Adoptive transfer of minor histocompatibility antigen-specific T lymphocytes eradicates leukemia cells without causing graft-versus-host disease.

Adoptive transfer of T cells reactive to minor histocompatibility antigens has the unmatched ability to eradicate malignant hematopoietic cells. Unfortunately, its use is hampered by the associated graft-versus-host disease. The critical issue of a possible dissociation of the antileukemic effect and graft-versus-host disease by targeting specific minor histocompatibility antigens remains unresolved because of the unknown nature and number of minor histocompatibility antigens necessary or sufficient to elicit anti-leukemic activity and graft-versus-host disease. We found that injection of T lymphocytes primed against a single major histocompatibility complex class I-restricted immunodominant minor histocompatibility antigen (B6dom1) caused no graft-versus-host disease but produced a curative anti-leukemic response. Avoidance of graft-versus-host disease required that no other host-reactive T cells be co-injected with T cells primed with B6dom1. Here we show that effective and non-toxic immunotherapy of hematologic malignancies can be achieved by targeting a single immunodominant minor histocompatibility antigen.

Expression of genes related to activity of oxaliplatin and 5-fluorouracil in endoscopic biopsies of primary esophageal cancer in patients receiving oxaliplatin, 5-flourouracil and radiation: characterization and exploratory analysis with survival.

With a goal of identifying relations between gene expression and response (mucosal or pathological) or survival in esophageal cancer patients (stages II to IV) receiving oxaliplatin, 5-fluorouracil (5FU) and radiation, we measured in endoscopic primary tumor biopsies from 38 patients, the expression of seven genes (gammaGCS, gammaGT, MRP-2, ERCC-1, XPA, TS and DPD) prior to treatment, 1 week following oxaliplatin alone and at the end of the combined radio-chemotherapy cycle using real time QRT-PCR. A higher pretreatment level of XPA was related to shorter survival with a hazard ratio of 2.43 (90% confidence interval 1.09 to 5.43) using Cox regression modeling. However, multivariate analysis with a Cox model indicated low expression of XPA or TS and combined stages II and III had a higher probability of survival (for XPA: hazard ratio 3.0 and 90% C.I. of 1.3 to 6.9, with adjustment for stage included; for TS: hazard ratio is 1.98 with 90% C.I. of 0.94 to 4.20. The expression of TS, gammaGCS, ERCC-1 and MRP-2 declined from D 1 to the end of the cycle (p<0.05, sign test). A validation and further understanding of the findings need to be carried out in a larger study with a more homogeneous population of patients.

Nodal basin recurrence following lymph node dissection for melanoma: implications for adjuvant radiotherapy.

PURPOSE: To analyze patterns of failure in malignant melanoma patients with lymph node involvement who underwent complete lymph node dissection (LND) of the nodal basin. To determine prognostic factors predictive of local recurrence in the lymph node basin in order to select patients who may benefit from adjuvant radiotherapy. METHODS AND MATERIALS: A retrospective analysis of 338 patients undergoing complete LND for melanoma between 1970 and 1996 who had pathologically involved lymph nodes was performed. Mean follow-up from the time of LND was 54 months (range: 12-306 months). Lymph node basins dissected included the neck (56 patients), axilla (160 patients), and groin (122 patients). Two hundred fifty-three patients (75%) underwent therapeutic LND for clinically involved nodes, while 85 patients (25%) had elective dissections. Forty-four percent of patients received adjuvant systemic therapy. No patients received adjuvant radiotherapy to the lymph node basin. RESULTS: Overall and disease-specific survival for all patients at 10 years was 30% and 36%, respectively. Overall nodal basin recurrence was 30% at 10 years. Mean time to nodal basin recurrence was 12 months (range: 2-78 months). Site of nodal involvement was prognostic with 43%, 28%, and 23% nodal basin recurrence at 10 years with cervical, axillary, and inguinal involvement, respectively (p = 0.008). Extracapsular extension (ECE) led to a 10-year nodal basin failure rate of 63% vs. 23% without ECE (p < 0.0001). Patients undergoing a therapeutic dissection for clinically involved nodes had a 36% failure rate in the nodal basin at 10 years, compared to 16% for patients found to have involved nodes after elective dissection (p = 0.002). Lymph nodes larger than 6 cm led to a failure rate of 80% compared to 42% for nodes 3-6 cm and 24% for nodes less than 3 cm (p < 0.001). The number of lymph nodes involved also predicted for nodal basin failure with 25%, 46%, and 63% failure rates at 10 years for 1-3, 4-10, and > 10 nodes involved (p = 0.0001). There was no significant difference in nodal basin control in patients with synchronous or metachronous lymph node metastases, nor in patients receiving or not receiving adjuvant systemic therapy. Nodal basin failure was predictive of distant metastasis with 87% of patients with nodal basin recurrence developing distant disease compared to 54% of patients without nodal failure (p < 0.0001). On multivariate analysis, number of positive nodes and type of dissection (elective vs. therapeutic) were significant predictors of overall and disease-specific survival. Size of the largest lymph node was also predictive of disease-specific survival. Site of nodal involvement and ECE were significant predictors of nodal basin failure. CONCLUSIONS: Malignant melanoma patients with nodal involvement have a significant risk of nodal basin failure after LND if they have cervical involvement, ECE, >3 positive lymph nodes, clinically involved nodes, or any node larger than 3 cm. Patients with these risk factors should be considered for adjuvant radiotherapy to the lymph node basin to reduce the incidence of nodal basin recurrence. Patients with nodal basin failure are at higher risk of developing distant metastases.

