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Introduction and aim: Pancreatic cancer is considered one of the most aggressive solid tumors. In Mexico, it is the twelfth cause of cancer, with 4,489 cases diagnosed annually, and accounts for 4.9% of oncologic deaths. Aim: The aim of our study was to describe the clinical and epidemiologic characteristics of the patients diagnosed with pancreatic cancer spanning an 11-year period at the Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”. Methods: A retrospective, cross-sectional study was conducted that included 479 patients diagnosed with pancreatic cancer, within the time frame of 2003-2013. The documented findings were summarized through descriptive statistics. Results: Of the patients with pancreatic ductal adenocarcinoma, 50.9% were women, and the mean patient age at diagnosis was 61.5 years. A total of 48.4% of the cases were diagnosed at clinical stage IV, 12.9% presented with clinical stage III, and 25.0% had localized disease. Surgery was performed on 37.5% of the patients, the most frequent of which was pancreatoduodenectomy. The surgical mortality rate was 5.5%. Conclusion: The clinical characteristics in our study group were similar to those described in the literature. However, the number of candidates for surgical treatment was higher than that reported in other hospitals and the percentage of borderline tumors was lower. Those differences, respectively, are possibly associated with the nature of our referral center and the prolonged intervals between diagnosis and treatment that result in the loss of potential surgical patients. Resumen: Introducción y objetivo: El cáncer de páncreas es considerado uno de los tumores sólidos más agresivos. En México representa la doceava causa de cáncer con 4,489 casos diagnosticados por año y representa el 4.9% de las defunciones oncológicas. El objetivo del estudio es describir las características epidemiológicas y clínicas de los pacientes con diagnóstico de cáncer de páncreas en un periodo de once años del Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”. Métodos: Estudio retrospectivo – transversal que incluyó 479 pacientes con diagnóstico de cáncer de páncreas en el periodo 2003 - 2013. Se incluyó estadística descriptiva para resumir los hallazgos documentados. Resultados: De los pacientes con adenocarcinoma ductal de páncreas el 50.9% fueron mujeres, la edad promedio al diagnóstico fue de 61.5 años. Se diagnosticaron en un estadio clínico IV el 48.4 % de los casos, mientras que el 12.9% se presentaron como estadio clínico III y el 25.0% como enfermedad localizada. El 37.5% de los pacientes fueron sometidos a cirugía, siendo la pancreatoduodenectomía el procedimiento más frecuentemente realizado. La mortalidad quirúrgica fue del 5.5%. Conclusión: Las características clínicas en nuestro grupo de estudio muestran similitud con la literatura, sin embargo, el número de candidatos a un tratamiento quirúrgico fue superior a las cifras reportadas en otros hospitales, no obstante, la cifra de tumores limítrofes fue menor; probablemente asociado con la naturaleza de centro de referencia que representa nuestra institución, así como a la pérdida de pacientes potencialmente quirúrgicos debido a un periodo de ventana prolongado entre diagnóstico y tratamiento.

Resumen Introduccion y objetivo El cancer de pancreas es considerado uno de los tumores solidos mas agresivos. En Mexico representa la decimosegunda causa de cancer con 4,489 casos diagnosticados por ano y representa el 4.9% de las defunciones oncologicas. El objetivo del estudio es describir las caracteristicas epidemiologicas y clinicas de los pacientes con diagnostico de cancer de pancreas en un periodo de once anos del Instituto Nacional de Ciencias Medicas y Nutricion «Salvador Zubiran». Metodos Estudio retrospectivo-transversal que incluyo 479 pacientes con diagnostico de cancer de pancreas en el periodo 2003-2013. Se incluyo estadistica descriptiva para resumir los hallazgos documentados. Resultados De los pacientes con adenocarcinoma ductal de pancreas el 50.9% fueron mujeres, la edad promedio al diagnostico fue de 61.5 anos. Se diagnosticaron en un estadio clinico IV el 48.4% de los casos, mientras que el 12.9% se presentaron como estadio clinico III y el 25.0% como enfermedad localizada. El 37.5% de los pacientes fueron sometidos a cirugia, siendo la pancreatoduodenectomia el procedimiento mas frecuentemente realizado. La mortalidad quirurgica fue del 5.5%. Conclusion Las caracteristicas clinicas en nuestro grupo de estudio muestran similitud con la literatura, sin embargo, el numero de candidatos a un tratamiento quirurgico fue superior a las cifras reportadas en otros hospitales, no obstante, la cifra de tumores limitrofes fue menor; probablemente asociado con la naturaleza de centro de referencia que representa nuestra institucion, asi como a la perdida de pacientes potencialmente quirurgicos debido a un periodo de ventana prolongado entre diagnostico y tratamiento.

