bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abnormal alterations in the metabolic patterns of patients on valproate therapy
Authors: Kreher U , Darius J , Wien F 
Published: October 2002

Abstract
Four cases of abnormal metabolic patterns which were obtained from three infantile patients and one adult on valproate (valproic acid; 2-n-propyl-pentanoic acid) therapy are reported. Serum levels of valproate and 15 metabolites were measured by gas chromatography/mass spectrometry. A mentally retarded, 11-month-old boy developed an extremely altered metabolic profile after having been treated with valproate polytherapy for 3 months. The altered pattern included strongly elevated serum levels of the 4-ene as well as of the x-/x 1-metabolites, with the b-metabolites (2-ene; 2,3′-diene) being diminished. Two samples obtained previously had shown a common pattern. The infant died 3 weeks after the last sample had been taken. Two boys of the same age showed similar but less intense deviations in their metabolic profiles at the onset of valproate therapy. Within a few weeks they approached, in a step-wise fashion, the average pattern common for children under 3 years of age. The striking alterations were paralleled by the metabolic profiles of an adult patient who suffered from intrahepatic metastasis and renal insufficiency. From the close resemblance of the abnormal metabolic patterns it was concluded that liver dysfunction results in alteration of the whole metabolic system. Regular inspection of the entire profile of an individual might help to recognize conspicuous alterations in time to avoid severe side effects.
Effects of classical antiepileptics on thresholds for phenomena induced by cortical stimulation in rats
Authors: Haugvicová R , Bílková E , Kubová H , Mareš P 
Published: October 2002

Abstract
Our aim was to study the effects of phenobarbital, phenytoin and ethosuximide on epileptic afterdischarges induced by cortical stimulation in rats. Fifteen-second series of low-frequency (8 Hz) rhythmic stimulation of the sensorimotor cortex were applied in rats with chronically implanted electrodes. Intervals between the stimulation series were at least 10 min and intensity was increased in a step-wise manner. Threshold current intensities were estimated for movements directly induced by stimulation, epileptic afterdischarges of the spike-and-wave type, clonic seizures accompanying this type of afterdischarge and transition into the limbic type of afterdischarge. Phenobarbital, phenytoin and ethosuximide were administered intraperitoneally before the first stimulation series. Phenobarbital (20, 40 and 80 mg kg−1) significantly increased the thresholds for the first three phenomena in a dose-dependent manner. Transition into the limbic afterdischarge was influenced only by the highest dose. Phenytoin (60 mg kg−1) only increased the thresholds insignificantly and ethosuximide (125 mg kg−1) was ineffective. We concluded that our model is useful for testing anticonvulsant effects. Results with three antiepileptic drugs correspond with their efficacy against myoclonic seizures in man.
Approximate entropy for testing randomness
Authors: Rukhin Andrew L. 
Published: October 2002

This paper arose from interest in assessing the quality of random number generators. The problem of testing randomness of a string of binary bits produced by such a generator gained importance with the wide use of public key cryptography and the need for secure encryption algorithms. All such algorithms are based on a generator of (pseudo) random numbers; the testing of such generators for randomness became crucial for the communications industry where digital signatures and key management are vital for information processing.The concept of approximate entropy has been introduced in a series of papers by S. Pincus and co-authors. The corresponding statistic is designed to measure the degree of randomness of observed sequences. It is based on incremental contrasts of empirical entropies based on the frequencies of different patterns in the sequence. Sequences with large approximate entropy must have substantial fluctuation or irregularity. Alternatively, small values of this characteristic imply strong regularity, or lack of randomness, in a sequence. Pincus and Kalman (1997) evaluated approximate entropies for binary and decimal expansions of e, π, √2 and √3 with the surprising conclusion that the expansion of √3 demonstrated much less irregularity than that of π. Tractable small sample distributions are hardly available, and testing randomness is based, as a rule, on fairly long strings. Therefore, to have rigorous statistical tests of randomness based on this approximate entropy statistic, one needs the limiting distribution of this characteristic under the randomness assumption. Until now this distribution remained unknown and was thought to be difficult to obtain. To derive the limiting distribution of approximate entropy we modify its definition. It is shown that the approximate entropy as well as its modified version converges in distribution to a χ2-random variable. The P-values of approximate entropy test statistics for binary expansions of e, π and √3 are plotted. Although some of these values for √3 digits are small, they do not provide enough statistical significance against the randomness hypothesis.
New improved bounds for reliability of consecutive-k-out-of-n:F systems
Authors: Muselli Marco 
Published: October 2002

