bluuebunny/crossref_metadata_2025 huggingface dataset:
Worldwide Use of the Ketogenic Diet
Authors: Kossoff Eric H. , McGrogan Jane R.
Published: January 2005

Summary:  Purpose: Over the past decade, the use of the ketogenic diet internationally has increased dramatically. The purpose of this survey was to evaluate the use of the diet worldwide.

Methods: With the use of the Internet, e‐mail requests for information about international ketogenic diet centers (outside the United States) were made over a 9‐month period. Assistance also was obtained from the Child Neurology Society and International League Against Epilepsy. Questions included patient enrollment (total and annually), year the diet was first offered, unique cultural and religious issues in the country, community opinion, and research interests.

Results: Successful communication was made with 73 academic centers in 41 countries outside the United States. Sixteen (39%) countries provided information from multiple centers. The median duration offering the diet was 8 years (range, 1–45 years). The average number of patients enrolled to date was 71.6 per country, with 5.4 new patients annually. Common difficulties included avoiding rice intake, tolerating higher fat‐to‐protein and carbohydrate ratios (e.g., 4:1), finding specific nutritional labels on foods, and handling the growing interest from large populations with limited resources. Nevertheless, cultural and religious issues were generally not limiting; physician and patient acceptance of the diet as an option is high; and most meals were similar among countries. Centers often had great pride in their programs, and international collaborative groups are forming rapidly. A website is now available with updated center information at http://www.neuro.jhmi.edu/Epilepsy/Peds/ketoworldwide.htm

Conclusions: Despite occasional difficulties, the ketogenic diet is being used worldwide.
Limbic Self‐sustaining Status Epilepticus in Rats Is Not Associated with Hyperthermia
Authors: Schmitt Friedhelm C. , Matzen Julia , Buchheim Katharina , Meierkord Hartmut , Holtkamp Martin
Published: January 2005

Summary:  Purpose: To evaluate the impact of limbic status epilepticus on temperature.

Methods: The perforant path in freely moving rats was stimulated electrically for 120 min to induce self‐sustaining status epilepticus (SSSE). For 150 min after the end of stimulation, epidural temperature and electrographic and clinical seizure activity were assessed in animals with limbic and motor SSSE, as well as in animals without development of SE.

Results: Temperature in all animals with SSSE was elevated by 1.5 ± 0.8°C after the end of stimulation compared with baseline values (p < 0.01). In animals with pure limbic SE, temperature decreased continuously to baseline values over the 150‐min period of observation. In contrast, in animals with motor SSSE, temperature remained elevated during continuing epileptic activity and was still significantly higher 150 min after the end of stimulation compared with baseline (p < 0.01). In animals that did not develop SSSE, temperature was not changed after the end of electrical stimulation and in the 150 min thereafter compared with baseline values.

Conclusions: The results indicate that hyperthermia as seen in SE is the consequence of motor convulsions and not of epileptic activity itself, as seen in limbic SSSE.
Kindling Limits the Interictal Neuronal Temporal Response Properties in Cat Primary Auditory Cortex
Authors: Valentine Pamela A. , Teskey G. Campbell , Eggermont Jos J.
Published: January 2005

Summary:  Purpose: The present study examined the effect of electrical kindling on the interictal temporal response properties of single units recorded from primary auditory cortex (AI) of the adult cat.

Methods: Cats were permanently implanted with electrodes in AI, kindled twice daily for 40 sessions, and the contralateral AI was subsequently mapped. Kindling stimulation consisted of 1‐s trains of biphasic square‐wave pulses applied at a frequency of 60 Hz, 100 μA above the afterdischarge (AD) threshold. The EEG activity was recorded during each kindling session, and the behavioral manifestation was scored. Subsequent to kindling, multiple single‐unit responses were recorded under ketamine anesthesia in response to 1‐s‐long periodic click trains, with click rates between 2 and 64 Hz. Neuronal responses were characterized according to their ability to respond in time‐locked fashion to the clicks.

Results: Kindling stimulation resulted in progression of the AD characteristics and seizure behavior, with six of 10 kindled cats reaching a fully generalized state. In the fully kindled cats, the best modulation frequencies and limiting following rates for the single‐unit responses were significantly lower compared with those of naive and sham controls.

Conclusions: Repeated epileptiform activity interferes with temporal processing in cat auditory cortex in the interictal state. This may have implications for people with epileptic foci in auditory‐related areas.
Efficacy and Safety of the Ketogenic Diet for Intractable Childhood Epilepsy: Korean Multicentric Experience
Authors: Chul Kang Hoon , Joo Kim Yong , Wook Kim Dong , Dong Kim Heung
Published: January 2005

Summary:  Purpose: We wished to evaluate the efficacy and safety of the ketogenic diet (KD), and we also evaluated the prognosis of the patients after successful discontinuation of the diet in infants, children, and adolescents with refractory epilepsy.

Methods: This was a retrospective study of epilepsy patients treated with the KD during 1995 through 2003 at the Korean multicenters. Outcome measures included seizure frequency, electroencephalography (EEG), adverse reactions, and antiepileptic drug (AED) number. The variables related to the efficacy and prognosis also were analyzed.