Objectives By deploying a novel combination of machine learning approaches, we aim to investigate the contributions of each local and systemic risk factors in multi-etiology of knee osteoarthritis (KOA) to disease onset and deterioration. Methods A machine-learning-based KOA progression prediction model is developed using the data from the National Institute of Health Osteoarthritis Biomarkers Consortium. According to Kellgren-Lawrence (KL) grade of plain radiographs at baseline, the subjects are divided into either KOA onset or deterioration study groups. The disease progression is defined as the changes in both joint space width (JSW) and WOMAC pain score. In addition to radiographic and symptomatic data, the anthropological particulars, history of the knee injury and surgery, metabolic syndrome and living habits were deployed in a multi-layer perceptron (MLP) to predict disease progression in each study group. The relative contributions of each risk factors were weighted via DeepLIFT gradient. Additionally, statistical interactions among risk factors were identified compared. Results Our model achieved AUC of 0.843 (95% CI 0.824, 0.862) and 0.765 (95% CI 0.756, 0.774) in prediction of KOA onset and deterioration, respectively. For KOA onset prediction, history of injury has attained the highest DeepLIFT gradient except medial joint space narrowing; while for KOA deterioration prediction, diabetes and habit of smoking obtained second and third highest gradients respectively aside from medial joint space narrowing, surpassing the impact of the injury. Conclusion We developed a machine learning workflow which effectively dissects the risk factors’ contributions and their mutual interactions for onset and deterioration of KOA respectively.

e16181 Background: Immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) are widely adopted in contemporary advanced HCC (aHCC) treatment algorithms. Nevertheless, the optimal strategy for treatment after ICI exposure is unknown. We evaluated the pattern of use, response, survival and safety of TKIs in aHCC patients who previously received ICIs. Methods: We performed an international, multi-centre study of aHCC patients who received TKIs after prior treatment with ICIs. Objective response rate (ORR), disease control rate (DCR), time-to-progression (TTP), overall survival (OS) and adverse events (AE) were assessed. Results: Between January 2015 and December 2020, one-hundred and forty-eight patients were included. The median age was 63 (range 29-84) and 78.4% were of Child-Pugh Grade A. 75.7% had hepatitis-B related HCC. 64.9% received TKI as single agent and 35.1% received TKI in combination with other agents. 75% who received TKI combinations had concomitant ICIs. 48.6% had prior TKIs. The median follow-up was 23.3 months. For single agent TKI patients, the ORR was 14.6%, DCR was 38.5%, median TTP was 3.9 months (95% C.I. 3.3-4.5) and median OS was 8.6 months (95% C.I. 5.8-11.4). For patients receiving TKI combinations, the ORR was 25%, DCR was 38.5%, median TTP was 3.5 months (95% C.I. 1.7-5.2) and median OS was 15.1 months (95% C.I. 5.7-24.5). There were no significant differences in ORR, DCR and median OS between patients who had primary resistance to prior ICI compared to those with acquired ICI resistance and between those who were TKI-naive compared to those who were TKI-exposed. Notably, patients who received TKI-ICI combinations had significantly superior survival compared to single agent TKI patients (median OS 15.1 months (95% C.I. 6.7-23.5) vs. 8.6 months (95% C.I. 5.6-11.7), p = 0.011) but not significantly superior ORR, DCR or TTP. Amongst patients who received single agent TKI and were naive to both sorafenib and lenvatinib, those who received lenvatinib had significantly superior DCR, TTP and OS compared to those who received sorafenib (DCR 51.5% vs 25.8%, p = 0.035; median TTP 6.3 months (95% C.I. 3.0-9.7) vs. 1.8 months (95% C.I. 0-3.6), p = 0.003; median OS 12.0 months (95% C.I. 7.0-17.0) vs. 5.9 months (95% C.I. 1.9-10.0), p = 0.008). 70.3% and 15.5% of all patients, and 77.1% and 15.6% of patients who received single agent TKI experienced all grade and grade ≥3 AEs respectively. The most common AEs were hand foot syndrome, skin rash and diarrhea. Conclusions: TKIs can achieve encouraging anti-tumour response and survival outcomes with acceptable safety in prior ICI-treated aHCC patients. Moreover, TKI-ICI combinations were associated with better survival than single agent TKIs. Notably, among patients who received single agent TKIs, lenvatinib had significantly better responses and survival results than sorafenib.

