memory, and suggestibility in adults and children. We examine various manifestations of dissociation (e.g. trait versus state accounts of dissociation, pathological versus non‐pathological dissociation), the different ways that memory and suggestibility are defined and measured across studies, and the extent to which dissociation is related to suggestibility as a function of the definition and measurement of relevant constructs. Finally, we examine the relationship between dissociation and children's resistance to misinformation, provide a critical review of the strengths and limitations of the extant literature, and suggest directions for future research and theoretical developments in the field. Copyright © 2001 John Wiley & Sons, Ltd.
Central venous catheter complications in sickle cell disease
Authors: Jeng Michael R. , Feusner James , Skibola Christine , Vichinsky Elliott
Published: August 2002

A review of patients with sickle cell disease (SCD) and central venous catheters (CVCs) was performed to evaluate the frequency of catheter complications (infections, thrombotic events, and premature CVC removal. Fifteen evaluable patients were identified during our review of a 7.5‐year period. The median age was 18 years (range, 1.5–30 years); 14 were African American, and 1 was Latino; 5 were male, and 10 were female. Forty‐one CVCs were placed (36 Mediport and 5 Broviac catheters) for a total of 12,120 CVC days. We observed a median of 2 CVCs per patient (range, 1–8 CVCs per patient) with 67 discrete episodes of CVC‐associated infection (range, 0–18 per patient) involving 10 patients. The rate of CVC‐associated infection for patients with SCD at our institution was 5.5 infections per 1,000 CVC days; this rate was significantly higher than the rate of CVC‐associated infection in our patients with cancer (P < 0.001). We also determined that the rate of CVC‐associated thrombosis was 0.99 events per 1,000 CVC days and involved 33% of the patients with SCD; the rate of premature CVC removal was 3.15 per 1,000 CVC days, and 78% of CVCs were removed prematurely. We conclude that patients with SCD are at high risk for CVC‐related complications, and improved care and close monitoring of CVCs should be encouraged to decrease morbidity in these chronically ill patients. Am. J. Hematol. 69:103–108, 2002. © 2002 Wiley‐Liss, Inc.
Clinical severe hepatic venoocclusive disease during induction treatment of acute monoblastic leukemia managed with defibrotide
Authors: Bairey Osnat , Kirgner Ilia , Yakobi Moshe , Hamdan Ashraf , Ben‐Ari Ziv , Shaklai Mati
Published: August 2002

Hepatic venoocclusive disease (VOD) is the most common complication of cytoreductive therapy used for stem cell transplantation, but it is rarely encountered during induction treatment of acute leukemia. We describe a patient in whom severe clinical VOD developed shortly after induction treatment for acute monoblastic leukemia. Administration of intravenous defibrotide for 19 days induced complete resolution of the VOD. Further consolidation treatment was resumed including high‐dose cytosine arabinoside without further complications. Am. J. Hematol. 69:281–284, 2002. © 2002 Wiley‐Liss, Inc.
Successful treatment of high titer inhibitors in mild hemophilia A with avoidance of factor VIII and immunosuppressive therapy
Authors: Robbins Daniel , Kulkarni Roshni , Gera Renuka , Scott‐Emuakpor Ajovi B. , Bosma Kathy , Penner John A.
Published: August 2002

We describe two patients with mild hemophilia A (MHA) who developed high titer inhibitor (HTI) following intensive recombinant factor VIII (rFVIII) concentrate replacement for surgery and trauma. Intranasal desmopressin was instituted shortly following immunosuppressive therapy (IST) and activated prothrombin complex concentrate (APCC) in one case, and following APCC alone in the second case. Avoidance of factor VIII (FVIII) coupled with intranasal desmopressin prophylaxis three times a week resulted in undetectable inhibitor levels. Both patients have had no further bleeding episodes and have been maintained on desmopressin prophylaxis prior to activity for the past 2 to 3 years. Recombinant factor VIIa (rFVIIa) was used successfully prior to a second surgery in one patient without complication. Am. J. Hematol. 68:184–188, 2001.© 2001 Wiley‐Liss, Inc.
Time dependent memory decay
Authors: Jenkins Paul , Earle‐Richardson Giulia , Slingerland David Tucker , May John
Published: August 2002

Background

To estimate the rate of time dependent memory decay, injury rates from three independent studies were compared.

Methods

The studies asked subjects to recall injuries during the previous 2 months, 12 months, or 10 years.

Results

The annual injury rates obtained were 108/1,000, 66/1,000, and 19/1,000, respectively. These rates are all significantly different from one another at the 0.05 level.

Conclusions

Important methodological and demographic differences between the studies, such as those involving age, injury severity, and seasonality, were ruled out as causes of these differences. Results found in the literature for other studies are compared and contrasted. These data suggest that recall periods of greater than 2 months are likely to significantly underestimate injury rates. Am. J. Ind. Med. 41:98–101, 2002. © 2002 Wiley‐Liss, Inc.
A prospective study of computer users: I. Study design and incidence of musculoskeletal symptoms and disorders
Authors: Gerr Fredric , Marcus Michele , Ensor Cindy , Kleinbaum David , Cohen Susan , Edwards Alicia , Gentry Eileen , Ortiz Daniel J. , Monteilh Carolyn
Published: August 2002

Background

A prospective study of computer users was performed to determine the occurrence of and evaluate risk factors for neck or shoulder (N/S) and hand or arm (H/A) musculoskeletal symptoms (MSS) and disorders (MSD).