Results: The outcomes of the 199 patients enrolled in this study at 6 and 12 months after the diet were revealed; 68% and 46% of patients remained on the diet, 58% and 41% showed a reduction of seizure frequency of >50%, including 33% and 25% who became seizure free, respectively. Finally, 66 (34%) of 199 patients successfully completed or maintained the diet. EEGs showed an improvement in background in 40 (72.7%) of 55 patients and a reduction in generalized and focal discharges in 41 (57.7%) of 71 and 15 (33.3%) of 45 patients. Most complications were mild, but five patients died during the KD. No significant variables were related to the efficacy, but those with symptomatic (p = 0.047) and partial epilepsies (p = 0.073) showed more frequent relapse after completion of the diet.

Conclusions: The KD is a safe and effective alternative therapy for intractable childhood epilepsy in Korea, although the customary diet contains substantially less fat than traditional Western diets, but life‐threatening complications should be monitored closely during follow‐up.
Effect of sampling interval and temperature on the accuracy of food consumption estimates from stomach contents
Authors: Finstad A. G.
Published: January 2005

The effect of temperature and sampling interval on the accuracy of food consumption estimates based on stomach contents was studied using simulation. Three temporal patterns of feeding were considered (scattered throughout the day, one 5 h period or two 5 h periods) and gastric evacuation was modelled according to published values. Sampling intervals of 3 h gave reasonable food consumption estimates (2 to 19% error) at all temperatures. Comparably, sampling intervals as large as 12 h gave reasonable estimates of food consumption (1 to 20% error) when temperature was set to ≤10° C. At temperatures <5° C, even 24 h intervals (equivalent to one daily sampling) provided reasonable estimates of daily food consumption (2 to 19% error) for all but the highest gastric evacuation rate combined with one daily feeding period (47% error). The temperature effect on estimation error resulted from diminishing temporal fluctuations in stomach contents with slower gastric evacuation rates. It follows that sampling effort may be considerably minimized when estimating food consumption from stomach contents during periods with low temperatures such as the winter time experienced by temperate fishes.
Spawning characteristics of the anadromous brown trout in a small Swedish stream
Authors: Rubin J.‐F. , Glimsäter C. , Jarvi T.
Published: January 2005

The spawning pattern of the anadromous brown troutSalmo truttawas studied in Själsöån, a small stream in Gotland, Sweden, during eight winters between 1992–1993 and 1999–2000. The total length (LT) at spawning was normally distributed (185–890 mm) for females and multimodal for males (300, 400 and 550 mm most frequent length classes). Spawning males were significantly younger (2+ to 4+ years) than females (3+ to 5+ years). The sex‐ratio at the beginning and at the end of the spawning season favoured males. The mean ± s.d. number of spawners was 70 ± 16 individuals per year. Migration into and out of the stream occurred between November and June. The highest number of spawning fish was found in the stream at the end of November or at the beginning of December. Migration mainly occurred during high water flow and at night. The majority of the females entered the stream and spawned the same (29·3% of all the females) or the next night (32·8% of all the females) while males may have stayed for 2 to 3 weeks (21·3% of all the males) in the stream before spawning. Males usually remained much longer in the stream (mean ± s.d. 45 ± 56 days) than females (16 ± 30 days). Females lost more mass in the stream (mean ± s.d. 17·3 ± 8·6%) than males (7·7 ± 9·6%). For both sexes, mass loss was positively correlated with the time spent in the stream. Only 7·3% of the males and 5·7% of the females occurred in the stream for >1 year. Spawning took place only during the night.
The feeding behaviour of juvenile Atlantic salmon in relation to turbulent flow
Authors: Enders E. C. , Buffin‐Bélanger T. , Boisclair D. , Roy A. G.
Published: January 2005

The feeding behaviour of juvenile Atlantic salmon Salmo salar in the Sainte‐Marguerite River, Quebec, Canada, varied with the characteristics of turbulent flow. Simulations indicated that juveniles would decrease their swimming costs during attacks by 19·8% in low and by 31·1% in high turbulent conditions by initiating movements in low‐speed flow events. The real swimming costs did not differ from the swimming costs estimated for a situation where fish initiate their movements at randomly selected flow velocities. The juvenile Atlantic salmon did not seem to prefer low‐speed flow events when initiating their movements. The proportion of time used for movements by fish decreased with an increase in the mean and the s.d. of the flow velocity.
Assessing the Need for Child‐Care Health Consultants
Authors: Gaines Sherry K. , Wold Judith L. , Spencer Lorine , Leary Janie M.
Published: January 2005

Abstract  This study surveyed health and safety needs of child‐care programs; examined the perceptions of directors, the person identified as being responsible for a program, concerning health consultation; and determined how directors would secure funds to pay for consultative services. The survey was conducted in a state without mandates for child‐care health consultation and minimal access to consultants. The researchers designed and pilot‐tested a Child Care Health and Safety Survey. Working with a task group of statewide child health experts, the researchers revised the survey and mailed it to a random sample of child‐care programs. Twenty‐two Head Start Programs, 122 licensed child‐care centers, and 116 family child‐care homes participated, representing a return rate of 73, 36, and 30%, respectively. The majority of programs expressed interest in child‐care health consultation offered for free or fee‐based. Directors identified reasonable means of obtaining funds to support consultation. All programs had needs related to supporting health practices in their settings, provision of health services for staff, and health screening for children. Public health nurses, specially trained to advise child care, are well positioned to offer consultation. Systems of health consultation may be accepted as fee‐for‐service arrangements, supporting sustainability.
Teenage Contraceptive Use in Iceland: A Gender Perspective
Authors: Bender Sóley S. , Kosunen Elise
Published: January 2005

