Incomplete antigenic cross-reactivity between platelets and megakaryocytes: relevance to ITP

Immune thrombocytopenias are usually associated with normal or increased numbers of megakaryocytes in the marrow. Therefore, the mechanism(s) responsible for the destruction of circulating platelets may not affect megakaryocytes in the same way. One of the possibilities which could account for the differential effect on the cells would be the development of antibodies to components of platelet membranes which are not exposed on the surface of all megakaryocytes. To investigate this possibility, a rabbit antiserum specific for mouse platelets was tested against fresh and cultured mouse megakaryocytes by indirect immunofluorescence. This antiserum cross-reacted with 46% of fresh murine megakaryocytes and 54% of cultured megakaryocytes. Phase- contrast microscopy revealed the reacting megakaryocytes to be fully granulated with irregular contours and in the process of releasing platelets. Nonreactive megakaryocytes demonstrated smooth contours and lacked morphological evidence of thrombocytopoiesis. Electron microscopy showed that only in megakaryocytes (MK) with an irregular contour had the demarcation membrane system (DMS) reached continuity with the plasma membrane. Ultrastructural analysis of megakaryocytes from patients with ITP showed approximately 25% to 50% of megakaryocytes without evidence of injury, whereas 50% to 75% had extensive damage. In undamaged cells, platelet territories had not yet reached the peripheral zone. The DMS of damaged megakaryocytes opened to the exterior elaborating platelets. The observations suggested that some platelet antibodies react only with megakaryocytes which have reached the stage of thrombocytopoiesis. Relevant target antigens may not be exposed on all megakaryocytes before cytoplasmic fragmentation occurs.     

Improved vessel dilator for percutaneous catheterization

Three commercial vessel dilators and a dilator of an improved design were tested during percutaneous catheterization in 16 mongrel dogs to evaluate arterial damage produced with their use. The results indicate that, although all dilators often produce arterial damage, the improved design produced much less damage. In addition, lesions were less severe overall. The dilator has been safely and successfully used in patients for percutaneous vessel catheterization for the past 30 years at the authors' institution.     

Increased height in diabetes mellitus corresponds to the predicted and the adult height

This study was conducted to analyse the effect of childhood-onset diabetes mellitus on adult height. The height at time of diagnosis of 35 children with insulin-dependent diabetes mellitus (IDDM) was compared with growth reference data. Predictions of the adult height were made at the time of diagnosis using the target height and the Tanner-Whitehouse II method. The adult height was compared with both the predicted values and the height of healthy adults. The height at time of diagnosis of the prepubertal children was increased compared with growth reference data, in contrast to pubertal children who had normal heights. Only the prepubertal boys were taller at time of diagnosis. The adult height of the prepubertal patients was taller than growth reference data. The mean adult height in all patients did not differ significantly from the predicted heights. In conclusion, the increased height at the start of IDDM in prepubertal children persists until adulthood.     

Effects of short-term hypoxia on platelet counts of mice

Recent studies have shown that long-term hypoxia causes decreased platelet counts in mice and short-term hypoxia increased platelet counts. In an attempt to explain the mechanism that increases platelet counts of mice after exposure to short-term hypoxia, we measured platelet counts, total circulating platelet counts (TCPC), total circulating platelet masses (TCPM), percentages of 35S incorporation, and platelet sizes. Platelet counts, as well as TCPC and TCPM of mice, increased after 1-3 days of hypoxia, but these values were decreased after 6-7 days of hypoxia. Although platelet counts were increased in hypoxic mice, the percentage 35S incorporation into platelets and platelet sizes did not show a concurrent increase. After 6 days of hypoxia, average platelet diameters began to increase as platelet counts decreased. Splenic release did not account for the increase in platelet counts of mice after short-term hypoxia. It seems possible, therefore, that megakaryocytes "shed" platelets into the circulation in response to hypoxia. The platelets that enter the circulation in response to short-term hypoxia are smaller and incorporate less 35S than platelets that are produced in response to acute thrombocytopenia.     

Prognostic significance of the Ki-67-associated proliferative antigen in aggressive non-Hodgkin's lymphomas: a prospective Southwest Oncology Group trial

The growth fraction of tumors from patients with non-Hodgkin's lymphomas (NHL) has been shown to correlate with survival in retrospective studies. The growth fraction can be evaluated using immunohistochemical techniques employing the Ki-67 monoclonal antibody (MoAb) that marks a nuclear protein present in cycling cells. The purpose of this study was to evaluate the clinical utility of the Ki-67 MoAb for predicting survival. Using a prospective trial design in a multi-institutional cooperative trials group, the proliferative index, clinical outcome, and statistical correlations were independently assessed for previously untreated patients with advanced stages of intermediate- and high-grade histologies of NHL treated on Southwest Oncology Group study (SWOG 8516, Intergroup 0067). The proportion of Ki- 67-positive cells was determined on snap-frozen thin tissue sections. A proliferative index of 80% or greater, as determined from prior retrospective studies, identified a group of patients (18%) who had a poor outcome. Overall survival was significantly reduced in these patients with a high Ki-67-associated proliferative index compared with those with a low proliferative index (P = .001). One-year survival estimates were 82% (low proliferative index) versus 18% (high proliferative index). A multivariate regression analysis incorporating commonly used clinical prognostic features confirmed the independent effect of proliferation on survival (relative risk estimate 5.9; 95% confidence interval, 2.2, 16.1). The Ki-67 MoAb identifies a group of patients with rapidly fatal NHL for whom currently available chemotherapy is inadequate.     