Objective/Background The reliability and validity of the Chinese version of the Kid-KINDLR questionnaire were examined with school-aged children in Hong Kong. Methods A total of 112 healthy children were selected by convenience sampling from two primary schools and 30 children with global developmental delay were selected from an outpatient occupational therapy department of a convalescent hospital. The Kid-KINDLR questionnaire was translated using independent forward and backward translation. The content validity of the translated instrument was evaluated by four experts. Internal consistency, factor analysis, and construct validity were examined in the healthy children group, whereas known-group comparison was performed in the group with global developmental delay. Results The significance value of the Shapiro—Wilk test was greater than 0.05, indicating that the sample displayed a normal distribution. The total score had good internal consistency (Cronbach's alpha = .77); however, the consistency of the subscales varied (Cronbach's alpha ranged from .47 to .70). The children and parent questionnaires did not load onto the six factors originally hypothesized. Instead, seven factors were generated. Evidence supporting the questionnaire's validity included a lack of age and sex bias and positive known-group differentiation (Wilks’ lambda = 0.906, p = .035). Conclusion The Chinese version of the Kid-KINDLR questionnaire exhibited good psychometric properties, but the internal consistency of the translated instrument needs further improvement. It is recommended that practitioners focus on the Kid-KINDLR total score when interpreting the Kid-KINDLR data. Overall, the study findings indicate that the Chinese version of the Kid-KINDLR is an important tool for use in clinical practice.

Background Dyspnoea is crucial in evaluating patients with chronic obstructive pulmonary disease (COPD). The San Diego Shortness of Breath Questionnaire (UCSD SOBQ) assesses shortness of breath in activities of daily living (ADL). It has been translated into Chinese and used clinically in Hong Kong for many years. Objective To investigate the reliability and validity of a self-administered Chinese version of the Shortness of Breath Questionnaire (C-SOBQ) with pictorial enhancement in patients with COPD in Hong Kong. Methods A total of 119 patients with COPD were recruited by convenience sampling from seven public clinical settings and two community self-help groups. The C-SOBQ score for each patient was correlated with a set of criterion parameters including age, body mass index (BMI), 6-minute walking distance (6MWD) test, lung function physiological parameters, BODE index, the Modified Medical Research Council Dyspnoea Scale (MMRC Dyspnoea Scale), and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD classifications. For test–retest reliability, 22 out of 119 patients were selected and assessed using the C-SOBQ followed by a reassessment within 1 week by the same rater. Results The C-SOBQ shows good test–retest reliability with an intra-class correlation coefficient of 0.915 (p ≤ .05). It demonstrates significant correlations with the MMRC Dyspnoea Scale, GOLD COPD classifications, BODE index, BMI, and 6MWD. The BODE index, MMRC Dyspnoea Scale, and 6MWD were valid predictors of C-SOBQ total score. A total of 50.4% of patients could be correctly grouped in quartiles of the BODE index using the C-SOBQ. Conclusion The C-SOBQ with pictorial enhancement is a valid and reliable instrument which gives precise information about the impact of dyspnoea on functional activities for patients with COPD.