Abstract  Different gender beliefs toward contraception may affect contraceptive use among teenagers and need to be explored for the development of sexuality education and services aimed at this age group. A cross‐sectional national survey was conducted. A random sample of 1,405 sexually active teenagers, 1,181 girls, and 224 boys was studied. One quarter of the girls and one fifth of the boys had often/always used unsafe methods (withdrawal and natural methods), and about one third of the teenagers used contraceptive methods sporadically or not at all. Generally, teenage girls had more positive beliefs toward use of contraceptives, more positive friends, and more supportive parents regarding contraception than boys. Both genders were more likely to use contraceptives if they recognized the seriousness of pregnancy and easiness of making contraceptive plans. Additionally, teenage girls were more likely to use contraceptives if they were older at the time of sexual debut, were in a steady sexual relationship, considered contraceptive services good, believed in not taking chances, and their parents knew about their contraceptive use. Preventive strategies must primarily target those teenagers who start sexual debut early, are not in a steady relationship, and are not receiving parental support.
Risk Factors for an Untoward Medication Event Among Elders in Community‐Based Nursing Caseloads in Australia
Authors: Johnson Maree , Griffiths Rhonda , Piper Margaret , Langdon Rachel
Published: January 2005

Abstract  This study sought to develop and test a set of criteria to distinguish elders at high risk of an untoward medication event within community nursing caseloads. A descriptive correlational design was used to identify relevant risk factors for elders. Data on medication knowledge, regime, management abilities, and adherence were obtained from 111 elders receiving community nursing care. Four predictors—12 or more doses of medications per day, more than one prescriber, caregiver available, and sometimes forgetting to take medications—of complexity (R2 explaining 39% of the variance) and adherence (R2 explaining 49% of the variance) were identified as potential factors that subsequently confirmed a discrete group of high risk elders. The use of these four risk factors or screening criteria is recommended for older people within community nursing caseloads.
Doula Birth Support for Incarcerated Pregnant Women
Authors: Schroeder Carole , Bell Janice
Published: January 2005

Abstract  The objective of this study was to provide trained labor support (doulas) to pregnant women in jail. A multiagency intervention project provided doula birth services to pregnant women in urban jails. Program evaluation included interviews with women and written satisfaction surveys of providers and correctional officers. A convenience sample of 18 incarcerated women received doula services. A doula visited each woman in jail antepartum to review expectations for labor and birth; during hospitalization, the doula provided continuous support throughout labor and birth. Doulas visited women postpartum to review birth events. Surveys administered to providers and officers demonstrated high satisfaction with the program. Qualitative interviews with 14 women indicated unanimous support for the services and documented women's major concerns. Findings support offering doula services to all pregnant women in custody and expanding doula services to include early and comprehensive intervention coordinated by nurses.
Public Health Nurse Interventions for Women in a Dependency Drug Court
Authors: Somervell Ann M. , Saylor Coleen , Mao Chia‐Ling
Published: January 2005

Abstract  There is an increasing number of children placed in foster care due to abuse and neglect. Parents of these children often have difficult drug abuse problems leading to the removal of their children. The cost of caring for these children is staggering, reaching an estimated $24 billion. One program in Northern California that has been created to assist parents is dependency drug court. This research utilized qualitative and quantitative data to identify the perceived needs of women who have graduated from this dependency drug court (n = 50) and what they think the public health nurse (PHN) could do to intervene in the difficult process of going through dependency drug court and reunifying with their children. Two main themes emerged from select interviews with former drug court recipients who were functioning as “mentor moms” (n = 4). Common barriers contributed to stress during recovery, and specific strategies promoted reunification and program success. Among strategies recommended by the mentor moms was a suggestion for PHNs to bridge the information gap through regular reports on the development and health of their children during the time they reside in foster care.
Practical Suggestions for Community Interventions Using Participatory Action Research
Authors: Kelly Patricia J.
Published: January 2005

Abstract  Advanced practice nurses and nurse researchers with experience in clinical settings may encounter challenges in the initial development and implementation of community‐based projects. Participatory action research methodology, a user‐friendly framework for community‐based research activities, provides a way for researchers and community members to work together to define a problem, take action, and evaluate their work. This article attempts to bridge the theory‐implementation gap by describing background steps that researchers can use when conceptualizing and initiating a research project with community partners. Suggestions for initial steps and the planning and review cycles are presented, along with examples from the literature.
Short‐Term Effects of a Health Promotion Course for Taiwanese Nursing Students
Authors: Hsiao Ya‐Chu , Chen Mei‐Yen , Gau Yueh‐Mei , Hung Li‐Ling , Chang Shu‐Hung , Tsai Hsia‐Min
Published: January 2005

Abstract  The purposes of this study were to (a) develop a teaching course on health promotion for nursing students in Taiwan, (b) evaluate the effects of this teaching course, and (c) understand students’ appraisals of its effectiveness in helping them to change unhealthy behavior. A sample of 65 randomly selected female nursing students took an 18‐week course developed by the investigators, which included 30 h of classroom lectures and 4 weeks of written reports by students chronicling the changes in their behavior. Health promotion questionnaires administered before and after the course and content analysis of the students’ reports were used to evaluate the effects of the course. Students’ questionnaire scores after course completion indicated significantly increased intent to adopt healthy lifestyles. Content analysis of students’ reports on their personal behavior‐changing experiences showed that they accepted the potential value of curriculum aspects such as “experiencing the struggle, suffering, and even abandonment of the process,”“experiencing the benefits of change,”“increasing self‐confidence,” and “empathizing with how difficult it is for clients to change behavior.” These results support the value of teaching courses on health promotion to nursing students. The authors recommend including such a course as part of a regular nursing education.
Introgression of chukar genes into a reintroduced red‐legged partridge (Alectoris rufa) population in central Italy
Authors: Baratti M. , Ammannati M. , Magnelli C. , Dessì‐Fulgheri F.
Published: January 2005

