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.     

Giant lumbar spinal schwannoma: a case report and literature review

We report a case of a 40-year-old female patient admitted to the hospital due to lumbar pain that spread to both legs and was associated with weakness of the lower extremities. Magnetic resonance imaging revealed an intradural - extramedullary tumor at the level of the T12 - L2 vertebra. The lesion was over 7 cm in greatest diameter and compressed the conus medullaris. The patient underwent surgery to remove the entire tumor. Postoperative pathology confirmed the diagnosis of schwannoma. The symptoms resolved almost completely without significant complications.     

Application of machine learning in screening for congenital heart diseases using fetal echocardiography

The International Journal of Cardiovascular Imaging - There is a growing body of literature supporting the utilization of machine learning (ML) to improve diagnosis and prognosis tools of...     

Face representation in the human secondary somatosensory cortex.

OBJECTIVE: To investigate the somatotopic organization of the facial skin area in the secondary somatosensory cortex (SII) in humans. METHODS: Somatosensory evoked magnetic fields following air-puff stimulation of 5 body sites, the foot, the lip and 3 points of the facial skin (forehead, cheek and mandibular angle point), were recorded. We focused on activities in SII following stimulation of these 5 sites and compared dipole locations among them. RESULTS: There was a clear somatotopic organization in SII with lip in the most lateral area, foot in the most medial area and face in an intermediate area close to the lip area. However, there was no significant difference of dipole localization in SII among the 3 areas of facial skin, similar to the overlapped somatotopic organization of facial skin areas in the primary somatosensory cortex in our previous study. CONCLUSIONS: The facial skin areas are considered to occupy a small area in SII with insufficient spatial separation to differentiate each area of facial skin even using magnetoencephalography which has a high spatial resolution. SIGNIFICANCE: This is the first systematic study of the activated regions in SII following stimulation of the facial skin.     

Manipulating the mandibular distraction site at different stages of consolidation.

PURPOSE: The purpose of this study was to define optimal timing and conditions for correcting an open bite side effect by manipulating the distraction site with orthodontic springs after mandibular distraction. MATERIALS AND METHODS: At 0, 1, 2, 3, and 8 weeks postdistraction, interarch springs were attached for 2 weeks to close distraction-produced open bites in 45 rabbits. Distractors were removed in half of the animals receiving spring treatment. Segment position was recorded by weekly direct measurements and radiographs. Tissue samples were collected at the end of spring application for microcomputerized tomography analysis and measurements of lateral symmetry. RESULTS: Orthodontic springs closed the open bite with or without distractors in place immediately after distraction and partially corrected the bite at later stages of bone consolidation. Distractor removal produced more rapid bite closure but also introduced lateral buckling of the distraction site during early consolidation. The lateral buckling was not observed if springs were applied after 2 weeks of consolidation. The amount of bite correction with orthodontic springs correlated with mineralization of the distraction site. CONCLUSION: During the consolidation period, a distraction site can be callus manipulated with orthodontic springs to correct an open bite. The amount of correction depended on when springs were placed and whether distractors were removed at the time of spring application.     

ParaSight-F test to diagnose malaria in hypo-endemic and epidemic prone regions of Vietnam

The antigen capture Para Sight-F test was evaluated during a drug sensitivity survey in a hypoendemic region of northern Vietnam. When only asexual blood forms of P. falciparum were considered, sensitivity of ParaSight-F was 100%, specificity 88% (95% CI 95–80%), positive predictive value 68% (95% CI 85–50%) and negative predictive value 100%. ParaSight-F proved very convenient for rapid screening and selection of patients to enrol in a drug sensitivity study. In northern Vietnam, the introduction of the test as a routine diagnostic tool is not justified, considering its high cost, the necessity to carry out the treatment of presumptive Plasmodium vivax cases and the persistence of positive reactions following treatment. However, the test will be a valuable tool in remote areas in emergency situations, where rapid confirmation of a P. falciparum outbreak is required.     

ANGIOTENSIN CONVERTING ENZYME AND SUBSTANCE P CHANGES IN BLISTER FLUID FOLLOWING AFFERENT NERVE STIMULATION IN THE RAT

We have examined the effect of electrical nerve stimulation on substance P and angiotensin converting enzyme activity in the interstitial fluid of rat skin using a blister model. Following sciatic nerve stimulation, blister fluid immunoreactive substance P (fmol/ml) was increased from 118 (unstimulated side, s.e.m. = 13, n = 15) to 197 (stimulated side, s.e.m. = 26, n = 15, P less than 0.0125, paired t-test, 14 d.f.). Angiotensin converting enzyme (ACE) activity (nmol HL/ml per h) was reduced in blister fluid from 26.5 (unstimulated side, s.e.m. = 2.4, n = 12) to 22.4 (stimulated side, s.e.m. = 1.4, P less than 0.05, paired t-test, 11 d.f.). Electrical stimulation of afferent nerves inhibits angiotensin converting enzyme activity in vivo. This may contribute to the process of neurogenic inflammation.