Sinonasal lymphoma: a clinicopathologic analysis of 58 cases from the Massachusetts General Hospital.

Few large series compare lymphomas of the nasal cavity with those of the paranasal sinuses. We studied the cases of 58 patients, 34 males and 24 females, aged 7 to 92 years (mean, 57 years), who had lymphoma involving the nasal cavity or paranasal sinuses. Thirty-three patients had diffuse large B-cell lymphoma (DLBCL). Twenty-three were male and 10 were female, with an age range of 7 to 91 years (mean, 63 years); two were HIV-positive. Only 2 of 11 cases tested (one in an HIV-positive patient and one of lymphomatoid granulomatosis type) were Epstein-Barr virus (EBV)-positive. Thirty (91%) involved paranasal sinuses, 10 with nasal involvement, whereas three cases had nasal, but not sinus, involvement. At last follow-up, 16 (67%) were free of disease 7 to 169 months later (mean, 65 months), and 8 (33%) had died of disease 2 to 166 months later (mean, 45 months). Seventeen patients had nasal-type natural killer (NK)/T-cell lymphoma. There were 10 women and 7 men, aged 27 to 78 years (mean, 48 years). Thirteen of 14 were EBV-positive. Sixteen patients had nasal involvement, eight with sinus involvement. Eleven (73%) of 15 were alive and well 6 to 321 months later (mean, 139 months), three (20%) died of lymphoma 1, 11, and 12 months later, and one (7%) is alive with disease. There was one case each of marginal zone B-cell lymphoma, Burkitt's lymphoma, Burkitt-like lymphoma, peripheral T-cell lymphoma of unspecified type, and adult T-cell lymphoma/leukemia. In an additional three cases, the lymphomas were composed predominantly of large cells, but no immunophenotyping could be performed for subclassification. In 19 cases (17 DLBCLs, 1 Burkitt-like lymphoma, and 1 lymphoma of uncertain lineage), presenting symptoms included complaints related to the eyes. In 16 cases (13 DLBCLs, 1 Burkitt-like lymphoma, 1 nasal NK/T-cell lymphoma, and 1 lymphoma of uncertain lineage), the orbit was invaded by lymphoma. In our series, the most common lymphoma to arise in the sinonasal area is DLBCL, followed by nasal NK/T-cell lymphoma. Comparison of these two types of lymphoma showed that lymphomas involving sinuses without nasal involvement were predominantly DLBCLs (20 of 21), whereas nasal cavity lymphomas without sinus involvement were usually NK/T-cell type (8 of 11) (p = 0.000125). Compared with patients with DLBCL, patients with nasal NK/T-cell lymphoma were overall younger, with a lower male-to-female ratio. Lymphomas of B-cell lineage were more likely to be associated with symptoms related to the eyes (p < 0.0005) and to have extension to the orbit (p < 0.01) than were lymphomas of T- or NK-cell lineage. In contrast to results of Asian studies in which nasal NK/T-cell lymphoma has a very poor prognosis, our nasal NK/T-cell lymphomas had an outcome similar to that of DLBCL.

Intensive language learning and increases in rapid eye movement sleep: evidence of a performance factor.

