Microsatellite instability and mutation analysis of hMSH2 and hMLH1 in patients with sporadic, familial and hereditary colorectal cancer

To date, at least four genes involved in DNA mismatch repair, hMSH2, hMLH1, hPMS1 and hPMS2, have been demonstrated to be altered in the germline of patients with hereditary nonpolyposis colorectal cancer (HNPCC). Additionally, defective mismatch repair is thought to account for the observation of microsatellite instability (MIN) in tumors from these patients. The genetic defect responsible for the MIN+ phenotype in sporadic colorectal cancer, however, has yet to be clearly delineated. In order to better understand the role of somatic and germline alterations within hMSH2 and hMLH1 in the process of colorectal tumorigenesis, we examined the entire coding regions of both of these genes in seven patients with MIN+ sporadic colorectal cancer, 19 patients with familial colorectal cancer, and 20 patients meeting the strict Amsterdam criteria for HNPCC. Thirteen germline, two somatic, and four neutral alterations were identified. The two somatic mutations occurred in patients having familial cancer, while the germline mutations were distributed among one sporadic (14%), three familial (16%), and nine HNPCC (45%) cases. All patients with identified mutations in the mismatch repair genes, whose tumors were available for analysis, demonstrated MIN. On the other hand, we could not identify mutations in the subset of clinically defined HNPCC patients with MIN negative tumors nor in the majority (6/7) of MIN+ sporadic tumors.      

贴耳穴治疗慢性鼻炎35例的疗效

０　引言　慢性鼻炎是一种常见的多发病．中医认为,人体卫气不固之时感受外邪而发病．由于四时气候变化不同及人体差异,而有夹寒、夹热、夹暑、夹湿之别,以风寒、风热为多见．肺合皮毛,开窍于鼻,病邪侵袭致使卫气闭郁,肺气不宜,而恶寒发热,鼻塞、流涕．如急性期不及时治疗、鼻塞加重,鼻分泌物增多．西医可诊断为,单纯性鼻炎,肥厚性鼻炎,慢性鼻窦炎等．目前,对慢性鼻炎治疗效果不佳．我科采用贴耳针治疗本病,取得了较满意效果．１　对象和方法１．１　对象　１９９２～１９９８我科收治慢性鼻炎患者３５例．均作者简介：孙　静…     

Mechanisms of orientation of the pelvifemoral base during static loading of the lumbar spine in weight-lifters

Summary Under static loading during weight-lifting, the lumbosacral spine essentially exhibits horizontalisation of the base of the sacrum (superior plateau of S1). We have attempted to elicit the mechanism of this horizontalisation by means of radiographs. These do not demonstrate any movements of the sacroiliac joints or plasticity of the hip bones. However, a symmetrical rotation of the hip joints conditions a retroversion of the pelvic girdle which explains the horizontalisation of the upper sacral plateau. This fixation of the block of the pelvic girdle is under muscular control, so that this mechanism can be improved by appropriate training.

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Mécanismes d'orientation du socle pelvi-fémoral au cours de la mise en charge statique du rachis lombaire chez l'haltérophile

Resumé Sous charge statique, chez l'haltérophile, le rachis lombosacré présente essentiellement une horizontalisation du plateau supérieur de S1. Par radiographies, nous avons tenté de déterminer le mécanisme de cette horizontalisation. Les mouvements au niveau de la sacro-iliaque et la plasticité des os coxaux ne peuvent pas être mis en évidence sur les radiographies. Par contre, une rotation symétrique des coxo-fémorales détermine une rétroversion de la ceinture pelvienne permettant d'expliquer l'horizontalisation du plateau sacré. Ce verrouillage du bloc de la ceinture pelvienne est sous la dépendance des muscles et en conséquence, ce mécanisme peut être amélioré par un entraînement approprié.

     

Identification and characterization of a de novo partial trisomy 10p by comparative genomic hybridization (CGH)

We report the characterization of a de novo unbalanced chromosome rearrangement by comparative genomic hybridization (CGH) in a 15-day-old child with hypotonia and dysmorphia. We describe the combined use of CGH and fluorescence in situ hybridization (FISH) to identify the origin of the additional chromosomal material on the short arm of chromosome 6. Investigation with FISH revealed that the excess material was not derived from chromosome 6. Identification of unknown unbalanced aberrations that could not be identified by traditional cytogenetics procedures is possible by CGH analysis. Visual analysis of digital images from CGH-metaphase spreads revealed a predominantly green signal on the telomeric region of chromosome 10p. After quantitative digital ratio imaging of 10 CGH-metaphase spreads, a region of gain was found in the chromosome band 10p14-pter. The CGH finding was confirmed by FISH analysis, using a whole chromosome 10 paint probe. These results show the usefulness of CGH for a rapid characterization of de novo unbalanced translocation, unidentifiable by karyotype alone.     

