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101.
Phase I trial of interleukin-2 after unmodified HLA-matched sibling bone marrow transplantation for children with acute leukemia 总被引:1,自引:1,他引:1
Robinson N; Sanders JE; Benyunes MC; Beach K; Lindgren C; Thompson JA; Appelbaum FR; Fefer A 《Blood》1996,87(4):1249-1254
Allogeneic bone marrow transplantation (BMT) for advanced acute leukemia is associated with a high risk of relapse. It is postulated that interleukin-2 (IL-2) administered after BMT might induce or amplify a graft-versus-leukemia effect and thereby reduce the relapse rate. To identify an IL-2 regimen for testing this hypothesis, a phase I trial of IL-2 (Roche) was performed in children in complete remission (CR) without active graft-versus-host disease (GVHD) off immunosuppressive agents after unmodified allogeneic matched-sibling BMT for acute leukemia beyond first remission. Beginning a median of 68 days after BMT, 17 patients received escalating doses of induction IL-2 (0.9, 3.0, or 6.0 x 10(6) IU/m2/d representing levels I, II, and III) for 5 days by continuous intravenous infusion (CIV). After 6 days of rest, they received maintenance IL-2 (0.9 x 10(6) IU/m2/d) for 10 days by CIV infusion. Levels I and II were well-tolerated, but, of 6 patients at level III, 1 developed pulmonary infiltrates, 1 developed hypotension (both resolved), and 1 died of bacterial sepsis and acute respiratory distress syndrome. Grade II acute GVHD developed in 1 patient at level I and 1 at level III. The maximum tolerated dose of induction IL-2 was level II. IL-2 induced lymphocytosis, with an increase in CD56+ and CD8+ cells. Ten patients remain in CR at 5+ to 67+ months. Thus, a regimen of IL-2 has been identified that did not induce a high incidence of acute GVHD when administered to children after unmodified allogeneic BMT. Its clinical activity will be assessed in a phase II trial. 相似文献
102.
Christopher Lopata Christin A. McDonald Marcus L. Thomeer James P. Donnelly Allyson K. Jordan Jonathan D. Rodgers 《Journal of developmental and physical disabilities》2018,30(4):439-454
This study examined the feasibility and preliminary outcomes of a comprehensive summer psychosocial treatment (summerMAXyc) for high-functioning young children, ages 4–6 years, with ASD (HFASD). The 5-week treatment, conducted 5 days per week, 6 h per day, included skills instruction and therapeutic activities targeting social/social-communication skills, facial-emotion recognition, and interest expansion. A behavioral system was implemented to increase skills acquisition and maintenance and reduce ASD symptoms and problem behaviors. Feasibility was supported in high levels of treatment fidelity and child, parent, and staff clinician satisfaction. Significant post-treatment improvements were found for 9 of 10 outcome measures including parent and staff clinician ratings of targeted social/social-communication skills, ASD symptoms, and broader adaptive social and communication skills, and staff clinician ratings of daily living skills. Results suggested that summerMAXyc was feasible and may yield positive outcomes for 4–6 year olds with HFASD. 相似文献
103.
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105.
The role of ambulatory blood pressure (ABP) monitoring in the assessment of mild/borderline hypertension (BHT) is unclear. The aim of this study was to test the hypothesis that measurement of ABP in borderline hypertensives differentiates patients with true mild hypertension from those with isolated clinic hypertension (raised office BP but normal ABP) and that a raised ABP identifies a subgroup who are more likely to progress to and require treatment over 1 year. Consecutive untreated patients with BHT (n = 127, 44 +/- 13 years, 45% male) were divided into two groups according to awake ABP: Group 1 (normal ABP < or = 136/86, n = 48), and Group 2 (abnormal ABP > 136/86, n = 79). Left ventricular mass index (LVMI) was greater (116 +/- 30 vs 101 +/- 25 g/m2, p < 0.01) and the proportion of patients with an increased LVMI was significantly higher (34% vs 17%, p = 0.05) in Group 2. During 1 year of follow-up, significantly more patients in Group 2 (34%) required antihypertensive treatment compared with Group 1 (8%, p = 0.01). ABP monitoring usefully discriminates between patients with true BHT and those with isolated clinic hypertension. An elevated awake ABP on initial assessment is associated with a higher LVMI and a greater likelihood of progression to moderate hypertension requiring pharmacological treatment. 相似文献
106.