Methods

Individuals (n = 632) newly hired into jobs requiring  ≥ 15 hr/week of computer use were followed for up to 3 years. At study entry, workstation dimensions and worker postures were measured and medical and psychosocial risk factors were assessed. Daily diaries were used to document work practices and incident MSS. Those reporting MSS were examined for specific MSD. Incidence rates of MSS and MSD were estimated with survival analysis. Cox regression models were used to evaluate associations between participant characteristics at entry and MSS and MSD.

Results

The annual incidence of N/S MSS was 58 cases/100 person‐years and of N/S MSD was 35 cases/100 person‐years. The most common N/S MSD was somatic pain syndrome. The annual incidence of H/A MSS was 39 cases/100 person‐years and of H/A MSD was 21 cases/100 person‐years. The most common H/A disorder was deQuervain's tendonitis. Forty‐six percent of N/S and 32% of H/A MSS occurred during the first month of follow‐up. Gender, age, ethnicity, and prior history of N/S pain were associated with N/S MSS and MSD. Gender, prior history of H/A pain, prior computer use, and children at home were associated with either H/A MSS or MSD.

Conclusions

H/A and N/S MSS and MSD were common among computer users. More than 50% of computer users reported MSS during the first year after starting a new job. Am. J. Ind. Med. 41:221–235, 2002. © 2002 Wiley‐Liss, Inc.
Molecular characterization of a ring chromosome 16 from a patient with bilateral cataracts
Authors: He Weigong , Tuck‐Muller Cathy M. , Martínez José E. , Li Shibo , Rowley Ewellonda R. , Wertelecki Wladimir
Published: August 2002

A four‐month‐old white female, who was referred to us for genetic evaluation because of severe developmental delay, dysmorphic features, and bilateral cataracts, was found by routine cytogenetic analysis to have ring chromosome 16 in almost all cells analyzed. Ring chromosome 16 was confirmed and further delineated by fluorescence in situ hybridization (FISH). Breakpoints between loci D16S521 and KG8 on the short arm and D16S3121 and D16S303 on the long arm of chromosome 16 were determined by polymerase chain reaction (PCR) analysis. The deleted chromosome was of maternal origin. To our knowledge, this is the first case of ring chromosome 16 associated with bilateral cataracts. Comparison of previously reported cases with deletion of chromosome 16 and our case suggests the presence of cataract locus within 1 Mb of the terminus of 16q. © 2001 Wiley‐Liss, Inc.
Association of DRD4 in children with ADHD and comorbid conduct problems
Authors: Holmes Jane , Payton Antony , Barrett Jennifer , Harrington Richard , McGuffin Peter , Owen Michael , Ollier William , Worthington Jane , Gill Michael , Kirley Aiveen , Hawi Ziarih , Fitzgerald Michael , Asherson Philip , Curran Sarah , Mill John , Gould Alison , Taylor Eric , Kent Lyndsey , Craddock Nick , Thapar Anita
Published: August 2002

Recent family and twin study findings suggest that ADHD when comorbid with conduct problems may represent a particularly familial and heritable form of ADHD. Although several independent groups have shown association between the DRD4 7 repeat allele and ADHD, others have failed to replicate this finding. Previous TDT analyses of UK and Eire samples had also been negative. We set out to further examine the role of DRD4 but selecting a subgroup of children with ADHD and comorbid conduct problems. Families were recruited from Manchester, Ireland, Birmingham and London clinics. From these, 67 children who fulfilled diagnostic criteria for ADHD and who displayed conduct disorder symptoms were selected. TDT analysis, which had previously yielded negative results for the total sample, showed evidence of association between DRD4 and “ADHD with conduct problems” (7 repeat allele‐24 transmissions, 13 non‐transmissions; one‐tailed P = 0.05). These results provide further support for the role of DRD4 in ADHD. Furthermore, these results when considered together with family and twin study findings, suggest that those children with ADHD and comorbid conduct problems may be particularly informative for molecular genetic studies of ADHD. Further work is needed to examine these phenotype issues. © 2002 Wiley‐Liss, Inc.
Endophenotypes in bipolar disorder†
Authors: Lenox Robert H. , Gould Todd D. , Manji Husseini K.
Published: August 2002

The search for genes in bipolar disorder has provided numerous genetic loci that have been linked to susceptibility to developing the disorder. However, because of the genetic heterogeneity inherent in bipolar disorder, additional strategies may need to be employed to fully dissect the genetic underpinnings. One such strategy involves reducing complex behaviors into their component parts (endophenotypes). Abnormal neurophysiological, biochemical, endocrinological, neuroanatomical, cognitive, and neuropsychological findings are characteristics that often accompany psychiatric illness. It is possible that some of these may eventually be useful in subdefining complex genetic disorders, allowing for improvements in diagnostic assessment, genetic linkage studies, and development of animal models. Findings in patients with bipolar disorder that may eventually be useful as endophenotypes include abnormal regulation of circadian rhythms (the sleep/wake cycle, hormonal rhythms, etc.), response to sleep deprivation, P300 event‐related potentials, behavioral responses to psychostimulants and other medications, response to cholinergics, increase in white matter hyperintensities (WHIs), and biochemical observations in peripheral mononuclear cells. Targeting circadian rhythm abnormalities may be a particularly useful strategy because circadian cycles appear to be an inherent evolutionarily conserved function in all organisms and have been implicated in the pathophysiology of bipolar disorder. Furthermore, lithium has been shown to regulate circadian cycles in diverse species, including humans, possibly through inhibition of glycogen synthase kinase 3‐β (GSK‐3β), a known target of lithium. Published 2002 Wiley‐Liss, Inc.
Apparent replication of suggestive linkage on chromosome 16 in the NIMH genetics initiative bipolar pedigrees
Authors: Dick Danielle M. , Foroud Tatiana , Edenberg Howard J. , Miller Marvin , Bowman Elizabeth , Rau N. Leela , DePaulo J. Raymond , McInnis Melvin , Gershon Elliot , McMahon Francis , Rice John P. , Bierut Laura J. , Reich Theodore , Nurnberger John
Published: August 2002