Ten anglophone students taking a 6-week French immersion course were recorded in the sleep laboratory during 4 consecutive nights before the course, during the course and after the course. There was a positive and significant (P less than 0.05) correlation between language learning efficiency and increases in the percentage of rapid eye movement (REM) sleep from pre-course to course periods. This observation suggests that learning performance may be an important factor in the relationship between information processing and REM sleep.

Wires should not be used routinely on skin scars for mammograms after breast-conserving surgery.

The accuracy of skin wire markers on surgical incision scars during mammography to locate the primary tumor excision site was prospectively determined for 100 women. The shortest distance between the excision site and skin scar wire on either the craniocaudal or mediolateral oblique projection was 10 mm or greater in 48 per cent of patients and 20 mm or greater in 30 per cent of patients. Wire markers placed on skin incision scars during mammography after breast-conserving surgery are inadequate for the localization of the primary excision site and should not be used routinely.

Neuropsychologic deficits and clinical features of posttraumatic temporomandibular disorders.

Previous studies have shown that characteristics of posttraumatic temporomandibular disorders (pTMD) differ considerably from those of nontraumatic or idiopathic temporomandibular disorders (iTMD). Both the rate of recovery and the amount of treatment required appear to be different for both groups. In this blinded study, 14 patients with iTMD and 13 patients with pTMD were examined. Patients submitted to a variety of reaction-time tests and neuropsychologic assessments to test their ability to cope with simple and more complex tasks with and without a variety of cognitive interferences. Clinical examination was used to assess signs of TMD. Eleven of the subjects (six iTMD, five pTMD) consented to a second phase of the investigation, whereby the patients were studied with single-photon emission computerized tomography (SPECT) using 99mTc-hexamethylpropyleneamineoxime (HMPAO). For simple and complex reaction-time tests, the pTMD group was significantly slower than the iTMD group (P < .05 to P < .001). Other neuropsychologic assessment tools such as the Consonant Trigram Test and the California Verbal Learning Test indicated that pTMD patients were more affected by both proactive and retroactive interferences and were more likely to perseverate on a single thought. In clinical examination, pTMD patients demonstrated greater reaction to muscle palpation than did iTMD patients (P < .05). The SPECT results suggested that there were mild differences between the two populations, and further ther studies are required to confirm this finding. The results lend support to the concept that there are differences between pTMD and iTMD populations. It is suggested that although patients with pTMD may have some similarities to those with iTMD, the former population may benefit from being handled somewhat differently and should be assessed and treated using a more broad, multidisciplinary treatment paradigm. These results must be confirmed in studies of larger populations.

Partial lung shield for TBI.

In this study, AP/PA setup was used with a 4 MV linear accelerator. The prescribed dose is 1000 cGy, with a dose per fraction of 200 cGy. One of the simplest lung dose determinations is the nomograph relating dose correction factor and patient thickness. To save time in taking port film in every treatment, lung block is used in alternating fashion: anterior blocks are used in the second and fourth fraction and posterior block is used in the third and fifth fraction. If we set the average correction factor for the lower density lung to 1.18, the six open fields will deliver an average of 708 cGy to the lung. To limit the lung dose to 10 Gy, each blocked field should deliver 73 cGy. Measurements showed that a thickness of slightly less than 1 cm of cerrobend provides approximately 65% transmission, which approximates the desired 73% broad beam transmission. The proper transmission of the partial lung shield is verified by measurements made for the patients with diodes placed at the entrance and the exit side of the lung. While we describe a particular setup, the procedure can be modified to accommodate different dose fraction. There are many ways to deliver the TBI dose, and the method of constructing the partial lung shield described here is one of the many methods that may be used to limit the dose to the lung.

Comparison of the homogeneity of breast dose distributions with and without the medial wedge.

Radiation of the intact breast often requires medial and lateral wedges to improve dose homogeneity of its pyramidal shape and to achieve acceptable cosmesis. There is some concern that radiation scatter from the medial wedge may contribute to cancer in the uninvolved breast, yet treatment without the medial wedge is associated with inhomogeneity of magnitudes that affect cosmesis. These homogeneities are identified on treatment plans generated at the central axis (CAX). It is not known if comparing isodose curves at the central axis reflect homogeneity in superior and inferior planes. A study was undertaken to both examine inhomogeneity with and without the medial wedge, and to determine if plan selection at the CAX was representative of homogeneity above and below the CAX. Ten consecutive patients with early breast cancers had cranial, CAX, and caudal CT images of each breast compared with two wedging conditions, lateral only (LW) and medial and lateral wedged conditions (dual wedges = DW). Dosimetry was optimized at the CAX for DW and LW conditions. Dose distributions and hot spots relative to prescribed dose were compared for cranial, CAX, and caudal images. Mean chest wall separations were measured. Six of ten patients had equivalent LW and DW distributions at the levels examined. Only one of these patients had a single off-axis hot spot > 20%. Six patients had comparable LW and DW dosimetry and acceptable hot spots at the central axis, as well as chest wall separations < or = 22 cm. In conclusion, if isodose configurations are commensurate at the CAX, these patients will have homogeneity above and below the CAX. In patients with chest wall separations < or = 22 cm, treatment without the medial wedge is feasible, sparing the contralateral breast dose with little compromise to inhomogeneity in the treated breast.