New bounds are found for the reliability of consecutive-k-out-of-n:F systems with equal component failure probabilities. The expressions involved are simple, thus allowing a direct use in the derivation of theoretical properties.These bounds can also be employed in numerical computations when the value ofnorkis so large that the exact calculation of the reliability is not achievable. Comparisons show that the approximation errors exhibited by these new formulas are lower than those of other widely used bounds.
Amish lethal microcephaly: A new metabolic disorder with severe congenital microcephaly and 2‐ketoglutaric aciduria
Authors: Kelley Richard I. , Robinson Donna , Puffenberger Erik G. , Strauss Kevin A. , Morton D. Holmes 
Published: October 2002

AbstractA new metabolic disorder characterized by severe congenital microcephaly, death within the first year, and severe 2‐ketoglutaric aciduria has been found among the Old‐Order Amish of Lancaster County, Pennsylvania. Amish lethal microcephaly segregates as an autosomal recessive disorder and has an unusually high incidence of at least 1 in 500 births. When the infants are well, the urine organic acid profiles show isolated, extreme elevations of 2‐ketoglutaric acid. However, during otherwise simple viral illnesses, the infants often develop a metabolic acidosis, which may follow a lethal course. Cranial magnetic resonance imaging of a single patient showed a smooth, immature brain similar to that of a 20‐week fetus except for a moderate degree of cerebellar vermal hypoplasia. Assay of 2‐ketoglutarate dehydrogenase in cultured lymphoblasts of one patient showed normal activity. Amish lethal microcephaly maps to 17q25 and may be caused by a defect in a mitochondrial inner membrane protein functioning as a 2‐ketoglutarate transporter. © 2002 Wiley‐Liss, Inc.
Two cases of the caudal duplication anomaly including a discordant monozygotic twin
Authors: Kroes H.Y. , Takahashi M. , Zijlstra R.J. , Baert J.A.L.L. , Kooi K.A. , Hofstra R.M.W. , van Essen A.J. 
Published: October 2002

AbstractWe present two unrelated patients with various duplications in the caudal region. One patient presented with a duplication of the distal spine from L4, left double ureter, duplication of the vagina and cervix, and duplication of the distal colon. The second patient was diagnosed with a duplication of the colon, bladder, vagina and uterus. The first patient had an unaffected monozygotic twin sister. Dominguez et al. [1993: Am J Dis Child 147:1048–1052] presented six similar cases, and introduced the name “caudal duplication syndrome.” The pathogenesis of the caudal duplication anomaly is unclear. The possibility of a polytopic primary developmental field defect or a disruptive sequence are discussed. On the other hand, somatic or germline mutations in certain developmental genes could be involved, as illustrated by the mouse mutations disorganisation and fused. DNA‐analysis of the AXIN1 gene, the human homologue of the gene responsible for fused, performed in our first patient, did not show any apparent pathogenic mutation. © 2002 Wiley‐Liss, Inc.
Clinical and genetic heterogeneity of Seckel syndrome
Authors: Faivre L. , Le Merrer M. , Lyonnet S. , Plauchu H. , Dagoneau N. , Campos‐Xavier A.B. , Attia‐Sobol J. , Verloes A. , Munnich A. , Cormier‐Daire V. 
Published: October 2002

AbstractSeckel syndrome is a rare autosomal recessive condition belonging to the group of osteodysplastic primordial “dwarfism” and characterized by the association of 1) severe pre‐ and postnatal growth retardation, 2) microcephaly with mental retardation, and 3) specific dysmorphic features. Recently, two disease loci have been mapped to chromosomes 3q22.1‐q24 and 18p11.31‐q11.2, respectively, by homozygosity mapping in consanguineous families. Here, we report on the exclusion of these loci in five consanguineous and one multiplex nonconsanguineous Seckel syndrome families and in two consanguineous families presenting type II osteodysplastic primordial dwarfism. These results support the view that Seckel syndrome is a clinically and genetically heterogeneous condition. © 2002 Wiley‐Liss, Inc.
Tibial/femoral hypoplasia with “hook” pelvis: A potentially unique dysostosis
Authors: Mégarbané André , Ghanem Ismat 
Published: October 2002