Analyses of a replication sample of families collected as part of the National Institute of Mental Health (NIMH) Genetics Initiative for bipolar disorder provide further evidence for linkage to a region of chromosome 16. Families who had a bipolar I (BPI) proband and at least one BPI or schizoaffective, bipolar type (SABP) first‐degree relative were ascertained for the purpose of identifying genes involved in bipolar affective disorder. A series of hierarchical models of affected status was used in linkage analyses. Initial genetic analyses of chromosomes 3, 5, 15, 16, 17, and 22, completed at Indiana University in 540 subjects from 97 families, suggested evidence of linkage to chromosomes 5, 16, and 22 [Edenberg et al., 1997: Am J Med Genet 74:238–246]. Genotyping was subsequently performed on these chromosomes in a replication sample of 353 individuals from 56 families. Nonparametric linkage analyses were performed using both affected relative and sibling pair methods. Analyses in the new sample on chromosome 16, using the broadest model of affected status, corroborate previously reported suggestive linkage to the marker D16S2619. Combining the initial and replication samples further increased the evidence of linkage to this region, with a peak lod score of 2.8. © 2002 Wiley‐Liss, Inc.
DRD4 exon 3 variants associated with delusional symptomatology in major psychoses: A study on 2,011 affected subjects
Authors: Serretti Alessandro , Lilli Roberta , Lorenzi Cristina , Lattuada Enrico , Smeraldi Enrico
Published: August 2002

We previously reported an association of DRD4 exon3 long allele variants with delusional symptomatology independently from diagnoses. The aim of this investigation was to study DRD4 in major psychoses and to test the association in a larger sample. We studied 2,011 inpatients affected by bipolar disorder (n = 811), major depressive disorder (n = 635), schizophrenia (n = 419), delusional disorder (n = 104), psychotic disorder not otherwise specified (n = 42), and 601 healthy controls. A subsample of 1,264 patients were evaluated using the OPCRIT checklist and differences of symptomatology factor scores among genetic variants were assessed using one‐way analysis of variance (ANOVA). DRD4 allele and genotype frequencies in bipolars, schizophrenics, delusionals, and psychotic NOS were not significantly different from controls; major depressives showed a trend toward an excess of DRD4*Short and DRD4*Short/Short variants versus controls. The ANOVA on factor scores in the whole subsample of 1,264 subjects showed a significant difference on delusion factor in allele analysis (P = 0.007), and in genotype one (P = 0.018), with DRD4*Long containing variants associated with severe symptomatology. The analysis in the replication subjects only (n = 803) showed a trend in the same direction, though not reaching the significance level. This analysis in an enlarged sample suggests that DRD4*Long alleles exert a small but significant influence on the delusional symptomatology in subjects affected by major psychoses. © 2001 Wiley‐Liss, Inc.
Attention‐deficit hyperactivity disorder: A study of association with both the dopamine transporter gene and the dopamine D4 receptor gene
Authors: Roman Tatiana , Schmitz Marcelo , Polanczyk Guilherme , Eizirik Mariana , Rohde Luis A. , Hutz Mara H.
Published: August 2002

Attention‐deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders of childhood. The role of genetic factors in its etiology is strongly supported by family, adoption, and twin studies. Several investigations have reported associations between ADHD and both the 7‐repeat allele of the 48 bp VNTR at the DRD4 gene and the 10‐repeat allele of the 40 bp VNTR at the DAT1 gene, but the results have been inconsistent. A sample of 81 Brazilian ADHD children and adolescents and their parents were screened for these DRD4 and DAT1 VNTRs. An excess of the DRD4 7‐repeat allele was observed when both ADHD probands and their parents were compared with an ethnically matched control sample (chi‐square = 11.55, P = 0.03; chi‐square = 12.17, P = 0.03, respectively). However, haplotype relative risk (HRR) analysis showed no preferential transmission of the DRD4 7‐repeat allele. No evidence of association with the DAT1 polymorphism was detected by both approaches. Nevertheless, an interaction effect of both genes on ADHD hyperactive/impulsive dimension was observed (F = 4.68; P = 0.03). These results add to the group of studies that together suggest a small effect of these genes in the susceptibility to ADHD. © 2001 Wiley‐Liss, Inc.
Lack of association between the tryptophan hydroxylase gene A218C polymorphism and attention‐deficit hyperactivity disorder in Chinese Han population
Authors: Tang Guomei , Ren Daming , Xin Rener , Qian Yiping , Wang Dongyang , Jiang Sanduo
Published: August 2002