Insight regarding the genetic origin and composition of the studied population of the red‐legged partridge (Alectoris rufa) is likely to provide general and critical information for the appropriate management and possible conservation of the species. The reintroduced population of red‐legged partridges living in Pianosa Island (National Park Tuscany Archipelago) has proven to be sustainable: captive‐bred individuals, morphologically assigned to the taxon A. rufa, were released to the island approximately 20 years ago, establishing an apparently well‐adapted population. We have investigated this population by means of 10 microsatellite loci in order to shed light on its genetic structure. Considering that A. rufa is known to crossbreed with A. chukar, the Pianosa Island population was compared at the molecular level with a red‐legged partridge breeding stock (Aulla, MS) as well as with a population of pure A. chukar. Our results indicate that the red‐legged partridge population from Pianosa, morphologically identified as A. rufa, is actually partly introgressed with A. chukar, questioning its genetic purity and the possible use of this population as a starting stock for future reintroductions elsewhere.
Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia
Authors: Elliott M. A. , Tefferi A.
Published: January 2005

Despite decades of clinical and laboratory research, relatively little has been accomplished concerning the pathogenesis as well as the identification of risk factors for thrombosis and bleeding in myeloproliferative disorders. In polycythaemia vera, the pro‐thrombotic effect of an elevated haematocrit is well established. In contrast, thrombocytosis per se has not been similarly incriminated in essential thrombocythaemia. In both conditions, advanced age and the presence of a prior event identify thrombosis‐prone patients. There is increasing evidence to suggest an additional role by leucocytes that might partly explain the antithrombotic effects of myelosuppressive therapy. A substantial minority of affected patients display reduced levels of high molecular weight von Willebrand protein in the plasma during extreme thrombocytosis and it is believed that this might explain the bleeding diathesis of such patients. Recent controlled studies support the therapeutic value of hydroxyurea and aspirin in essential thrombocythaemia and polycythaemia vera, respectively. The current communication will address the incidence, phenotype, pathogenesis, risk factors, prevention, and treatment of both thrombosis and haemorrhage in these disorders.
The crucial role of vascular permeability factor/vascular endothelial growth factor in angiogenesis: a historical review
Authors: Ribatti Domenico
Published: January 2005

Angiogenesis is a biological process by which new capillaries are formed and it occurs in many physiological and pathological conditions. It is controlled by the net balance between molecules that have positive and negative regulatory activity and this concept had led to the notion of the ‘angiogenic switch’, depending on an increased production of one or more of the positive regulators of angiogenesis. Numerous inducers of angiogenesis have been identified and this review offers a historical account of the relevant literature concerning the discovery of one of the best characterized angiogenic factors, namely vascular endothelial growth factor (VEGF)/vascular permeability factor. Moreover, different strategies, designed to stimulate and to inhibit VEGF production in the context of several potential therapeutical implications, are discussed.
Management of thrombosis in cancer: primary prevention and secondary prophylaxis
Authors: Lee Agnes Y. Y.
Published: January 2005

Although traditional anticoagulant regimens are highly effective and safe in most patients with venous thromboembolism (VTE), the aggressive natural history of VTE and the high risk of serious bleeding in cancer patients can complicate the management of VTE. In addition, because few clinical trials have focused on the prevention and treatment of VTE in this unique patient population, many clinical questions regarding the care of cancer patients with VTE remain unanswered. Currently, low‐molecular‐weight heparins and oral vitamin K antagonists are the most commonly used agents for the primary and secondary prophylaxis of VTE in patients with or without cancer, but their use is associated with pharmacological and practical limitations. This review will provide an up‐to‐date summary of the clinical trials that have addressed the management of VTE in patients with cancer. A brief discussion of the potential application of novel anticoagulants in these clinical settings is also included.
Severe FVII deficiency caused by a new point mutation combined with a previously undetected gene deletion
Authors: Hewitt Jeff , Ballard Jennifer N. M. , Nelson Tanya N. , Smith Valerie C. , Griffiths Tanya A. M. , Pritchard Sheila , Wu John K. , Wadsworth Louis D. , Casey Brett , MacGillivray Ross T. A.
Published: January 2005