Objective The chronic respiratory questionnaire (CRQ) is used by occupational therapists to measure patients' quality of life in pulmonary rehabilitation programmes in Hong Kong. In this study, we developed the Chinese version of the chronic respiratory questionnaire (CCRQ), and investigated its content validity and reliability. Methods A forward and backward translation method was adopted, with detailed analysis of the relevance, importance and linguistic equivalence by an expert panel. Test-retest reliability and internal consistency of the CCRQ were assessed on 37 and 118 local Chinese chronic obstructive pulmonary disease patients from multicentres, respectively. Results It was found that the content validity of the CCRQ was supported by the opinions from the respiratory experts. The degrees of agreement in the linguistic analyses were high for all items including the activity list and the rating scale. Strong test-retest correlations and high internal consistency were found in the reliability testing. Conclusion The CCRQ is a valid and reliable instrument for measuring the health status of patients with chronic respiratory diseases in the local population.

OBJECTIVE. The reliability and validity of the Test of Visual-Perceptual Skills (Non-Motor)–Revised (TVPS–R) were examined for its usefulness on Hong Kong Chinese preschoolers. METHOD. Content validity was evaluated by six experts. Test–retest reliability, construct validity, and criterion validity were examined on 66 typically developing preschoolers while concurrent validity was examined on these preschoolers plus 52 preschoolers with visual-perception difficulties. RESULTS. Test–retest reliability was high for the total score (intraclass correlation coefficient [ICC] =.88), but not for all subtests (ICC ranged .38 to .77) or for individual items (mean kappa = 0.32). The standard error of measurement (SEM; 1.53) and internal consistency (Cronbach’s alpha = .90) were satisfactory. Evidence supporting the test’s validity included a significant developmental trend (F = 4.99, p < .001), a lack of gender bias (F = .04, p = .84), and positive known-group differentiation (Wilks’s lambda = 52.42, p < .001). The correlation between the Motor-Free Visual-Perceptual Test–Revised composite score and the TVPS–R composite was moderate at r = .60. CONCLUSIONS. When based on the total scores, the TVPS–R was reliable and valid. The use of subtest scores and item scores for decision making or treatment planning is not recommended.

Background Previous studies have shown that 10–30% haemodilution with crystalloid may induce a hypercoagulable state demonstrable by using the Thrombelastograph® (TEG). While most are in vitro studies, the few in vivo studies are limited by confounding surgical or ‘environmental' factors. We conducted this randomized controlled study to evaluate the coagulation changes associated with in vivo haemodilution. Methods Twenty patients undergoing major hepatobiliary surgery were randomly allocated to one of two study groups. Group H (n=10) had 30% blood volume withdrawn over 30 min and replaced with saline. Group C (n=10) did not have any blood withdrawn. Blood samples were taken in both groups at 10, 20 and 30 min. Native TEG, complete blood count, coagulation profile, fibrinogen, antithrombin III, protein C and thrombin–antithrombin complex concentrations were measured. Results Compared with Group C, Group H patients had significantly greater shortening of r-time at 30 min (–30% vs +36%), greater shortening of k-time at all time points (–36% vs +17% at 10 min; –37% vs +44% at 20 min; –45% vs +49% at 30 min), and greater widening of α at 30 min (+71% vs +4%). The decrease in antithrombin III and other natural procoagulants and anticoagulants closely followed that of haematocrit, with the exception of thrombin–antithrombin complex. Conclusion In vivo haemodilution of up to 30% with saline can induce a hypercoagulable state. The mechanism remains unclear as disproportionate dilution of natural anticoagulants was not detected. Thrombin–antithrombin complex concentration remained stable despite haemodilution in Group H, which may suggest increased thrombin generation.

This article describes the development of a new functional measure — the Monitored Functional Task Evaluation (MFTE) — a symptom-limited evaluation that is used to measure the functional performance of an individual with chronic obstructive pulmonary disease (COPD), and to document a client's physiological changes through repeated testing. Stage I of the study included developing the content validity of the instrument. Stage II consisted of establishing the performance profile, test-retest and inter-rater reliability using a convenience sample of 27 inpatients and outpatients who had COPD. In stage III, the criterion-related and discriminative validity of the instrument was verified in a retrospective sample of 124 inpatients and day patients who had COPD. Results indicated that there was high intra- and inter-rater reliability for the total score of MFTE. Significant correlation of the MFTE was found with parameters such as Moser's Activities of Daily Living (ADL) class, COPD disability class, 6-minute walking distance, work capacity in terms the ratio of the metabolic rate associated with a given activity to the resting metabolic rate, and the fatigue dimension of the Chronic Respiratory Disease Questionnaire. In addition, prediction of group membership to Moser's ADL class revealed that 52.4% of the original grouped cases could be correctly classified by the MFTE alone. In conclusion, the MFTE is a useful measure to evaluate functional performance as well as document physiological changes in patients with moderate-to-severe COPD from both conceptual and empirical perspectives.