Previous studies have suggested that the serotonergic (5‐HT) system might be involved in the development of Attention‐deficit hyperactivity disorder (ADHD). ADHD is frequently characterized by aggressive and impulsive behavior, a major symptom associated with reduction in serotonergic function. The tryptophan hydroxylase (TPH) gene is a reasonable candidate for ADHD because it encodes the rate‐limiting enzyme in the process of 5‐HT biosynthesis. In this study, we examined the relationship between the A218C polymorphism in TPH gene and ADHD. Sixty‐nine ADHD patients and their biological parents were investigated. The A218C polymorphism in intron 7 of TPH gene was detected by PCR‐RFLP method. No allele or genotype concerned with this A218C polymorphism was found to be associated with ADHD when analyzed with the haplotype relative risk method. Therefore, our data indicate that the TPH gene A218C polymorphism may not be a susceptibility factor of ADHD in the Chinese Han population. © 2001 Wiley‐Liss, Inc.
Genetic, geographic, and linguistic variation among South American Indians: Possible sex influence
Authors: Fagundes Nelson J.R. , Bonatto S.L. , Callegari‐Jacques S.M. , Salzano F.M.
Published: August 2002

To better understand the relationship between genetic variability, geographical distance, and linguistic affiliation in South Amerinds, and to elucidate whether the migration rate is the same for both sexes, spatial autocorrelation, Mantel's test, and FST analyses were performed in four sets of populations and alleles (group 1: 48 populations, 12 alleles; group 2: 16 (all belonging to the Tupi linguistic group) and 12; group 3: 21 and 17; and group 4: 28 and 4 haplotypes). Groups 1–3 included blood group and protein (i.e., serum protein, red cell enzymes, and immunoglobulin systems), while group 4 was concerned with mitochondrial DNA (mtDNA) only. The latter set was also subjected to a molecular analysis of variance (AMOVA) evaluation. The frequencies of statistically significant correlograms were lower than those obtained in other populations when the blood groups and protein systems were considered, but 3 of the 4 mtDNA haplogroups gave suggestions of population structure. The variability in this organelle is also significantly correlated with language when geography is held constant. Migration per generation is generally low, but higher estimates were obtained for females. The AMOVA results suggest that populations whose members speak the same language are genetically homogeneous and may be viewed as the ultimate evolutionary unit at this level of analysis. Am J Phys Anthropol 117:68–78, 2002. © 2002 Wiley‐Liss, Inc.
Evidence of probable scurvy in subadults from archeological sites in North America
Authors: Ortner Donald J. , Butler Whitney , Cafarella Jessica , Milligan Lauren
Published: August 2002

The authors surveyed subadult human skeletons from Native American archeological sites in the United States for evidence of skeletal lesions associated with scurvy. Geographic regions surveyed include the Midatlantic area, the Southeast (Florida), the Southwest, and the Plains. The prevalence of probable subadult scurvy ranged from zero in the Plains samples to 38% in a small sample from Florida. These data indicate the likelihood that scurvy was a significant childhood disease in many Native American groups. Reasons for variation in prevalence remain speculative but include regional and seasonal variation in food types and abundance, cultural patterns of storage and utilization, periodic food shortages, and the relative importance of corn in the diet. These factors are part of a nutritional complex that is related to disease prevalence which can be studied through evidence seen in archeological human remains. Am J Phys Anthropol 114:343–351, 2001. © 2001 Wiley‐Liss, Inc.
Cranial deformation in a subadult sample from Değirmentepe (Chalcolithic, Turkey)
Authors: Özbek Metin
Published: August 2002

Human skeletal remains from the Chalcolithic period of Değirmentepe, Turkey, near the Euphrates River, display artificial cranial deformation of the circular type. Human skeletal remains belonging to 31 individual have been dated to the Chalcolithic period (second half of the fifth millennium BC, uncalibrated). The remains include foetuses, infants, children and juveniles; but no adult skeletons. Either the adults were buried elsewhere or flooding of the Euphrates dragged the adult remains away. Artificial cranial deformation was observed in 13 of the 31 subadults ranging in age from 1 month to 13–14 years. Değirmentepe villagers might have used one or two circular constricting bands with the intent of producing artificial head deformation. As far as Anatolia and the Near Eastern region is concerned, the widespread use of circular head deformation may be an indication of longer‐distance trade and more need for ethnic markers. Am J Phys Anthropol 115:238–244, 2001. © 2001 Wiley‐Liss, Inc.
Effect of therapeutic ionizing radiation on the human brain
Authors: Steen R. Grant , Spence David , Wu Shengjie , Xiong Xiaoping , Kun Larry E. , Merchant Thomas E.
Published: August 2002