Hypoglossal motoneuron responses to pulmonary and superior laryngeal afferent inputs 总被引:6,自引:0,他引:6
In decerebrate, paralyzed cats ventilated with a cycle-triggered pump, the inspiratory discharges of the hypoglossal (whole nerve or single fibers), phrenic, and recurrent laryngeal nerves were compared, and the effects of pulmonary and superior laryngeal afferent inputs were observed. During lung inflations in phase with neural inspiration, hypoglossal and recurrent laryngeal activities differed from phrenic with respect to (a) burst onset times: both preceded the phrenic; (b) overall pattern: phrenic, augmenting; hypoglossal, decrementing; recurrent laryngeal, plateau-like. When inflation was withheld, the phrenic pattern was not markedly changed, but both hypoglossal and recurrent laryngeal became augmenting; the marked increase of hypoglossal activity (both whole nerve and single fiber) indicated strong inhibition by lung afferents. Superior laryngeal electrical stimulation evoked excitation of the contralateral phrenic (latency 4.1 msec) and the ipsilateral whole hypoglossal (latency 5.3 msec), followed by bilateral inhibitions (durations 20-30 msec); most hypoglossal fibers showed only inhibition. We conclude that, although both hypoglossal and phrenic outputs are driven by the inspiratory pattern generator(s), their promotor systems differ with respect to influences from central and peripheral inputs. 相似文献
107.
In the standard treatment of patients with haematological malignancy, immunosuppressive therapy produces prolonged periods of neutropenia and mucositis, which increase the risk of systemic fungal infection. In allogeneic bone marrow transplantation, this risk extends well beyond the period of neutropenia when graft-versus-host disease, and its treatment, result in prolonged lymphocytopenia. Various agents are used for antifungal prophylaxis and treatment but all have limitations: amphotericin B is restricted by the need for intravenous infusion and the occurrence of adverse events, fluconazole by its narrow spectrum of activity and the emergence of fluconazole-resistant fungi and itraconazole capsules by erratic absorption. Oral administration of antifungals has clear advantages in prophylaxis and an important current strategy is to maximize the extent and reliability of the oral bioavailability of antifungal agents. Mucositis is the main obstacle for success of strategies based on oral delivery. In this review, the ability of these new oral formulations to deliver sufficient antifungal prophylaxis is evaluated. 相似文献
108.
SG Lindquist M Duno M Batbayli A Puschmann H Braendgaard S Mardosiene K Svenstrup LH Pinborg K Vestergaard LE Hjermind J Stokholm BB Andersen P Johannsen JE Nielsen 《Clinical genetics》2013,83(3):279-283
Recently, a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 was reported as the cause of chromosome 9p21‐linked frontotemporal dementia‐amyotrophic lateral sclerosis (FTD‐ALS). We here report the prevalence of the expansion in a hospital‐based cohort and associated clinical features indicating a wider clinical spectrum of C9ORF72 disease than previously described. We studied 280 patients previously screened for mutations in genes involved in early onset autosomal dominant inherited dementia disorders. A repeat‐primed polymerase chain reaction amplification assay was used to identify pathogenic GGGGCC expansions. As a potential modifier, confirmed cases were further investigated for abnormal CAG expansions in ATXN2. A pathogenic GGGGCC expansion was identified in a total of 14 probands. Three of these presented with atypical clinical features and were previously diagnosed with clinical olivopontocerebellar degeneration (OPCD), atypical Parkinsonian syndrome (APS) and a corticobasal syndrome (CBS). Further, the pathogenic expansion was identified in six FTD patients, four patients with FTD‐ALS and one ALS patient. All confirmed cases had normal ATXN2 repeat sizes. Our study widens the clinical spectrum of C9ORF72related disease and confirms the hexanucleotide expansion as a prevalent cause of FTD‐ALS disorders. There was no indication of a modifying effect of the ATXN2 gene. 相似文献
109.
110.
Use of anorectal manometry during rectal infusion of saline to investigate sphincter function in incontinent patients 总被引:18,自引:0,他引:18
N W Read W G Haynes D C Bartolo J Hall M G Read T C Donnelly A G Johnson 《Gastroenterology》1983,85(1):105-113
Anal and rectal pressures and external sphincter electromyogram were recorded continuously during rectal infusion of 1.5 L saline in 18 normal subjects and 37 patients who complained of diarrhea and fecal incontinence. All subjects exhibited a pattern of regular fluctuations in anorectal pressure and electromyogram. All except 1 of the normal subjects were able to retain 1500 ml saline without leakage, and their pressure record comprised simultaneous rectal contractions, internal sphincter relaxations, and external sphincter contractions. None of the incontinent patients were able to retain 1500 ml saline without leakages, and leakages always coincided with the peaks of rectal pressure. Two manometric patterns were observed. Fifty-nine percent of incontinent patients exhibited a pattern of contractions of similar profile occurring throughout the anorectum. This finding was associated with low basal sphincter pressures, an easily inhibited anal sphincter tone, an obtuse anorectal angle, and a funnel-shaped configuration to the anal canal. These results suggested that, in this group, the internal sphincter was weak and easily inhibited so that the whole anorectum behaved as one fluid-filled compartment recording contractions of the external sphincter. The remaining 41% of incontinent patients exhibited a normal pattern of anorectal pressure fluctuations and had normal maximum basal pressures, although maximum squeeze pressures, rectoanal inhibitory reflex, and anorectal angles were abnormal. Peak rectal pressures were abnormally high in this group during saline infusion, suggesting that abnormally strong rectal contractions may play a role in the incontinence in this group. 相似文献