Graves′病患者经~(131)碘治疗后循环活性T细胞亚群的动态观察

本文应用直接、间接双色免疫荧光染色,流体细胞测定仪技术,观察了经~(131)碘治疗的23例Graves′病患者的循环活性T细胞亚群的动态变化。~(131)碘治疗后的第一个月至第三个月,HLA-DR、Ta_1和UCHL_1活性T细胞亚群数目明显增加,以Vicia-villosa为标志的抗抑制细胞亚群较治疗前明显增加。实验结果提示:Graves′病患者经~(131)碘治疗后的抗甲状腺自身抗体浓度增加可能是由于T细胞的激活和抗抑制细胞亚群增加的共同结果。     

Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graft-versus-leukemia responses from graft-versus-host disease

Infusions of large numbers (> 10(8)/kg) of donor leukocytes can induce remissions in patients with chronic myeloid leukemia (CML) who relapse after marrow transplantation. We wanted to determine if substantially lower numbers of donor leukocytes could induce remissions and, if so, whether this would reduce the 90% incidence of graft-versus-host disease (GVHD) associated with this therapy. Twenty-two patients with relapsed CML were studied: 2 in molecular relapse, 6 in cytogenetic relapse, 10 in chronic phase, and 4 in accelerated phase. Each patient received escalating doses of donor leukocytes at 4- to 33-week intervals. Leukocyte doses were calculated as T cells per kilogram of recipient weight. There were 8 dose levels between 1 x 10(5) and 5 x 10(8). Lineage-specific chimerism and residual leukemia detection were assessed using sensitive polymerase chain reaction (PCR) methodologies. Nineteen of the 22 patients achieved remission. Remissions were achieved at the following T-cell doses: 1 x 10(7) (n = 8), 5 x 10(7) (n = 4), 1 x 10(8) (n = 3), and 5 x 10(8) (n = 4). To date, 15 of the 17 evaluable patients have become BCR-ABL negative by PCR. The incidence of GVHD was correlated with the dose of T cells administered. Only 1 of the 8 patients who achieved remission at a T-cell dose of 1 x 10(7)/kg developed GVHD, whereas this complication developed in 8 of the 11 responders who received a T-cell dose of > or = 5 x 10(7)/kg. Three patients died in remission, 1 secondary to marrow aplasia, 1 of respiratory failure and 1 of complications of chronic GVHD. Sixteen patients who were mixed T-cell chimeras before treatment became full donor T-cell chimeras at the time of remission. Donor leukocytes with a T-cell content as low as 1 x 10(7)/kg can result in complete donor chimerism together with a potent graft-versus-leukemia (GVL) effect. The dose of donor leukocytes or T cells used may be important in determining both the GVL response and the incidence of GVHD. In many patients, this potent GVL effect can occur in the absence of clinical GVHD.     

Fractionated total-body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 94 patients with chronic myelogenous leukemia in chronic phase

Ninety-four consecutive patients with chronic myelogenous leukemia in first clinical chronic phase, median age of 34.0 years (range, 6.8 to 52.4 years), with a histocompatible sibling donor, were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation (BMT). The median time from diagnosis to BMT was 7.0 months (range, 2.3 to 72.0 months). Sixty patients were treated before BMT with hydroxyurea alone, four patients with busulfan alone, one patient with interferon alone, and the other 29 patients were treated with various combinations of these drugs. Cumulative probabilities of overall survival, event- free survival, and relapse at 5 years were 73%, 64%, and 14%, respectively. The median follow-up time for surviving patients was 38 months, ranging from 12 to 88 months. By stepwise Cox regression analysis, significant prognostic variables were age at transplant, acute graft-versus-host disease > or = grade II, cytomegalovirus- associated interstitial pneumonitis, and years from diagnosis to BMT.     