We test a hypothesis that fractionated radiation therapy within a therapeutic dose range is associated with a dose‐related change in normal brain, detectable by quantitative magnetic resonance imaging. A total of 33 patients were examined by quantitative magnetic resonance imaging to measure brain tissue spin‐lattice relaxation time (T1) before treatment, and at various times during and after radiation therapy. A T1 map was generated at each time point, and radiation therapy isodose contours were superimposed on the corresponding segmented T1 map. Changes in white matter and gray matter T1 were analyzed as a function of radiation therapy dose and time since treatment, controlling for patient age and tumor site. In white matter, a dose level of more than 20Gy was associated with a dose‐dependent decrease in T1 over time, which became significant 6 months after treatment. There was no significant change in T1 of gray matter over time, at radiation therapy doses of less than 60Gy. However, GM in close proximity to the tumor had a lower T1 before therapy. Our results represent the first radiation dose‐response data derived from pediatric brain in vivo. These findings confirm that white matter is more vulnerable to radiation‐induced change than is gray matter, and suggest that T1 mapping is sensitive to radiation‐related changes over a broad dose range (20 to 60Gy). Human white matter T1 is not sensitive to radiation therapy of less than 20Gy, and gray matter T1 is unchanged over the dose range used to treat human brain tumor. The reduction of gray matter T1 near the tumor could result from compression of cortical parenchyma near the growing tumor mass, or from tumor cell invasion directly into the parenchyma. If brain T1 is a surrogate for radiation effect, reducing the volume of normal white matter receiving more than 20Gy could be an important treatment planning goal.
Compensating for central nervous system dysmyelination: Females with a proteolipid protein gene duplication and sustained clinical improvement
Authors: Inoue Ken , Tanaka Hajime , Scaglia Fernando , Araki Akiko , Shaffer Lisa G. , Lupski James R.
Published: August 2002

A submicroscopic duplication that contains the entire proteolipid protein gene is the major cause of Pelizaeus‐Merzbacher disease, an X‐linked central nervous system dysmyelinating disorder. Previous studies have demonstrated that carrier females for the duplication are usually asymptomatic. We describe 2 unrelated female patients who present with mild Pelizaeus‐Merzbacher disease or spastic paraplegia. In 1 patient, clinical features as well as cranial magnetic resonance imaging and brainstem auditory evoked potential results have improved dramatically over a 10‐year period. The other patient, who presented with spastic diplegia and was initially diagnosed with cerebral palsy, has also shown clinical improvement. Interphase fluorescent in situ hybridization identified a proteolipid protein gene duplication in both patients. Interphase fluorescent in situ hybridization analyses of the family members indicated that the duplication in both patients occurred as de novo events. Neither skewing of X inactivation in the peripheral lymphocytes nor proteolipid protein gene coding alterations were identified in either patient. These findings indicate that, occasionally, females with a proteolipid protein gene duplication can manifest an early‐onset neurological phenotype. We hypothesize that the remarkable clinical improvement is a result of myelin compensation by oligodendrocytes expressing one copy of proteolipid protein gene secondary to selection for a favorable X inactivation pattern. These findings indicate plasticity of oligodendrocytes in the formation of central nervous system myelin and suggest a potential role for stem cell transplantation therapies.
Factors that influence peripheral nerve regeneration: An electrophysiological study of the monkey median nerve
Authors: Krarup Christian , Archibald Simon J. , Madison Roger D.
Published: August 2002

Regeneration in the peripheral nervous system is often incomplete though it is uncertain which factors, such as the type and extent of the injury or the method or timing of repair, determine the degree of functional recovery. Serial electrophysiological techniques were used to follow recovery from median nerve lesions (n = 46) in nonhuman primates over 3 to 4 years, a time span comparable with such lesions in humans. Nerve gap distances of 5, 20, or 50mm were repaired with nerve grafts or collagen‐based nerve guide tubes, and three electrophysiological outcome measures were followed: (1) compound muscle action potentials in the abductor pollicis brevis muscle, (2) the number and size of motor units in reinnervated muscle, and (3) compound sensory action potentials from digital nerve. A statistical model was used to assess the influence of three variables (repair type, nerve gap distance, and time to earliest muscle reinnervation) on the final recovery of the outcome measures. Nerve gap distance and the repair type, individually and concertedly, strongly influenced the time to earliest muscle reinnervation, and only time to reinnervation was significant when all three variables were included as outcome predictors. Thus, nerve gap distance and repair type exert their influence through time to muscle reinnervation. These findings emphasize that factors that control early axonal outgrowth influence the final level of recovery attained years later. They also highlight that a time window exists within which axons must grow through the distal nerve stump in order for recovery after nerve lesions to be optimal. Future work should focus on interventions that may accelerate the growth of axons from the lesion site into the distal nerve stump.
Novel heteroplasmic mtDNA mutation in a family with heterogeneous clinical presentations
Authors: Corona P. , Lamantea E. , Greco M. , Carrara F. , Agostino A. , Guidetti D. , Dotti M. T. , Mariotti C. , Zeviani M.
Published: August 2002

The protean manifestations of a novel maternally inherited point mutation of the mitochondrial genome are reported. The proband showed isolated, spastic paraparesis. A brother, who had suffered from a multisystem progressive disorder, ultimately died of cardiomyopathy. Another brother is healthy. The proband's mother showed truncal ataxia, dysarthria, severe hearing loss, mental regression, ptosis, ophthalmoparesis, distal cyclones, and diabetes mellitus. A muscle biopsy performed in the proband failed to show the morphological abnormalities typical of mitochondrial disorders; the activities of respiratory chain complexes were normal. However, complex I and IV activities were low in the muscle homogenate of the affected mother and brother. Sequence analysis of mtDNA showed a heteroplasmic mutation of the tRNAIle gene (G4284A). The mutation load was approximately 55%, 80%, and 90% in the muscle mtDNA of the proband, his mother, and his affected brother, respectively. Mutation was undetected in the healthy brother, as well as in 100 control samples. Several cybrid clones containing homoplasmic mutant mtDNA from the proband showed significant reductions of complex IV activity and maximum oxygen consumption rate, compared with homoplasmic wild‐type clones derived from the same subject.
Destruction of neurons by cytotoxic T cells: A new pathogenic mechanism in rasmussen's encephalitis
Authors: Bien Christian G. , Bauer Jan , Deckwerth Thomas L. , Wiendl Heinz , Deckert Martina , Wiestler Otmar D. , Schramm Johannes , Elger Christian E. , Lassmann Hans
Published: August 2002