AbstractWe report a 2‐year‐5‐month‐old girl with malformed lower limbs. The radiographic skeletal survey revealed agenesis of the ilio‐pubic rami with pubic dehiscence, right hip dislocation, bilateral coxa vara, short femurs, femoro‐tibial synchondrosis, bilateral hypoplastic tibiae more severe on the left side, and hypoplastic left calcaneus and talus. To the best of our knowledge, this combination of multiple congenital skeletal abnormalities has not been reported before. © 2002 Wiley‐Liss, Inc.
Predictive factors for suicidal ideation in patients with unresectable lung carcinoma
Authors: Akechi Tatsuo , Okamura Hitoshi , Nishiwaki Yutaka , Uchitomi Yosuke 
Published: October 2002

AbstractBACKGROUNDDespite serious concern over the suicidality of cancer patients in clinical oncology practice, few studies have addressed this issue. The purpose of the current study was to investigate the prevalence and predictive factors of suicidal ideation in patients with unresectable lung carcinoma in a follow‐up setting.METHODSPatients with newly diagnosed unresectable nonsmall cell lung carcinoma participated in this study. Their suicidal ideation was assessed 6 months after disclosure of the cancer diagnosis. Predictive factors for suicidal ideation were investigated by assessing a broad range of biomedical and psychosocial factors between the time of disclosure and start of cancer therapy (baseline) and 6 months after disclosure of the cancer diagnosis (follow‐up).RESULTSAlthough strong suicidal ideation was rare in this population, 13 (15%) of the 89 subjects who completed the baseline and follow‐up ratings had some degree of suicidal ideation 6 months after disclosure of the cancer diagnosis. Univariate analysis revealed that significant predictive factors for suicidal ideation were pain at baseline, declining physical function, and the development of a depressive disorder. Multivariate analysis indicated that pain at baseline (odds ratio [OR] = 3.72, 95% confidence interval [CI] = 1.12–14.69, P = 0.04) and the development of a depressive disorder (OR =27.97, 95% CI = 5.18–214.14, P = 0.0003) were the final significant predictive factors.CONCLUSIONSSuicidal ideation among unresectable lung carcinoma patients should not be neglected because it is not rare. Comprehensive care consisting of at least earlier pain management and appropriate psychiatric intervention is indispensable to prevent subsequent suicidal ideation. Cancer 2002;95:1085–93. © 2002 American Cancer Society.DOI 10.1002/cncr.10769
Metastatic prostate carcinoma to bone
Authors: Cheville John C. , Tindall Donald , Boelter Christopher , Jenkins Robert , Lohse Christine M. , Pankratz V. Shane , Sebo Thomas J. , Davis Brian , Blute Michael L. 
Published: October 2002