Dynamic exercise therapy in rheumatoid arthritis: a systematic review

The aim of this systematic review was to determine the effectiveness of dynamic exercise therapy in improving joint mobility, muscle strength, aerobic capacity and daily functioning in patients with rheumatoid arthritis (RA). In addition, possible unwanted effects such as an increase in pain, disease activity and radiological progression were studied. A computer-aided search of the MEDLINE, Embase and SCISEARCH databases was performed to identify controlled trials on the effect of exercise therapy. Randomized trials were selected on the effect of dynamic exercise therapy in RA patients with an exercise programme fulfilling the following criteria: (a) intensity level such that heart rates exceeded 60% of maximal heart rate during at least 20 min; (b) exercise frequency > or = 2 a week; and (c) duration of intervention > or = 6 weeks. Two blinded reviewers independently selected eligible studies, rated the methodological quality and extracted data. Six out of 30 identified controlled trials met the inclusion criteria. Four of the six included studies fulfilled > or = 7/10 methodological criteria. Because of heterogeneity in outcome measures, data could not be pooled. The results suggest that dynamic exercise therapy is effective in increasing aerobic capacity and muscle strength. No detrimental effects on disease activity and pain were observed. The effects of dynamic exercise therapy on functional ability and radiological progression are unclear. It is concluded that dynamic exercise therapy has a positive effect on physical capacity. Research on the long-term effect of dynamic exercise therapy on radiological progression and functional ability is needed.      

胰岛ε细胞的研究进展

胰腺由外分泌组织和内分泌组织2个部分所组成,两者在机体能量平衡和营养代谢调节中发挥重要的作用．胰岛是胰腺组织中重要的内分泌功能单位,胰岛的发育和分化过程涉及一个复杂而精细的分子调控网络体系,其中包括许多转录因子的参与．经典的胰岛内分泌细胞包括α细胞、β细胞、δ细胞及PP细胞,分别产生胰升糖素、胰岛素、生长抑素及胰多肽(PP),各种胰岛细胞之间的相互调节在维持血糖稳态中具有重要的意义．表达ghrelin 的ε细胞是一种新近发现和命名的胰岛细胞类型．现着重对胰岛ε细胞的发现过程、形态学特点及生物学作用进行介绍．     

Treatment of cluster headache in pregnancy and lactation

Cluster headache is a rare disorder in women, but has a serious impact on the affected woman's life, especially on family planning. Women with cluster headache who are pregnant need special support, including the expertise of an experienced headache centre, an experienced gynaecologist and possibly a teratology information centre. The patient should be seen through all stages of the pregnancy. A detailed briefing about the risks and safety of various treatment options is mandatory. In general, both the number of medications and the dosage should be kept as low as possible. Preferred treatments include oxygen, subcutaneous or intranasal sumatriptan for acute pain and verapamil and prednisone/prednisolone as preventatives. If there is a compelling reason to treat the patient with another preventative, gabapentin is the drug of choice. While breastfeeding, oxygen, sumatriptan and lidocaine for acute pain and prednisone/prednisolone, verapamil, and lithium as preventatives are the drugs of choice. As the individual pharmacokinetics differ substantially, adverse drug effects should be considered if unexplained symptoms occur in the newborn.     

Patient satisfaction with doctor–patient interaction in a radiotherapy centre during the severe acute respiratory syndrome outbreak

An outpatient radiotherapy department assessed how precautions implemented during the severe acute respiratory syndrome (SARS) outbreak affected patient satisfaction with doctor–patient interaction and explored variables potentially influencing satisfaction. The information obtained would help prepare us for future infectious disease outbreaks. Outpatients seen during the outbreak completed a validated questionnaire assessing satisfaction with doctor–patient interaction. Additional items assessed included patients’ perception of SARS measures and patient demographics. Of 149 patients, 97% had heard of SARS, 92% believed SARS precautions necessary, and 54% believed contracting SARS was possible despite the precautions. Patients were satisfied with doctors wearing masks (97%), temperature checks (97%), and patients wearing masks (96%). Despite the high satisfaction levels with SARS precautions, 24% believed it had adversely affected doctor–patient interaction. With regards to doctor–patient interaction, 94% of patients were satisfied. Patients were most satisfied with the ‘information exchange’ domain (mean score 3.23 out of 4) compared to other domains (P < 0.0001, 100.00% confidence) and were less satisfied with the ‘empathy’ domain compared to other domains (P < 0.0001, 100.00% confidence). Patients were most satisfied with understanding their treatment plan (100%), doctor being honest (97%) and being understood (96%). Patients were least satisfied with information about caring for their illness (61%), that the visit could be better (59%), and the doctor showing more interest (58%). On multivariate analysis, patients who were less satisfied with SARS measures were significantly less satisfied with doctor–patient interaction (P = 0.0001). Dissatisfaction with SARS measures was associated with significant dissatisfaction for questions in all domains. Older age and non‐breast cancer patients were also less satisfied with doctor–patient interaction. Most (94%) of patients were satisfied with doctor–patient interaction, despite implementation of infectious disease prevention measures. However, patients who were dissatisfied with the SARS precautions had poorer satisfaction. In particular, physician empathy appeared to be most adversely affected. The results have relevance to any radiotherapy department preparing contingency plans in the event of infectious disease outbreaks.