Three novel splice site mutations and two novel missense mutations were identified by molecular analysis of pyruvate kinase (PK) deficiency associated with hereditary nonspherocytic hemolytic anemia. A Nepalese PK variant, PK Kowloon, was found to have a homozygous transversion at the 5′-splice site of the seventh intervening sequence (IVS) of the L-type PK gene (Ivs7[+1]gt → tt). Using a reverse transcription polymerase chain reaction (RT-PCR) assay, we showed that the R-type PK mRNA in the proband's reticulocytes included the seventh IVS between the seventh and eighth exon, introducing a stop codon 3 nucleotides downstream of the mutated site. Consequently, the translational product may lack 44% of the R-PK polypeptide. A transition at the last nucleotide of exon 9 (1269GCG → GCA) was found in a Japanese PK variant, PK ‘Kamata.’ The mutation did not alter the amino acid sequence, but caused skipping of the ninth exonic sequence in the R-PK transcripts. As a result, the affected R-type PK lost 51 amino acid residues (373Met-423Ala del). A transversion at the splice acceptor site of the third IVS (Ivs 3[-2]ag → tg) was identified in PK ‘Aomori.’ The mutation resulted in aberrant splicing at a cryptic splice site within exon 4, causing deletion of two codons in the aberrant R-PK transcript (95 Gly-96 Pro → del). Both PK ‘Kamata’ and PK ‘Aomori’ had a missense mutation on the other allele, 1044AAG → AAT (348Lys → Asn) and 1075CGC → TGC (359Arg → Cys), respectively. Although both 348Lys and 359Arg were located in the sixth loop of A domain (β/α)8 barrel, which has been shown to contain the substrate and cation binding sites, the degree of anemia was much more severe in PK ‘Kamata’ than PK ‘Aomori,’ possibly because the 51 amino acid deletion of PK ‘Kamata’ but the 2 amino-acid deletion of PK ‘Aomori’ may abolish PK catalytic activity.

The c- kit proto-oncogene encodes a transmembrane tyrosine kinase receptor. It is expressed by the primitive CD34 positive haemopoietic stem cells and interacts with the Kit ligand for signal transduction. It was reported to be expressed in over 80% of acute myelogenous leukaemia (AML) patients in North America and Japan. We analyzed 20 AML patients for c- kit expression using either Northern blot analysis or flow cytometry with the YB5.B8 anti-c- kit antibodies. Only 6 out of 20 AML patients expressed the c- kit mRNA or protein product. However, a previously unreported abnormal sized 1.7–1.9 kb transcript was detected in the blast cells of 1 AML patient, 1 acute mixed lineage leukaemia patient and 1 chronic myelogenous leukaemia (CML) patient in myeloblastic transformation. Our data suggested that in most Hong Kong Chinese AML patients, leukaemia transformation may have occurred at a c- kit negative stage. Alternatively, the abnormal sized c- kit transcript that was detected in some Chinese myeloid leukaemia patients may represent an aberrant c- kit receptor that plays an important role in leukaemogenesis.

It is interesting that the higher rate of public concern and lack scientific research on riding techniques of speed horse race compare with equestrian. In this study, riding postures of different class jockeys were tested under varied speeds by means of simulation horse to explore a simple way of evaluating jockey's posture control ability.

A Chinese family with concurrent hereditary spherocytosis (HS) and haemoglobin (Hb) Q-Thailand is described. The Hb Q-Thailand mutation was found on the remaining alpha1 globin gene on a chromosome 16 containing the (-alpha 4.2) deletion. Active haemolysis in members of this family is segregated with the HS phenotype, and the Hb Q-Thailand in the heterozygous state does not seem to show any modulating effect on HS.