AbstractBACKGROUNDThe objective of this study was to examine the clinical and pathologic features of metastatic prostate carcinoma to bone in a large cohort of men, and the associations of these features with outcome.METHODSSixty‐eight men who underwent surgery for metastatic prostate carcinoma to bone for stabilization of a pathologic fracture or impending fracture were studied. Clinical characteristics included the type of treatment for the primary and metastatic prostate carcinoma, age and serum prostate specific antigen (PSA) at the diagnosis of the metastatic prostate carcinoma, radiographic findings of the metastasis (osteoblastic, osteolytic, or mixed), and the number of metastatic sites at the time of the surgery for the metastasis. Pathologic features examined included Gleason score of the metastatic prostate carcinoma. Immunohistochemical stains for MIB‐1, cytokeratin, PSA, synaptophysin, chromogranin A, serotonin, estrogen receptor, progesterone receptor, and androgen receptor were performed for all cases. The Kaplan–Meier method was used to estimate cancer‐specific survival. The duration of follow‐up was defined as the interval from the date of surgery for the metastasis to the date of death or last follow‐up. Univariate and multivariate Cox proportional hazards models were fit to assess the features that were associated with death from prostate carcinoma.RESULTSThe average (standard deviation) time from the surgery for the metastasis to death from prostate carcinoma was 1.5 (1.9) years, ranging from 0 days to 10 years, with a median of 1 year. The estimated cancer‐specific survival rates at 1 year, 2 years, and 3 years were 54.3%, 28.8%, and 22.9%, respectively. Median cancer‐specific survival occurred at 1.1 years. After 4 years of follow‐up, there were only seven patients left at risk for death from prostate carcinoma. Features that were found to be significantly associated with death from prostate carcinoma univariately included the interval between the diagnosis of metastasis and the surgery for metastasis (P < 0.001), androgen deprivation therapy before surgery for the metastasis (P = 0.002), presentation with metastasis (P = 0.003), the number of metastatic sites (P = 0.034), Gleason score of the metastasis (P = 0.002), and tumor positivity for chromogranin A (P = 0.041). On multivariate analysis, the interval between the diagnosis of metastasis and the surgery for metastasis (P < 0.001), Gleason score of the metastasis (P < 0.001), and tumor positivity for chromogranin A (P = 0.009) were associated significantly with death from prostate carcinoma.CONCLUSIONSAlthough cancer‐specific survival for patients after surgery for prostate carcinoma metastatic to bone is poor, assessments of tumor differentiation of the metastasis and chromogranin A positivity provide prognostic information. Cancer 2002;95:1028–36. © 2002 American Cancer Society.DOI 10.1002/cncr.10788
Telomerase activity and human telomerase reverse transcriptase mRNA expression are correlated with clinical aggressiveness in soft tissue tumors
Authors: Tomoda Ryota , Seto Masashi , Tsumuki Hideaki , Iida Koji , Yamazaki Takashi , Sonoda Jun , Matsumine Akihiko , Uchida Atsumasa 
Published: October 2002

AbstractBACKGROUNDTelomerase is a ribonucleoprotein enzyme that extends telomere specific repeats on the ends of chromosomes. Telomerase activity has been detected frequently in various types of human tumors and has been associated with cell immortality and oncogenesis. Human telomerase reverse transcriptase (hTERT), a telomerase catalytic subunit, reportedly regulates telomerase activity. Little is known about telomerase activity and hTERT mRNA expression in soft tissue tumors. The objective of this study was to clarify the correlation between these two parameters and clinical aggressiveness in soft tissue tumors.METHODSIn 41 surgically resected soft tissue tumors, telomerase activity was measured by the fluorescence‐based telomeric repeat‐amplification protocol and hTERT mRNA expression was determined by real‐time polymerase chain reaction.RESULTSTelomerase activity was detected in 52% of sarcomas and in none of the benign soft tissue tumors (P < 0.05). Telomerase activity was found in 77% of 13 locally recurrent sarcomas and in 89% of 9 sarcomas with distant metastasis. The frequency of the presence of telomerase activity in those tumors was significantly greater compared with the frequency of telomerase activity in the other sarcomas (P < 0.05 and P < 0.01, respectively). All telomerase positive sarcomas expressed hTERT mRNA. The mean level of hTERT mRNA expression in sarcomas was significantly greater compared with the mean hTERT mRNA expression level in benign tumors (P < 0.05) and in locally recurrent sarcomas compared with primary sarcomas (P < 0.001).CONCLUSIONSThe results of the current study suggest that the detection of telomerase activity and the level of hTERT mRNA expression are useful markers for evaluating the clinical aggressiveness in soft tissue tumors. Cancer 2002;95:1127–33. © 2002 American Cancer Society.DOI 10.1002/cncr.10793
Analysis of HIV‐1 variation in blood and semen during treatment and treatment interruption
Authors: Choudhury Bhudipa , Pillay Deenan , Taylor Stephen , Cane Patricia A. 
Published: October 2002

AbstractThe variability of populations of human immunodeficiency virus type 1 (HIV‐1) in blood and semen, with respect to envelope and polymerase gene sequences, was examined longitudinally in a patient experiencing treatment failure, interruption of treatment, and successful reintroduction of therapy. During treatment failure, there was little evidence of compartmentalisation between blood and semen, with virus with identical resistance‐associated mutations observed in both compartments and lack of clustering with respect to envelope gene sequences. After cessation of treatment, wild‐type virus became the predominant population, displaying distinct envelope gene populations, indicating that wild‐type virus had overgrown the resistant virus, rather than the resistant virus reverting to wild‐type. Once successful therapy had been recommenced, it was possible to distinguish distinct populations of virus in the two compartments. These data support the hypothesis that the male genital tract represents a distinct HIV‐1 reservoir. J. Med. Virol. 68:467–472, 2002. © 2002 Wiley‐Liss, Inc.
Platinum agents in the treatment of osteosarcoma: Efficacy of cisplatin vs. carboplatin in human osteosarcoma cell lines
Authors: Robson H. , Meyer S. , Shalet S.M. , Anderson E. , Roberts S. , Eden O.B. 
Published: October 2002