A 3‐week‐old Caucasian female presented with severe unprovoked parenchymal cerebral haemorrhage. Her plasma factor VII (FVII) activity was <0·01 units/ml. FVII activities for her mother and sister were 0·65 units/ml and 0·51 units/ml, respectively, while her father's level was normal. These results indicated that the mother was heterozygous for a non‐functional F7 gene that had also been inherited by the proband's sister. The proband's severe FVII deficiency was caused by a new mutation in her paternal F7 gene coupled with the inheritance of the non‐functional maternal F7 gene. DNA sequence analysis revealed that the proband had apparent homozygosity for a novel single point mutation (g.3907G > A) changing the codon for Glu29 to Lys (E29K); neither parent had the E29K mutation. Because of the unlikelihood that the proband was homozygous for two identical new point mutations, the DNA sequence abnormality was more likely to have arisen from a single mutated gene on one allele and a F7 gene deletion on the other allele. Real time polymerase chain reaction (PCR) analysis confirmed that the proband had inherited a gene deletion that was present in the maternal side of the family. Subsequent clotting assays and real time PCR revealed that the maternal deletion also included the closely linked F10 gene.
Inactivation of parvovirus B19 by liquid heating incorporated in the manufacturing process of human intravenous immunoglobulin preparations
Authors: Yunoki Mikihiro , Urayama Takeru , Tsujikawa Muneo , Sasaki Yoshie , Abe Shunichi , Takechi Kazuo , Ikuta Kazuyoshi
Published: January 2005

Several reports have suggested the possible transmission of human parvovirus B19 (B19) through the administration of plasma derivatives that had undergone virus inactivation by various types of heat treatment. However, none of the reports evaluated and discussed the inactivation of B19 by the heat treatment that is implemented in the individual manufacturing processes of such products. The present study evaluated the ability to inactivate B19 of liquid‐heat treatment at 60°C for 10 h that was incorporated in the manufacturing process of intravenous human immunoglobulin preparations. The results showed that B19 was rapidly inactivated under the conditions used for the liquid‐heat treatment.
Pre‐transfusion management of children with severe malarial anaemia: a randomised controlled trial of intravascular volume expansion
Authors: Maitland Kathryn , Pamba Allan , English Michael , Peshu N. , Levin Michael , Marsh K. , Newton Charles R.J.C.
Published: January 2005

Symptomatic severe malarial anaemia (SMA) has a high fatality rate of 30–40%; most deaths occur in children awaiting blood transfusion. Blood transfusion services in most of Africa are not capable of delivering adequate supplies of safe blood in a timely manner to critically ill children with SMA. Contrary to widely held belief, hypovolaemia, rather than heart failure, has emerged as a common complication in such children. We examined the safety of pre‐transfusion management (PTM) by volume expansion, aimed at stabilizing children and obviating the urgency for blood transfusion. Kenyan children with severe falciparum anaemia (haemoglobin < 5 g/dl) and respiratory distress were randomly assigned to 20 ml/kg of 4·5% albumin or 0·9% saline or maintenance only (control) while awaiting blood transfusion. PTM was apparently safe since it did not lead to the development of pulmonary oedema or other adverse events. There was no significant difference in the primary outcome [mean percentage reduction in base excess between admission and 8 h (95% confidence interval)] between the control group 42% (19–66%) albumin group 44% (32–57%) and saline group 36% (16–57%); adjusted analysis of variance F = 0·31, P = 0·7. However, the number of children requiring emergency interventions was significantly greater in the control group, four of 18 (22%) than the saline group 0 of 20 (P = 0·03). We have established the safety of this PTM in children with SMA whilst awaiting blood transfusion at a hospital with an adequate blood‐banking program. The impact on mortality should be assessed where blood transfusion services are unable to supply emergency transfusions.
The NFATc1 transcription factor is widely expressed in white cells and translocates from the cytoplasm to the nucleus in a subset of human lymphomas
Authors: Marafiot Teresa , Pozzobon Michela , Hansmann Martin‐Leo , Ventura Roland , Pileri Stefano A. , Roberton Helen , Gesk Stefan , Gaulard Philippe , Barth Thomas F. E. , Du Ming Q. , Leoncini Lorenzo , Möller Peter , Natkunam Yasodha , Siebert Reiner , Mason David Y.
Published: January 2005

Stimulation of lymphoid cells via their surface receptors triggers signalling pathways that terminate in the nucleus, where they induce alterations in gene transcription. Nuclear factor of activated T cells (NFAT) transcription factors, involved in a major Ca2+‐dependent signalling pathway, normally reside in the cytoplasm but re‐locate to the nucleus when activation of the pathway (e.g. following ligation of antigen receptors) leads to their dephosphorylation. This study found that one member of the NFAT family (NFATc1/NFAT2) can be detected in routine biopsy samples, where it is seen in essentially all lymphoid cells, but is absent from the great majority of non‐haematopoietic cells. An immunohistological evaluation of NFATc1 in almost 300 lymphomas showed that most neoplastic lymphoid cells also express NFATc1 as a cytoplasmic constituent, although it is absent in classical Hodgkin's disease and plasma cell proliferations. Of particular interest was the finding that NFATc1 was relocated to the nucleus in a minority of lymphoid neoplasms (usually diffuse large B‐cell lymphomas or Burkitt lymphoma), presumably reflecting activation of the NFAT pathway. It would be of interest to correlate this feature with patterns of gene expression and also with prognosis, since it may identify a subset of human lymphoma that is distinct in its molecular and clinical features.
Antiphospholipid antibodies in immune thrombocytopenic purpura tend to emerge in exacerbation and decline in remission
Authors: Bidot Carlos J. , Jy Wenche , Horstman Lawrence L. , Ahn Eugene R. , Jimenez Joaquin J. , Yaniz Miriam , Lander Gabriela , Ahn Yeon S.
Published: January 2005