Three major types of mRNA can be expressed as a result of the Philadelphia translocation, dependent on the position of the break within the BCR gene on chromosome 22. In addition, alternative splicing of the mRNA transcribed from the BCR/ABL fusion gene has been reported and it has been suggested that this may play a role in the generation of the acute phase of Philadelphia positive chronic myeloid leukaemia (CML). We have examined the fusion RNA present in 24 cases of chronic phase CML and 21 cases of patients with CML in blast crisis using the polymerase chain reaction. In no case was it possible to detect the presence of the e1a2 junction which encodes the p190 hybrid protein product. We conclude that the acquisition of the p190 does not play a significant role in the generation of the blast crisis of CML. Neither could we detect a significant difference in the number of cases which simultaneously express both b2a2 and b3a2 junction products in samples isolated from chronic phase and blast crisis. In the series analysed by ethidium bromide stained gels, there was, however, an increase in the percentage of cases expressing the b3a2 junction in the mononuclear cells of blast crisis patients as compared to the white blood cells of patients in chronic phase.

Background Age-related skewing of X-chromosome inactivation leading to glucose-6-phosphate dehydrogenase (G6PD) deficiency in elderly women in a population with prevalent G6PD gene mutations was investigated. Methods G6PD activity was measured biochemically. G6PD mutations were detected by polymerase chain reaction (PCR) and allele-specific extension, and analyzed by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry and Sequenom MassARRAY. X-chromosome inactivation was quantified by semiquantitative PCR for the HUMARA gene, before and after HpaII digestion. Results In 173 women (median age: 90 years; range, 80-107 years), 18 heterozygotes for G6PD mutations were identified. Three heterozygotes were G6PD deficient, owing to skewed X-chromosome inactivation affecting the wild-type allele. Fifteen heterozygotes, with skewing apparently affecting the mutant alleles, had normal but significantly lower G6PD levels. At 1.73%, G6PD deficiency was significantly more frequent than expected from population screening at birth. Conclusion Due to skewed X-chromosome inactivation, elderly women in populations with prevalent G6PD mutations are at risk of G6PD deficiency.

The capability of subsurface target identification at shallow depths has been demonstrated using an electromagnetic video or base-band pulse radar. Real radar measurements were collected for five targets at a depth of 5 cm (2 in) in various ground conditions. These measurements were processed for target characterization and identification. Identification performance based on a single radar observation was evalualted. The identification process requires only simple algebraic operations and thus offers the potential of real-time on-location identification of subsurface targets.

Blast cells from a majority of acute myelogenous leukaemia (AML) patients express c-kit mRNA. However, c-kit expression has not been observed in patients with acute lymphoblastic leukaemia (ALL) and lymphoproliferative disease. We report here the detection of an abnormal sized c-kit mRNA in two Hong Kong Chinese patients with pre-B ALL and common ALL.

Routing in wireless ad-hoc networks has received significant attention in the literature due to the fact that the dynamic behavior of these networks poses many technical challenges on the design of an effective routing scheme. Though on-demand routing approaches have been shown to perform well, they generally lack the support for quality-of-service (QoS) with respect to data transmission. In order to select a subset of end-to-end paths to provide increased stability and reliability of routes, a new QoS metric, end-to-end reliability, is defined and emphasized. We present a distributed multi-path dynamic source routing protocol (MP-DSR)for wireless ad-hoc networks to improve QoS support with respect to end-to-end reliability. Our protocol forwards outgoing packets along multiple paths that are subject to a particular end-to-end reliability requirement. A simulation study is performed to demonstrate the effectiveness of our proposed protocol, particularly the fact that MP-DSR achieves a higher rate of successful packet delivery than existing best-effort ad-hoc routing protocols, such as the dynamic source routing (DSR).