AbstractBackgroundCisplatin (cDDP), when used either alone or, more often, in combination with other agents, especially adriamycin, achieves a high response rate in osteosarcoma. Its use, however, is limited by severe nephro‐ and neuro‐toxicity. Second generation platinum compounds, most notably carboplatin (CBDCA), have been developed in order to attempt to reduce these dose‐limiting toxicities, and thus improve the therapeutic ratio. Studies evaluating the role of combination CT containing CBDCA vs. cDDP have demonstrated differing results depending on the tumor type tested and its role in the treatment of osteosarcoma has yet to be clarified.ProcedureIn this study, we compared the in vitro anti‐tumor activity of cDDP and CBDCA in a panel of three human osteosarcoma cell lines (HOS, MG63, and U2OS).ResultscDDP and CBDCA (0–20 μmol) showed marked variation in cytotoxicity among the three cell lines. EC50 values for CBDCA in HOS and MG63 cells were approximately two‐fold higher than for cDDP and the ratio of AUCCBDCA to AUCcDDP varied from 1.8 in the HOS cell line to 2.3 in the MG63 cell line. Exposure of MG63 and HOS cells to either cDDP or CBDCA (1.67 and 13.5 μmol) caused a G2/M cell cycle arrest by 24 hr. Also evident was a sub G1 peak indicative of cell death by apoptosis. U2OS cells were relatively resistant to the cytotoxic effects of both drugs, although a cell cycle arrest in response to DNA damage was observed. This suggests that unlike MG63 and HOS cells, U2OS cells have either a more efficient repair pathway for platinum‐induced DNA damage or are able to evade apoptosis. Examination of apoptotic events and cellular recovery demonstrated that both an 8–16‐fold higher concentration and longer treatment period for CBDCA compared with cDDP was required to produce equivalent cell death and a loss of the ability of single cell clones to form colonies in both the HOS and MG63, but not the U2OS cell line.ConclusionsOur findings suggest that CBDCA at a two‐ to four‐fold higher concentration than cDDP has potential therapeutic activity in platinum sensitive osteosarcomas, particularly when cDDP cytotoxicity compromises therapeutic efficacy. Med Pediatr Oncol 2002;39:573–580. © 2002 Wiley‐Liss, Inc.
Improving perishable product inventory management using goal programming
Authors: Kendall Kenneth E. , Lee Sang M. 
Published: October 2002

AbstractThe multiple objectives of perishable product inventory management are examined in this paper. These objectives include: (1) satisfying demand by carrying sufficient inventories, (2) holding down inventory carrying costs, (3) keeping the amount of product spoilage (outdating) at an acceptable level, and (4) maintaining quality by using the product while it is still fresh, and (5) keeping the cost of rotation low. Some of the above objectives are in conflict. Thus, certain redistribution policies may help attain one or more of these objectives to a greater extent. Redistribution involves the transfer of the product from outlets where demand is low to outlets where demand is high. A goal programming model for solving redistribution problems is presented. An example is provided and sensitivity analysis is performed in order to determine when redistribution is advantageous. Applicability of the model is discussed.
A heuristic method for aggregate planning: Production decision framework
Authors: Holt Jack A. 
Published: October 2002

AbstractThis paper presents an understandable and straight‐forward method for making work force level and inventory planning decisions, i.e., dynamic aggregate planning decisions.The development phase utilizes a ratio, named RPCC, which represents the relative value of the cost of changing the production level to the cost of carrying inventory. This ratio is used to determine the length of an effective planning horizon. Two indicators are calculated to reflect the demand to current production rate over different time periods. Based on the joint values of these indicators, the planning problem is subdivided into one of nine mutually exclusive and exhaustive states. A set of action statements, representing logical responses to each of the sub‐problems, is formulated.After completion of the development phase, the performance of the Production Decision Framework model is tested in several real case environments. Suggestions are made for further improvement.