Although the presence of antiphospholipid antibodies (APLA) in immune thrombocytopenic purpura (ITP) has been reported, their clinical significance is not clear. The present study investigated APLA profiles in relation to the clinical stages of ITP. We studied APLA in 40 patients in three stages of ITP: exacerbation/relapse (n = 7), stable (n = 14) and remission (n = 19). Both IgG and IgM APLA to six target antigens were measured by enzyme‐linked immunosorbent assay: β2‐glycoprotein 1 (β2GP1), cardiolipin, phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine and factor VII/VIIa. The central finding was that APLA were common in ITP but differed significantly in disease stages, being highest in exacerbation (86% positive), intermediate in stable disease (57%) and lowest in remission (42%). In exacerbations, APLA were predominantly of IgG class, while in stable disease, IgM predominated. During remission, APLA often became undetectable. Both the frequency and titres of APLA were significantly higher during exacerbation than remission. An inverse correlation was found between platelet count and nearly all APLA (except β2GP1). Sequential study of six patients revealed that APLA tended to emerge and rise with exacerbation, concurrently with new episodes of bleeding and became undetectable during remission. These findings raise the possibility that APLA may play a role in the exacerbation and remission of ITP or they may be a consequence of platelet destruction.
Tolerance to intravenous heparin in patients with delayed‐type hypersensitivity to heparins: a prospective study
Authors: Gaigl Zeno , Pfeuffer Petra , Raith Petra , Bröcker Eva‐B. , Trautmann Axel
Published: January 2005

Delayed‐type hypersensitivity to subcutaneously injected heparin is relatively common. Particularly, extensive cross‐reactivity between different heparins and heparinoids often occurs. Delayed‐type hypersensitivity to heparin implies the risk of a generalized eczema when heparin is administered intravenously. However, case reports demonstrated a tolerance to intravenous heparin in patients with delayed‐type hypersensitivity to subcutaneous heparin, but prospective studies have not been performed. Our study group, of 28 patients with a proven delayed‐type hypersensitivity to subcutaneous heparin, was challenged with intravenous heparin, which was well tolerated in all 28 patients. Therefore, in case of therapeutic necessity, the shift from subcutaneous to intravenous heparin administration is justified.
Gemtuzumab ozogamicin (Mylotarg) has therapeutic activity against CD33+ acute lymphoblastic leukaemias in vitro and in vivo
Authors: Golay J. , Di Gaetano N. , Amico D. , Cittera E. , Barbui A. M. , Giavazzi R. , Biondi A. , Rambaldi A. , Introna M.
Published: January 2005

Gemtuzumab ozogamicin (GO) is a humanized anti‐CD33 antibody conjugated with the cytotoxic drug calicheamicin and approved for the treatment of relapsed acute myeloid leukaemia. As approximately 18% of acute lymphoblastic leukaemias (ALL) are also CD33 positive, we have investigated the cytotoxic activity of GO on CD33+ ALL cells in vitro and in vivo. 10 ng/ml GO induced 30–95% inhibition of thymidine uptake and 30–70% cell death in four freshly isolated and one in vivo passaged CD33+ ALL‐cell cultures. Furthermore, an in vivo model of a CD33+ ALL carrying the Philadelphia chromosome [t(9;22)] was established. 5 × 106 ALL‐2 cells inoculated in the tail vein of severe combined immunodeficient mice engrafted into haematopoietic organs, reaching a mean of 70%, 61% and 69% human CD45+ cells in bone marrow, spleen and liver, respectively, at 35 d. To test the therapeutic activity of GO, 50 or 100 μg immunotoxin was inoculated i.p. on days 7, 11 and 15 following tumour‐cell inoculation. GO treatment dramatically inhibited expansion of ALL‐2 cells in all tested organs and increased survival of tumour‐injected animals by 28–41 d, relative to controls. These data demonstrated that GO is active both in vitro and in vivo against CD33+ ALL cells.
First description of somatic mosaicism in MYH9 disorders
Authors: Kunishima Shinji , Matsushita Tadashi , Yoshihara Takao , Nakase Yoko , Yokoi Kentaro , Hamaguchi Motohiro , Saito Hidehiko
Published: January 2005

MYH9 disorders are characterized by giant platelets, thrombocytopenia, and Döhle body‐like cytoplasmic granulocyte inclusion bodies that result from mutations in MYH9, which encodes non‐muscle myosin heavy chain‐A (NMMHCA). These disorders are known to be transmitted in an autosomal dominant manner, although about 20% of cases are considered to be sporadic. We report here the first case of a MYH9 disorder because of somatic mosaicism. The patient was the father of a male with typical May–Hegglin anomaly. The father had normal platelet counts, however, both normal‐sized and giant platelets were observed on his peripheral blood smears. In addition, 14% of neutrophils contained inclusion bodies and the rest showed a normal morphology. Quantitative fluorescent polymerase chain reaction analysis showed that only 6% of DNA from peripheral blood leucocytes harboured the mutation. The mosaicism was demonstrated at a similar rate in different tissues, buccal mucosa cells and hair bulb cells, implying that the mutation had occurred before gastrulation. Mosaicism might account for some de novo mutations in MYH9 disorders.
Thrombotic thrombocytopenic purpura in patients with retroviral infection is highly responsive to plasma infusion therapy
Authors: Novitzky Nicolas , Thomson Jacqueline , Abrahams Louise , Du Toit Cécile , McDonald Andrew
Published: January 2005