We investigated whether in normal subjects isokinetic concentric and eccentric strength variables were related in order to have a better picture in relation to rehabilitation and possible injury prevention. We studied the relationship between isokinetic concentric and eccentric peak torque, total work, and average power of knee extension and knee flexion at 60 degrees/sec and 120 degrees/sec in 42 young Chinese adults (22 males, age = 27 +/- 6.9 years; 20 females, age = 24.9 +/- 5.05 years) using the Cybex 6000 isokinetic dynamometer. Repeated analysis of covariance was used to compare the means between concentric and eccentric variables adjusted by limb dominance, speed of testing, and the muscle groups tested. A highly significant correlation was found between all concentric and eccentric variables, with correlation coefficients (r) ranging from 0.67 to 0.93. All but two of the eccentric variables were significantly greater than the concentric variables. Concentric and eccentric knee flexion to knee extension (H:Q) ratios were poorly correlated, with r ranging from 0.359 to 0.645. Although there is an acceptably high correlation between isokinetic concentric and eccentric strength variables of knee flexion and extension in young healthy individuals, we recommend measuring concentric and eccentric strength to plan a proper rehabilitation program and to assess muscle groups in a given contraction mode.

We identified four distinct point mutations in homozygous pyruvate kinase (PK) variants in Japanese and Chinese patients with chronic nonspherocytic hemolytic anemia. All gene abnormalities were missense mutations that caused single amino acid substitutions. 1261A (Q421K) and 1436A (R436H), which were identified in PK Sendai and PK Shinshu, had been found in unrelated Japanese and Amish PK variants, respectively. The clinical severity and extremely low residual erythrocyte PK activity of PK Shinshu as well as of the Amish PK might be caused partly by aberrant splicing, because the 1436A mutation changes a nucleotide at the last nucleotide in the exon 10. Recently, we diagnosed a 42-year-old Japanese woman with chronic nonspherocytic hemolytic anemia as having a homozygous PK deficiency. DNA sequencing of the variant PK gene showed a homozygous missense mutation at 1403GCT- ->GTT, resulting in a single amino acid substitution from 468la-->Val. The gene mutation is likely to impair the allostericity of this enzyme, speculated from the tertiary structure. A homozygous missense mutation in PK Hong Kong, a boy of a non-Han southern Chinese minority group, was identified in exon 7 of the human L-PK gene, 941ATT-->ACT, resulting in a single amino acid substitution from 314lle-->Thr. The R- PK activity is expected to be severely affected, because the mutated amino acid residue is located between the 313 Lys and the 315 Glu, which are very important for acid-base catalysis and magnesium binding, respectively. Both the R- and M2-type PK were shown by polyacrylamide gel electrophoresis of the PK Hong Kong erythrocyte lysate, and this is the first report of a homozygous individual whose erythrocytes contain the immature (M2)-type isozyme.

Twenty-seven new patients with advanced nasopharyngeal carcinoma were evaluated by marrow biopsy at diagnosis. The marrow trephines and blood clots were evaluated by morphology and immunohistochemical studies for cytokeratin and found negative in all cases. The median follow-up of this group of 27 patients was 22 months, and 7 of them had relapsed in the skeletal system. We conclude, in view of its poor sensitivity, that routine use of marrow biopsy for the staging of nasopharyngeal carcinoma is not recommended.

Childhood acute lymphoblastic leukemia (ALL) is a biologically diverse malignancy. The major subsets correspond to B or T precursor cells, although some ALL may originate in lympho—myeloid stem cells. Multiple molecular alterations contribute to the pathogenesis of ALT., including some that are subset specific. In those cases (~5%) with a Philadelphia chromosome, the genetic basis of karyotypic alteration and the resultant activated ABL kinase have been determined and offer new strategies for molecular diagnosis and monitoring. Although these changes at the DNA level are likely to be functionally relevant to the underlying mechanisms of leukemogenesis, the etiology of childhood ALL remains an enigma. A hypothesis is proposed that takes into account geographic and time trend variations in incidence rates, unusual properties of lymphocyte precursors, and promoting effects of immune responses in infancy.