Rasmussen's encephalitis is a progressive epileptic disorder characterized by unihemispheric lymphocytic infiltrates, microglial nodules, and neuronal loss leading to the destruction of the affected hemisphere. In this study, immunohistochemical evaluation of specimens from 11 patients revealed lymphocytic infiltrates that consisted mainly of CD3+CD8+ T cells. Of these cells, 7.0% lay in direct apposition to MHC class I+ neurons. Confocal laser microscopy revealed that these lymphocytes contained granzyme B in a polar orientation toward these perikarya. Single neurons underwent apoptosis. These findings indicate that a T‐cell–mediated cytotoxic reaction induces neuronal death in Rasmussen's encephalitis. This study directly shows, for what we believe is the first time, that a cytotoxic T‐cell mechanism contributes to loss of neurons in human brain disease.
Antibody‐mediated suppression of Vβ5.2/5.3+ T cells in multiple sclerosis: Results from an MRI‐monitored phase II clinical trial
Authors: Killestein Joep , Olsson Tomas , Wallström Erik , Svenningsson Anders , Khademi Mohsen , Blumhardt Lance D. , Fagius Jan , Hillert Jan , Landtblom Anne‐Marie , Edenius Charlotte , Årfors Leopold , Barkhof Frederik , Polman Chris H.
Published: August 2002

The objective of this study was to evaluate the safety and efficacy of the humanized antibody ATM‐027 in a baseline versus treatment magnetic resonance imaging‐monitored study. Expansion of Vβ5.2/5.3+ T cells has been demonstrated in the peripheral blood, cerebrospinal fluid, and brain lesions of MS patients. In a phase I study, ATM‐027 depleted these cells in peripheral blood and, in parallel, T‐cell MBP reactivity and IFN‐γ expression were reduced. We studied 59 patients with relapsing‐remitting MS (47 on ATM‐027 and 12 on placebo) stratified for HLA‐DR2 status. Monthly intravenous injections were given for 6 months. Individual dose titration was employed to obtain depletion of the target T‐cell level and downregulation of antigen receptor density as monitored by flow cytometry. Five monthly magnetic resonance imaging scans were performed before treatment to establish baseline activity, six during treatment, and three during follow‐up. Additional immunological assessments were performed to elucidate the mechanism of action of ATM‐027. The treatment was safe and well tolerated, inducing consistent suppression of the target cell population. During run‐in, active lesions were found in 78.7% (37/47) of patients treated with ATM‐027. During treatment, the median number of lesions was reduced by 33% (p = 0.13) independent of DR2 status. The corresponding volume of enhancement was 221 mm3 at baseline, with a reduction of 10% during treatment. Decreased numbers of cells expressing interferon‐γ messenger RNA, and decreased T‐cell reactivity to several myelin antigens were found in ATM‐027 treated patients. In conclusion, consistent suppression of Vβ 5.2/5.3+ T cells was achieved. However, the effect size on magnetic resonance imaging was considerably less than the targeted 60%.
Age‐related disability in multiple sclerosis
Authors: Trojano Maria , Liguori Maria , Bosco Zimatore Giovanni , Bugarini Roberto , Avolio Carlo , Paolicelli Damiano , Giuliani Fabrizio , De Robertis Francesca , Marrosu Maria Giovanna , Livrea Paolo
Published: August 2002

There is evidence that the clinical course of multiple sclerosis is age related. The present study evaluated the relationship between age and rate of disability progression in a large hospital‐based cohort of definite cases of multiple sclerosis (n= 1,463). Patients were followed every 6 to 12 months for a total period of observation of 11,387.8 person‐years. Expanded Disability Status Scale scores increased significantly with increasing current age and longer duration of disease (p=0.007). Median times to reach Expanded Disability Status Scale scores of 4.0 and 6.0, assessed using an extended Kaplan–Meier method with age as a categorical time‐varying covariate, were significantly longer among patients aged 20 to 35 years compared with patients aged 36 to 50 and 51 to 65 years (p < 0.0001). Significant associations were observed between mean Expanded Disability Status Scale scores and age at disease onset, current age, and the interaction of age at disease onset and current age (p < 0.001). Current age had a greater effect (59% of variability in the model) on disease severity than did age at disease onset. Furthermore, a multiplicative effect on Expanded Disability Status Scale score was observed for age at disease onset and current age combined, indicating a faster rate of disease progression in older patients. In conclusion, the results of the current study demonstrate the impact of age on rate of disability progression in multiple sclerosis and suggest that an age‐adjusted progression index may be a more relevant criterion for defining differences between multiple sclerosis groups.
Human herpesvirus 6 encephalitis associated with hypersensitivity syndrome
Authors: Fujino Yasuhiro , Nakajima Masashi , Inoue Hirosato , Kusuhara Tomohiko , Yamada Tatsuo
Published: August 2002