We prospectively studied presentation biological differences and the response to therapy in patients with thrombotic thrombocytopenic purpura (TTP) associated with, or unrelated to human immunodeficiency virus (HIV) infection. TTP patients underwent standard evaluations and were treated with prednisone 1 mg/kg in addition to infusions of fresh frozen plasma (FFP; 30 ml/kg/d) until normalization of the platelet count. Unresponsive patients were referred for plasma exchange. Compared with HIV− TTP patients (n = 23), in HIV+ subjects (n = 21) microangiopathy was dominant among Black females, who had lower presentation Hb (median 5·8 g/dl; P = 0·03), platelet count (13 × 109/l; P = 0·05) and a CD4 count of 0·096 × 109/l. HIV+ individuals responded to FFP faster than HIV− patients and none of them required apheresis. Ten HIV− TTP patients required apheresis (P = 0·03) and four died. Responses in the HIV+ and HIV− groups occurred after treatment with a median of 33 and 55 units (one unit = 320 ml) of FFP (P = 0·004) respectively. Response to this protocol was seen in 84% (95% response in HIV+ patients). Regression analysis showed that survival was associated with younger age (P = 0·001), rapid platelet (P = 0·001) and Hb (P = 0·0009) recovery, and fewer FFP units to normal lactate dehydrogenase levels (P = 0·006). We conclude that in HIV+ individuals, microangiopathy is highly responsive to plasma infusions. This observation is important particularly when apheresis is not available.
Factor V Leiden, prothrombin 20210A and the risk of venous thrombosis among cancer patients
Authors: Kennedy Margaret , Andreescu Astrid C. M. , Greenblatt Marc S. , Jiang Hongyu , Thomas Christian A. , Chassereau Laurie , Wong Cheung , Durda Peter , Cushman Mary
Published: January 2005

Cancer patients have an increased risk of venous thrombosis (VT). The association of factor V Leiden (FVL) and the prothrombin 20210A variant with VT in cancer patients is not established. We genotyped 101 cancer patients with VT and 101 cancer patients without VT for these polymorphisms. Five cases and three controls were heterozygous for FVL, yielding an odds ratio of 1·7 (95% confidence interval (CI) 0·3–10·7). Five cases and no controls were heterozygous for prothrombin 20210A, for an odds ratio of 6·7 (95% CI 0·9–infinity). Prothrombin 20210A may be associated with VT risk among cancer patients.
Molecular events associated with accelerated proliferative response in rat livers when partial hepatectomy is preceded by a sham operation
Authors: Laurent S. , Stärkel P. , Leclercq I. A. , Lambotte L. , Maiter D. , Horsmans Y.
Published: January 2005

Background  When a sham operation is performed 6 h before partial hepatectomy (PH), the regenerative response is accelerated suggesting that sham operation itself contributes to cellular events leading to proliferation.

Materials and methods  In order to examine the mechanisms implicated in this acceleration, we compared the activation of several factors associated with the progression through the cell cycle at various times after PH and after PH preceded by sham operation (S6 h + PH). The effect of a single sham (S) and two combined sham operations (S6 h + S) was also examined. Nonoperated rats were used as controls (C).

Results  The early factors NF‐κB and Stat3 were activated after S6 h + PH and S6 h + S. C‐jun expression was increased 0·5 h and 2 h after PH and 6 h after sham. There was no further increase in S6 h + PH and S6 h + S. In contrast, c‐myc expression returned to baseline levels after S6 h and a new increase was observed 2 h after S6 h + PH but not after S6 h + S. P53 mRNA was significantly expressed 6 h after S6 h + PH, but at a level similar than that observed 6 and 12 h after PH alone. An earlier increase in c‐Ha‐ras mRNA and cyclin E protein was found in S6 h + PH, in comparison with PH alone.

Conclusions  The first divergent response between the two combined models involved c‐myc expression. However, major differences related to the accelerated liver regenerative response observed after S6 h + PH were found at late time points associating an earlier expression of c‐Ha‐ras and nuclear cyclin E.
Peroxisome proliferator‐activated receptor γ: the more the merrier?
Authors: Argmann C. A. , Cock T.‐A. , Auwerx J.
Published: January 2005

The consequence of activating the nuclear hormone receptor, peroxisome proliferator‐activated receptor gamma (PPARγ), which coordinates adipocyte differentiation, validates the concept, ‘you are what you eat’. Excessive caloric intake leads to fat formation if the energy from these nutrients is not expended. However, this evolutionary adaptation to store energy in fat, which can be released under the form of fatty acids, potent PPARγ agonists, has become a disadvantage in today's affluent society as it results in numerous metabolic imbalances, collectively known as the metabolic syndrome. With the surge of human and genetic studies on PPARγ function, the limitations to the benefits of PPARγ signalling have been realized. It is now evident that the most effective strategy for resetting the balance of this thrifty gene is through its modulation rather than full activation, with the goal to improve glucose homeostasis while preventing adipogenesis. Finally, as more PPARγ targeted pathways are revealed such as bone homeostasis, atherosclerosis and longevity, it is most certain that the PPARγ thrifty gene hypothesis will evolve to incorporate these.
Asymmetric dimethylarginine (ADMA): the silent transition from an ‘uraemic toxin’ to a global cardiovascular risk molecule
Authors: Fliser D.
Published: January 2005