The chromosome 22 derivative, the Philadelphia (Ph) chromosome, results from a reciprocal translocation t(9;22) (q34;q11) and is associated with chronic myeloid leukemia (CML). The translocation can be identified at the DNA level in Ph-positive CML by using a probe to the breakpoint cluster region (bcr). In addition, as a result of this translocation an abl-related 210-kd protein with protein tyrosine kinase (PTK) activity is produced. We analyzed 28 cases of Ph-negative CML for rearrangement of the chromosome 22 sequences and found that eight of the 28 show rearrangement of the bcr. When 12 of the Ph- negative cases were independently reviewed, five were indistinguishable from Ph-positive CML on the basis of morphology, peripheral blood film and clinical details. These five also showed bcr rearrangement. The other seven were reclassified as six atypical CML (aCML) and one chronic myelomonocytic leukemia (CMML). None of these seven showed bcr rearrangement. In addition 11 cases of bcr- CML were assayed for abl- related PTK, and no detectable activity was present, whereas p210 phl/abl PTK was observed both in Ph-positive (three cases examined) and Ph-negative, bcr + (four cases examined) CML. Therefore, bcr + CML, whether or not the Ph chromosome is cytogenetically apparent, involves a similar molecular alteration and produces the 210-kd protein with enhanced PTK activity. Furthermore, these cases can be distinguished from Ph-negative bcr- CML by careful evaluation of clinical and hematologic data.

The diagnostic value of a panel of monoclonal antibodies was assessed in 100 consecutive patients with acute leukaemia. 97 patients were clearly phenotyped. Clinical and haematological feedback showed that the immunological data made a critical contribution to the final haematological diagnosis in 19 patients and provided useful confirmatory data in another 78. Immunophenotype also provided the basis for a subset classification of known prognostic relevance to acute lymphoblastic leukaemia (ALL). Immunophenotype and haematological findings conflicted in 2 cases, and 3 cases were unclassifiable with the antibody panel. In these difficult cases leukaemic-cell DNA was investigated for immunoglobulin gene rearrangement. Immunophenotyping with selective probes may be used in conjunction with other laboratory analyses (eg, karyotyping) in the routine investigation of patients with acute leukaemia.

Accumulating evidence suggests that the therapeutic margin of aminoglycoside therapy may be improved by manipulation of dosing strategy. Recent understanding of concentration-dependent bactericidal activity and postantibiotic effect argues that the aminoglycosides may be administered in larger doses and at longer dosing intervals than currently recommended without compromising efficacy. Preliminary clinical experience suggests that once-daily regimens are as efficacious as conventional intermittent injections in the treatment of gram-negative infections including urinary tract infections, cystic fibrosis, and bacteremia in nonneutropenic patients. The transient, high peak serum concentrations achieved in once-daily dosing have not been associated with excessive nephrotoxicity or ototoxicity thus far. Decreased accumulation in renal cortex as a result of saturable renal uptake after the single daily dose may even reduce the incidence or severity of renal damage. Further studies on more patients are required to substantiate these preliminary findings.

The Philadelphia (Ph) chromosome breakpoints in chronic myelocytic leukaemia are clustered on chromosome 22 band q11 in a 5.8-kilobase (kb) region designated bcr. The c-abl protooncogene is translocated from chromosome 9 band q34 into bcr and the biochemical consequence of this molecular rearrangement is the production of an abnormal fusion protein bcr-abl p210 with enhanced protein-tyrosine kinase activity compared to the normal p145 c-abl protein. The Ph chromosome translocation is also seen in some acute lymphoblastic leukaemias with B-cell precursor phenotypes some of which have bcr rearrangement (bcr+) and some do not (bcr-). We present evidence that the Ph+, bcr- leukaemias are associated with a novel p190 abl kinase. We propose that acute lymphoblastic leukaemias that are bcr+, p210+ are probably lymphoid blast crises following a clinically silent chronic phase of chronic myelocytic leukaemia arising in multipotential stem cells whereas bcr-, p190+ cases are de novo acute lymphoblastic leukaemias arising in more restricted precursors.

Summary. Monosomy 7 was the sole karyotypic abnormality seen in a case of biphenotypic leukaemia involving both the myeloid and lymphoid lineages and in a case of de novo ALL undergoing a phenotypic shift to acute myeloid leukaemia at relapse. These observations suggest that monosomy 7 can be associated with transformation of a common lymphoid-myeloid progenitor cell.