Hypersensitivity syndrome, a serious systematic reaction to a limited number of drugs, is associated with the reactivation of human herpesvirus 6. A 56‐year‐old man developed acute limbic encephalitis followed by multiple organ failure during the course of toxic dermatitis induced by aromatic anticonvulsants. The clinical features of skin eruptions, high fever, eosinophilia, and atypical lymphocytosis were compatible with drug hypersensitivity syndrome. The patient showed seroconversion for human herpesvirus 6, and polymerase chain reaction detected human herpesvirus 6 DNA in the cerebrospinal fluid. To our knowledge, this is the first report of human herpesvirus 6 encephalitis associated with hypersensitivity syndrome.
Relapsed and late‐onset Nipah encephalitis
Authors: Tan Chong Tin , Goh Khean Jin , Wong Kum Thong , Sarji Sazilah Ahmad , Chua Kaw Bing , Chew Nee Kong , Murugasu Paramsothy , Loh Yet Lin , Chong Heng Thay , Tan Kay Sin , Thayaparan Tarmizi , Kumar Shalini , Jusoh Mohd Rani
Published: August 2002

An outbreak of infection with the Nipah virus, a novel paramyxovirus, occurred among pig farmers between September 1998 and June 1999 in Malaysia, involving 265 patients with 105 fatalities. This is a follow‐up study 24 months after the outbreak. Twelve survivors (7.5%) of acute encephalitis had recurrent neurological disease (relapsed encephalitis). Of those who initially had acute nonencephalitic or asymptomatic infection, 10 patients (3.4%) had late‐onset encephalitis. The mean interval between the first neurological episode and the time of initial infection was 8.4 months. Three patients had a second neurological episode. The onset of the relapsed or late‐onset encephalitis was usually acute. Common clinical features were fever, headache, seizures, and focal neurological signs. Four of the 22 relapsed and late‐onset encephalitis patients (18%) died. Magnetic resonance imaging typically showed patchy areas of confluent cortical lesions. Serial single‐photon emission computed tomography showed the evolution of focal hyperperfusion to hypoperfusion in the corresponding areas. Necropsy of 2 patients showed changes of focal encephalitis with positive immunolocalization for Nipah virus antigens but no evidence of perivenous demyelination. We concluded that a unique relapsing and remitting encephalitis or late‐onset encephalitis may result as a complication of persistent Nipah virus infection in the central nervous system.
Low cerebrospinal fluid hypocretin (orexin) and altered energy homeostasis in human narcolepsy
Authors: Nishino Seiji , Ripley Beth , Overeem Sebastiaan , Nevsimalova Sona , Lammers Gert Jan , Vankova Jitka , Okun Michele , Rogers William , Brooks Stephen , Mignot Emmanuel
Published: August 2002

Hypocretins (orexins) are hypothalamic neuropeptides involved in sleep and energy homeostasis. Hypocretin mutations produce narcolepsy in animal models. In humans, narcolepsy is rarely due to hypocretin mutations, but this system is deficient in the cerebrospinal fluid (CSF) and brain of a small number of patients. A recent study also indicates increased body mass index (BMI) in narcolepsy. The sensitivity of low CSF hypocretin was examined in 38 successive narcolepsy–cataplexy cases [36 human leukocyte antigen (HLA)‐DQB1*0602‐positive] and 34 matched controls (15 controls and 19 neurological patients). BMI and CSF leptin levels were also measured. Hypocretin‐1 was measurable (169 to 376pg/ml) in all controls. Levels were unaffected by freezing/thawing or prolonged storage and did not display any concentration gradient. Hypocretin‐1 was dramatically decreased (<100pg/ml) in 32 of 38 patients (all HLA‐positive). Four patients had normal levels (2 HLA‐negative). Two HLA‐positive patients had high levels (609 and 637pg/ml). CSF leptin and adjusted BMI were significantly higher in patients versus controls. We conclude that the hypocretin ligand is deficient in most cases of human narcolepsy, providing possible diagnostic applications. Increased BMI and leptin indicate altered energy homeostasis. Sleep and energy metabolism are likely to be functionally connected through the hypocretin system.
Unexpected regioselectivity in the palladium‐catalyzed reaction of silacyclobutanes with aryl iodides
Authors: Tanaka Yoshifumi , Nishigaki Atsushi , Kimura Yutaka , Yamashita Masakazu
Published: August 2002

The reaction of aryl iodides with 1,1‐diphenyl‐silacyclobutane in the presence of a catalytic amount of Pd(PPh3)4 affords unexpected ring‐opening adducts, 1‐ and 2‐propenyl(triaryl)‐silanes, in good yields. On the other hand, the PdCl2(PhCN)2‐catalyzed reaction of 1,1‐diphenylsilacyclobutanes with aryl halides gives ­unexpected products, triarylsilanols, after ­hydrolysis in moderate yields. The catalysis involves the reaction of aryl–palladium intermediates with silacyclobutanes along with ­regioselective aryl–silicon bond formation. Copyright © 2001 John Wiley & Sons, Ltd.
Synthesis of Si–C–N coatings by thermal Plasmajet chemical vapour deposition applying liquid precursors
Authors: Wilden Johannes , Wank Andreas , Asmann Marcus , Heberlein Joachim V. R. , Boulos Maher I. , Gitzhofer Francois
Published: August 2002