Hypocalcaemia in severe meningococcal infections

AIM: To determine the incidence of hypocalcaemia in critically ill children with meningococcal disease. METHODS: In a prospective cohort study, 70 of 80 patients admitted consecutively with a clinical diagnosis of meningococcal disease to intensive care had measurements of total and ionised calcium on admission. Parathormone and calcitonin were measured in a proportion of the children. RESULTS: Total and ionised calcium concentrations were low in 70% of the children. There was a weak relation of calcium concentration to the volume of blood derived colloid which had been given, but a good relation to disease severity, where sicker children had lower calcium concentrations. Although the parathormone concentration was higher in children with lower calcium concentrations, some children had low ionised calcium concentrations, without an increase of parathormone concentration. Serum calcitonin concentration was not related to calcium concentrations. CONCLUSION: Hypocalcaemia is common in meningococcal disease.     

Identification of malaria hot spots for focused intervention in tribal state of India: a GIS based approach

Background  

In India, presently malaria shows a declining trend whereas Plasmodium falciparum (Pf) cases show an up trend. In central India, specifically, Madhya Pradesh (M.P.) a forested and tribal area, control of malaria is logistically difficult and outbreaks are frequently recorded, reasons for this being inadequate surveillance, poor reporting, a time lag in reporting to decision makers and a lack of geo referenced information to pin point the trouble spots for a timely preventive action.     

Musculoskeletal modelling in determining the effect of botulinum toxin on the hamstrings of patients with crouch gait

This study aimed to determine the effect of hamstring botulinum toxin A (Btx-A) injection in 10 children with crouch gait in terms of changes in muscle length and lower-limb kinematics. Before Btx-A injection limb kinematics were recorded. Maximum hamstring lengths and excursions were calculated by computer modelling of the lower limb. Data were compared with the averaged hamstring lengths of 10 control children. Hamstrings were denned as short if their length was shorter than the average maximum length minus one standard deviation. Gait analysis was repeated 2 weeks after isolated hamstring Btx-A injection. Pre- and postinjection kinematic data and muscle lengths were then compared. Four of 18 injected limbs in three subjects had short medial hamstring before injection, none of the subjects had short lateral hamstrings. Muscle excursion was significantly reduced in the short and adequate maximum muscle length groups. A significant increase in the semimembranosus and semitendinosus length in all of the injected limbs was noted. Only in the short muscle group was a significant increase in muscle excursion observed. Knee extension improved by 13° in the adequate muscle length group and by 15.6° in the short muscle length group. Pelvic tilt and hip flexion increased in both groups non-significantly. Average walking speed postinjection increased from 0.60 ms^-1 to 0.71 ms^-1. Short hamstrings are over-diagnosed in crouch gait. Hamstring Btx-A injection in patients with crouch gait produces significant, repeatable muscle lengthening and improved ambulatory function.     

NOD mice are resistant to depletion of thymic cells caused by acute stress or infection.

NOD mice spontaneously develop autoimmune diabetes; disease onset in females of our colony of NOD mice usually takes place around the 4th month of age. Diabetes of NOD mice can be modulated by different stress protocols, even though these animals were shown to be resistant to the effects of glucocorticoids on their lymphocytes. We have recently found that the early host inflammatory response to mycobacteria can be strongly modified by stress, the autoimmunity-prone NOD and NZB/W mice being particularly affected. These mice show reduced numbers of granulocytes in the inflammatory cavity after exposure to stress. Mycobacterium avium is an opportunistic agent that is responsible for disseminated infections seen in AIDS patients. Here, we investigated whether the early immune response to M. avium was altered by stress in NOD mice and we compared the stress response of these mice with a non-autoimmune strain, BALB/c mice. The effects of stress on infected BALB/c mice, which like AIDS patients are susceptible to M. avium infection, offers experimental evidence that M. avium infection, if coupled with stress of the host, may accelerate loss of T helper cells. In contrast, in NOD mice, stress or infection significantly increased the number of cells of the thymuses of the animals. Data obtained with NOD mice support the previously reported resistance of NOD mice lymphocytes to glucocorticoids and suggest that there are two distinct signalling pathways involved in the response of NOD lymphocytes to these stress hormones: one leading to apoptosis and the other mediating glucocorticoid inhibition of activation-induced cell death.