Altered platelet calcium metabolism as an early predictor of increased peripheral vascular resistance and preeclampsia in urban black women

BACKGROUND. Although preeclampsia is an important and relatively common medical problem, its pathophysiology remains unresolved and the search for a biochemical marker that precedes the hemodynamic abnormalities of preeclampsia continues. We designed a study to investigate the hemodynamic changes that characterize preeclampsia and to evaluate the metabolism of platelet intracellular calcium as a possible predictor of the development of preeclampsia. METHODS. Hemodynamic measurements and spectrofluorometric determinations of the levels of intracellular calcium in platelets in the basal state and after stimulation with an agonist were performed in 48 nulliparous black women during each trimester of pregnancy. The data on the 14 women (29 percent) in whom preeclampsia developed were then compared with the data on the other 34, who served as normotensive controls. RESULTS. There was no significant difference between the two groups in the basal levels of intracellular calcium at any time. In contrast, the levels measured after arginine vasopressin was administered during the first trimester indicated an exaggerated response in the group with preeclampsia as compared with the control group (1494 +/- 388 [+/- SEM] percent vs. 545 +/- 55 percent of base line; P less than 0.0002), which was sustained through the second and third trimesters. All but three of the women with preeclampsia had responses higher than the highest response among the controls. Platelet intracellular calcium responses to arginine vasopressin during the first trimester were a sensitive predictor of the subsequent development of preeclampsia (P less than 0.00009). Although vascular resistance was similar in the two groups during the first trimester, it subsequently decreased in the control group (P less than 0.02) but not in the group with preeclampsia. CONCLUSIONS. Our findings indicate that preeclampsia is characterized by the absence of the normal pregnancy-related decrease in vascular resistance, which is preceded in most instances by an exaggerated response of platelet intracellular calcium to arginine vasopressin early in pregnancy. We therefore propose that an increase in the sensitivity of platelet calcium to arginine vasopressin can be used as an early predictor of subsequent preeclampsia.     

Whole-body lymphangioscintigraphy: preferred method for initial assessment of the peripheral lymphatic system

In 20 patients with congenital and acquired lymphedema in either upper or lower extremities and in four patients without extremity edema, human serum albumin labeled with technetium-99m was injected intradermally into a digital web space of the hand or foot. With a digital gamma camera that permitted a "sweep" of the torso, serial extremity and whole-body lymphagioscintigraphy (LAS) of the peripheral lymphatic system was performed. In 11 patients with acquired lymphedema, a well-defined obstructive pattern was seen, characterized by discrete peripheral lymphatic trunks, delayed or absent depiction of regional nodes, and delayed but extensive soft-tissue tracer extravasation. Five of nine patients with congenital lymphedema showed hypoplasia characterized by poorly defined lymphatic trunks, delayed depiction of regional nodes, and early and extensive extravasation of tracer. The other four patients showed aplasia, with absence of trunks, no depiction of nodes, and little or no tracer extravasation. LAS is technically simple to perform and requires no special training. Radiation exposure is minuscule, and the procedure is safe and without apparent side effects. For these reasons, whole-body LAS should be the preferred method for the initial assessment of congenital or acquired lymphedema.     

Profiling Patients’ Healthcare Needs to Support Integrated, Person-Centered Models for Long-Term Disease Management (Profile): Research Design

Background:This article presents the design of PROFILe, a study investigating which (bio)medical and non-(bio)medical patient characteristics should guide more tailored chronic care. Based on this insight, the project aims to develop and validate ‘patient profiles’ that can be used in practice to determine optimal treatment strategies for subgroups of chronically ill with similar healthcare needs and preferences.Methods/Design:PROFILe is a practice-based research comprising four phases. The project focuses on patients with type 2 diabetes. During the first study phase, patient profiles are drafted based on a systematic literature research, latent class growth modeling, and expert collaboration. In phase 2, the profiles are validated from a clinical, patient-related and statistical perspective. Phase 3 involves a discrete choice experiment to gain insight into the patient preferences that exist per profile. In phase 4, the results from all analyses are integrated and recommendations formulated on which patient characteristics should guide tailored chronic care.Discussion:PROFILe is an innovative study which uses a uniquely holistic approach to assess the healthcare needs and preferences of chronically ill. The patient profiles resulting from this project must be tested in practice to investigate the effects of tailored management on patient experience, population health and costs.