Endothelial dysfunction as a result of reduced bioavailability of nitric oxide (NO) plays a central role in the process of atherosclerotic vascular disease. In endothelial cells NO is synthesized from the amino acidl‐arginine by the action of the NO synthase (NOS), which can be blocked by endogenous inhibitors such as asymmetric dimethylarginine (ADMA). Acute systemic administration of ADMA to healthy subjects significantly reduces NO generation, and causes an increase in systemic vascular resistance and blood pressure. Increased plasma ADMA levels as a result of reduced renal excretion have been associated with atherosclerotic complications in patients with terminal renal failure. However, a significant relationship between ADMA and traditional cardiovascular risk factors such as advanced age, high blood pressure and serum LDL‐cholesterol, has been documented even in individuals without manifest renal dysfunction. As a consequence, the metabolism of ADMA by the enzyme dimethylarginine dimethylaminohydrolase (DDAH) has come into the focus of cardiovascular research. It has been proposed that dysregulation of DDAH with consecutive increase in plasma ADMA concentration and chronic NOS inhibition is a common pathophysiological pathway in numerous clinical conditions. Thus, ADMA has emerged as a potential mediator of atherosclerotic complications in patients with coronary heart disease, peripheral vascular disease, stroke, etc., being the culprit and not only an innocent biochemical marker of the atherosclerotic disease process.
Is postprandial hypertriglyceridaemia in relatives of type 2 diabetic subjects a consequence of insulin resistance?
Authors: Kriketos A. , Milner K.‐L. , Denyer G. , Campbell L.
Published: January 2005

Background  Higher postprandial triglyceride responses reported in first degree relatives of people with type 2 diabetes (REL) were postulated to be the result of an early, possibly intrinsic, defect in oral lipid handling. The postprandial triglyceride response to high fat meals (HFM) in normal subjects is reduced by the insulin response to dietary carbohydrate (CHO) in the meal. The aims of this study were to examine whether (1) insulin resistance is associated with an intrinsic defect in triglyceride handling in insulin‐resistant REL and (2) insulin resistance is associated with altered triglyceride handling after HFM with high CHO content.

Materials and methods  Postprandial responses to a HFM in normolipidaemic, normoglycaemic REL were compared with subjects without a family history of diabetes mellitus (CON). Over 6 h, the insulin, glucose, triglyceride and nonesterified fatty acid (NEFA) responses after a high fat (80 g fat), low CHO (HFM‐LC; 20 g CHO, 4250 kJ) meal and a high fat, high CHO (HFM‐HC; 100 g CHO, 5450 kJ) meal were examined.

Results  The 10 (7F/3M) REL were significantly more insulin‐resistant, determined by glucose infusion during a hyperinsulinaemic euglycaemic clamp than the 10 (5F/5M) CON (glucose infusion rate 44·6 ± 4·9 vs. 60·0 ± 4·8 µmol min−1 kg FFM−1, P = 0·037). Subjects were similar for age and body mass index (BMI). The triglyceride increments after the HFM‐LC were similar in both, peaking at 180–240 min (Δ0·77 ± 0·11 mmol L−1), demonstrating no postprandial defect in REL, despite insulin resistance.

There was a significantly lower postprandial triglyceride response in CON following the HFM‐HC compared with the HFM‐LC, but not in REL. In contrast, the higher insulin level during the HFM‐HC was associated with significantly greater NEFA level suppression than in the HFM‐LC (2·13 ± 0·51 vs. 0·70 ± 0·35 mmol L−1, P = 0·03), only in the REL.

Conclusions  These results are inconsistent with a primary aetiological role for postprandial hypertriglyceridaemia in already insulin resistant type 2 diabetic REL, but raise the possibility that this potentially atherogenic manifestation is secondary to insulin resistance lessening VLDL production and/or release from the liver.
Autoantibodies against pituitary proteins in patients with adrenocorticotropin‐deficiency
Authors: Bensing S. , Kasperlik‐Zaluska A. A. , Czarnocka B. , Crock P. A. , Hulting AL.
Published: January 2005

Background  An autoimmune cause of adrenocorticotropin (ACTH)‐deficiency is presented, as it is known to be a characteristic feature of lymphocytic hypophysitis, a disease of the pituitary gland considered to be autoimmune.

Materials and methods  The aim of this study was twofold: (1) to evaluate the occurrence of pituitary autoantibodies and (2) to correlate it to clinical and immunological features in a large group of patients with ACTH‐deficiency of possible autoimmune aetiology. Sixty‐five patients with ACTH‐deficiency and 57 healthy subjects participated in the study. Pituitary autoantibodies were measured by an immunoblotting assay with human pituitary cytosol as antigen.

Results  Autoantibodies to a novel 36‐kDa pituitary autoantigen were seen in sera from 18·5% (12/65) patients and only 3·5% (2/57) of control subjects (P = 0·0214). When taking only those subjects with strong immunoreactivity into account, the significance was lost; P = 0·3642. Immunoreactivity to a 49‐kDa pituitary autoantigen was observed in 21·5% (14/65) of ACTH‐deficient patients compared with 8·8% (5/57) of control subjects (P = 0·0910). This 49‐kDa pituitary autoantigen has recently been identified as neurone‐specific enolase and a candidate marker for neuroendocrine autoimmunity. Clinical parameters in patients with positive versus those with negative pituitary immunoreactivity did not differ. However, autoantibodies to thyroglobulin were positively correlated to immunoreactivity against the 36‐kDa pituitary autoantigen (P = 0·014).

Conclusions  Our findings of pituitary autoantibodies in patients’ sera support the theory that an autoimmune destruction of corticotrophs may be the underlying cause of hormonal deficit in some patients with ACTH‐deficiency.