The investigation of karyotypic instability in the high-hyperdiploidy subgroup of acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) of childhood has been cytogenetically well characterized, and approximately 25% of cases will have a high-hyperdiploid (51-68) chromosome complement. In a 5 year period a consecutive series of 152 presentation ALL's were karyotyped. In all cases a result was obtained and 138 (91%) had a detectable abnormal clone of which 44 (29%) were high-hyperdiploid. Within the high-hyperdiploidy group karyotypic cell to cell variation was observed in many cases. To provide further evidence of this phenomenon a dual-color fluorescence in-situ hybridization (FISH) experiment was performed on stored fixed suspension from 14 ALL's with such a karyotype. In each case 4-6 probes were investigated, employing probes to centromeres of chromosomes X, 4, 6, 8, and 10 and a locus specific probe to chromosome 21q22. It was found that the FISH produced results that were generally in good agreement with the G-banding findings and supported the notion of karyotypic cell to cell variation. FISH further showed that most of cases would have two extra copies of chromosome 21 in the majority of leukemic cells and a single extra copy in the minority. A further finding was that fewer cells contained extra copies of chromosomes 6, 8 and 10 than was expected based on the comparison of the signal number of the other probes investigated. In contrast chromosomes X, 4, and 21 seldom displayed this feature. We have demonstrated that karyotypic instability as defined by karyotypic cell to cell variation is a feature of the high-hyperdiploid subgroup in childhood ALL. It is questioned whether the underlying defect resulting in the observed karyotypic instability of this subgroup is one of the primary causative events in the formation of the leukemia.     

二甲双胍和瑞格列奈对非肥胖的2型糖尿病患者非血糖性心血管危险标志的影响比较

在2型糖尿病患者中，反映炎症和内皮功能障碍的生物标志已经与心血管疾病和代谢调节联系起来。二甲双胍和促胰岛素分泌剂被证明有相同的抗高血糖作用。此研究比较了二甲双胍和促胰岛素分泌剂瑞格列奈在非肥胖的2型糖尿病患者的心血管疾病生物标志上的效能。     

The Viladot implant in flatfooted children

In 1991, Viladot described an implant for the treatment of painless flatfeet in children. This was inserted through a double approach to allow the talus to function while limiting its ability to slide off the calcaneus. The wineglass shaped prosthesis was inserted into the sinus tarsi with a tibialis posterior advancement and soft tissue correction to allow the foot to adopt a neutral position. This is in keeping with other procedures described for the correction of flatfoot. Viladot reported excellent results in 234 feet operated on in such a manner using clinical, radiological and photopodographic parameters. In Sheffield, over three years, 22 implants were inserted for similar painless flatfeet in children. The results were assessed using clinical, radiological and pedobarographic parameters. Viladot was able to demonstrate an improvement in all cases, clinically, radiologically and photopodographically with little or no discomfort and a return to preoperative levels of activity including sport. We found that in all cases, postoperative pain was a major feature which limited activity in all but 2 feet and which reduced the ability to take part in sport and other preoperative pastimes. Unlike Viladot, we were unable to demonstrate consistent improvements radiologically. Pedobarographically, the loading of the first metatarsal head remained unchanged and the centre of pressure was corrected in only 14%.     

Peripheral cytokine responses to Trichuris muris reflect those occurring locally at the site of infection

The study of human cellular immune responses to parasite infection under field conditions is very complex. Often, the only practical site from which to sample the cellular responses is the peripheral blood. Sampling peripheral blood lymphocytes (PBL) relies on the assumption that these peripheral responses accurately reflect the immune responses acting locally at the site of infection. This is a particularly important point for the human intestinal helminth Trichuris trichiura, which solely inhabits the cecum and large intestine and so will stimulate a localized immune response. Using the well-defined model of T. trichiura, T. muris in the mouse, we have demonstrated that the dominant cytokine responses of the mesenteric lymph nodes (MLN) can be detected by sampling PBL. Resistant mice which mount a type 2 cytokine response in their MLN had PBL producing interleukin-4 (IL-4), IL-5, and IL-9, with negligible levels of gamma interferon (IFN-gamma). Conversely, susceptible mice which mount a type 1 cytokine response in their MLN had PBL producing IFN-gamma and negligible levels of type 2 cytokines. We have also shown that the PBL are capable of mounting a functional immune response against T. muris. PBL from immune mice were capable of transferring immunity to T. muris-infected severe combined immunodeficient (C.B-17 scid/scid) mice. Sampling PBL responses is therefore a viable option for monitoring human intestinal immune responses during T. trichiura infection in the field.     

Psychological response to growth hormone treatment in short normal children.

This study provides a controlled assessment of the psychological (and physical) effects of growth hormone treatment. Fifteen short ''normal'' children (height SD score < -2) have been treated with growth hormone since the age of 7/8 years. They, together with untreated short controls and average controls (10th-90th centiles), were assessed at recruitment, after three years, and after five years. Only the treated group showed a significant height increase (SD score -2.44 to -1.21 over five years). No significant differences were found at recruitment, three years, or five years in IQ, attainment, behaviour, or self esteem. Also at five years, there were no significant differences in locus of control, self perception, or parental perceptions of competence. Both short groups displayed less satisfaction with their height than the controls (p < 0.01), though all groups were optimistic of being tall adults. The treated children were no more unrealistic over final height than the untreated children. To date, no psychological benefits of treatment have been demonstrated; but nor have there been any discernible ill effects for either the treated or the untreated children.     

Shwachman-Diamond syndrome: early bone marrow transplantation in a high risk patient and new clues to pathogenesis

Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder characterised by exocrine pancreas insufficiency, metaphyseal dysostosis and bone marrow dysfunction. Recurrent severe bacterial infections and susceptibility to leukaemia are the major causes of morbidity and mortality occurring preferentially in patients with pancytopenia and features of myelodysplasia. Here we report a patient with SDS leading to recurrent bacterial infections and a deteriorating condition since early infancy. Extensive investigations disclosed severe pancytopenia, myelodysplasia and a clonal cytogenetic abnormality, inv(14)(q11q32), as risk factors of leukaemic transformation. He therefore underwent allogeneic geno-identical bone marrow transplantation which resulted in correction of all haematological and immunological abnormalities within an 18-month follow up period. Conclusion Bone marrow transplantation may be considered early as a valuable treatment option especially in high risk Schwachman-Diamond syndrome patients anticipating malignant transformation, life-threatening severe infections or further organ damage. Received: 19 February 1999 / Accepted: 22 June 1999     

Rehabilitation-specific communication skills training: improving the physician-patient relationship.

OBJECTIVE: Evaluate the effectiveness of a rehabilitation-specific communication skills training program for physicians. DESIGN: Three groups of rehabilitation patients were interviewed 3 mo after discharge, one group before and two groups after implementation of a communication skills training program. The setting was a free-standing rehabilitation hospital with a residency training program. A total of 245 patients who had been discharged from the rehabilitation hospital participated in the study. A communication skills training program that was designed specifically for physicians and patients in the rehabilitation setting was used as an intervention. Patients' perceptions of the extent to which physicians accomplished 18 communication tasks highlighted by the training program were gauged in a structured telephone interview. RESULTS: Participants interviewed after the training program was implemented more strongly agreed that their physicians accomplished the communication tasks assessed than did patients interviewed before the training program began. On 14 of 18 items, the differences were statistically significant (P < 0.05). CONCLUSION: Specialty-specific communication training can improve physician communication skills.