Materials in the system Si–C–N feature excellent properties for wear protection applications, even at elevated temperatures, and an excellent thermal shock resistance. As these materials have no melting point, coatings have to be manufactured via a synthesis. Conventional chemical vapour deposition (CVD) processes have the disadvantage of low deposition rates. Thermal Plasmajet CVD processes with liquid feedstock feature the highest deposition rates among the gas‐phase synthesis processes. Single and triple DC torches and HF torches with supersonic nozzles have successfully been applied to produce Si–C(–N) coatings on different steel, aluminium, titanium and copper alloys, as well as on graphite. Besides chlorosilanes, hexamethyldisiloxane, tetramethyldisiloxane and hexamethyldisilazane have been used as liquid single precursors. Deposition rates up to 1500 μm h−1 have been achieved. The coatings show cauliflower, columnar or dense morphology and an amorphous or nanocrystalline structure. The formation of both α‐ and β‐Si3N4 has been verified by X‐ray diffraction. The application of chlorosilanes always results in chlorine‐containing coatings. The chlorine causes severe corrosion in the interface to mild carbon steel substrates. The processes are compared taking into account their characteristics concerning the injection modes, gas temperature and velocity profiles determined by enthalpy probe measurements. The process conditions are correlated to the coating microstructure and the adhesion to the substrates and guidelines for the optimum production of ­Si–C–N coatings by Plasmajet CVD are deduced. Emission spectroscopy is used to determine the mechanisms of the coating formation. Full dissociation of the liquid feedstock in the plasma jet has been verified. Copyright © 2001 John Wiley & Sons, Ltd.
Poly‐DL‐lactide–poly(ethylene glycol) microspheres as oral and parenteral delivery systems for hepatitis B surface antigen
Authors: Li Xiaohong , Zhou Shaobing , Wu Xiaorong , Yuan Minglong , Liu Li , Jia Wenxiang , Deng Xianmo , Huang Zhitang
Published: August 2002

This project was aimed at illustrating the potential use of poly‐DL‐lactide–poly(ethylene glycol) (PELA) microspheres as a hepatitis B surface antigen (HBsAg) delivery system following subcutaneous (s.c.) or oral immunization over the current injection of an alum‐absorbed antigen. The antigen‐loading microspheres were elaborated by the solvent‐extraction method based on the formation of modified multiple w/o/w emulsion. The microspheres were characterized by their particle size, HBsAg entrapment, and in vitro HBsAg release behavior. Balb/c mice were immunized with an s.c. injection and oral administration of a single dose and two doses of a microsphere formulation. For comparison, the alum‐absorbed HBsAg‐immunized mice had a following intramuscular (i.m.) injection at weeks 0 and 4. At weeks 8, 10, 14, and 24 postadministration, the blood and saliva samples were collected and detected by the enzyme‐linked immunosorbed assay (ELISA) method. A single injection of HBsAg/PELA microspheres could induce a serum lgG antibody level comparable to the two‐injection alum‐absorbed HBsAg at the 14th week and higher than that at the 24th week. The saliva lgA of peroral groups was significantly higher than that of the s.c. injection of a microsphere formulation and i.m. injection of soluble antigen. These preliminary results demonstrated the potential of oral administration of antigen‐loading microspheres in the induction of a secretory immune response, and it is suggested that a single‐dose s.c. injection of antigen‐loading microspheres would be an efficient immunization schedule to elicit a protective response. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 83: 850–856, 2002
Rheological study of eucalyptus tar pitches
Authors: Prauchner Marcos J. , Pasa Vânya M. D. , Otani Choyu , Otani Satika
Published: August 2002

The development of advanced carbonaceous materials (ACMs) from biopitches is important to increase the revenue of the charcoal making industry and to stimulate the use of biomass, thereby attending to the appeals for environmental preservation. A pioneer study on the rheological behavior of eucalyptus tar pitches was carried out in this work. This behavior plays an important part in obtaining ACMs from pitch, particularly in the spinning step of carbon fiber production. Our results showed that biopitches have a strong dependence on the viscosity and temperature/softening point ratio. An Arrhenius‐type law gave the activation energies for viscous flow. Different from conventional polymers, this energy was higher for more polymerized pitches because of their higher molecular stiffness. The results obtained by the Williams–Landel–Ferry equation showed that the viscosity can be associated with the free volume. Lower viscosities correspond to larger free volume. The plot of the apparent viscosity versus the shear time at constant temperature and shear rate showed that the pitches have a purely viscous flow. Experiments that changed the shear rate showed that biopitches behave as Newtonian fluids. Purely viscous and Newtonian behaviors are desirable for more stable spinning. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 84: 900–908, 2002; DOI 10.1002/app.10096
Melt/solution processable conducting polyaniline: Elastomeric blends with EVA
Authors: Paul Raji K. , Pillai C. K. S.
Published: August 2002

Polyaniline (PANI) protonated with dopant, the sulfonic acid of 3‐pentadecylphenoxyacetic acid (SPDPAA; synthesized from an inexpensive naturally existing biomonomer, cardanol), was blended with an elastomeric polymer, the ethylene vinyl acetate (EVA) copolymer. Blending was performed either by emulsion polymerization of aniline into the EVA matrix or by the solution‐mixing method. Thin films were prepared by the conventional melt‐processing technique for an emulsion‐polymerized system and by the solution‐casting method for a solution‐mixed system. In the case of the emulsion‐polymerized system, the percolation threshold occurs at a very low weight percentage of PANI, and a maximum conductivity value of 0.85 S cm−1 was obtained for 28.5 wt % of PANI. These elastomeric conducting blends were characterized by elemental analysis, FTIR and UV‐visible spectral analysis, conductivity measurements, SEM, XRD, tensile properties, TGA, and DSC. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 84: 1438–1447, 2002; DOI 10.1002/app.10408