Assessment of rotating-jaw traps to humanely kill raccoons (Procyon lotor).

Rotating-jaw traps (Conibear 280 and Sauvageau 2001-8, and mechanically improved models) failed to render irreversibly unconscious in < or = 3 min raccoons (Procyon lotor) immobilized with ketamine hydrochloride and struck in the head-neck region. It is unlikely that these traps, and the less powerful Conibear 220, have the potential to humanely kill raccoons.

Evaluation of the Bionic trap to quickly kill mink (Mustela vison) in simulated natural environments.

The Bionic trap, with a bait placed at the back of a 6 cm aperture plastic cone, successfully killed nine of nine wild mink (Mustela vison) in simulated natural conditions. The average times to loss of consciousness and heartbeat were estimated at less than 60 (+/- 26) sec and 340 (+/- 55) sec, respectively, after firing the trap. This study confirmed that the Bionic trap can be expected to render greater than 79% of captured mink unconscious in less than or equal to 3 min (P less than 0.05).

Evaluation of mechanically improved Conibear 220 traps to quickly kill fisher (Martes pennanti) in simulated natural environments.

Mechanically improved Conibear 220 traps failed to render irreversibly unconscious in < or = 3 min fishers single-struck in the head-neck region, or double-struck in the neck and thorax regions. Although the Conibear 220 trap is often recommended as an alternative to the steel leghold trap, it is unlikely that it has the potential to humanely kill fisher.

Evaluation of the Bionic trap to quickly kill fisher (Martes pennanti) in simulated natural environments.

The Bionic trap equipped with a 10 cm aperture bait cone and cocked to eight notches quickly killed nine of nine fishers (Martes pennanti) in simulated natural conditions. Mean (+/- SE) estimated times to loss of consciousness and heartbeat were < or = 55 sec and 305 (+/- 8) sec, respectively after firing the trap. This study confirmed that the Bionic trap can be expected to render > or = 70% of captured fishers irreversibly unconscious in < or = 3 min (P < 0.05).

Assessment of the Kania trap to humanely kill red squirrels (Tamiasciurus hudsonicus) in enclosures.

The Kania trap equipped with side wings and baited with a pine cone quickly killed nine of nine red squirrels (Tamiasciurus hudsonicus) in enclosures. Mean times to loss of consciousness and heartbeat were estimated at < or = 65 sec and < or = 91 sec, respectively, after firing the trap. Thus the Kania can be expected to render > or = 70% of captured red squirrels irreversibly unconscious in < or = 3 min (P < 0.05).

The C120 Magnum with pan trigger: a humane trap for mink (Mustela vison).

The C120 Magnum trap, equipped with a 66 x 69 mm pan trigger, which favored double strikes in the neck and thorax regions, successfully killed nine of nine wild mink (Mustela vison) in simulated natural conditions. Average times to loss of consciousness and heartbeat were estimated at less than 72 (+/- 24) sec and 158 (+/- 48) sec, respectively, after firing of the trap. This study confirmed that the C120 Magnum trap can be expected to render greater than 79% of all captured mink unconscious in less than or equal to 3 min (P less than 0.05). This is the first mink kill trap to meet the requisites of the Canadian General Standards Board regarding killing traps.

A humane killing trap for lynx (Felis lynx): the Conibear 330 with clamping bars.

The Conibear 330 failed to render irreversibly unconscious in < or = 3 min one lynx (Felis lynx) struck in the shoulders and two of eight lynx struck in the neck region, in simulated natural environments. A Conibear 330 with two clamping bars rendered unconscious in < or = 3 min eight lynx struck in the neck and one struck in the shoulders. The mean (+/- SE) times to loss of consciousness and heartbeat were 67.2 (+/- 4.0) sec and 196.0 (+/- 10.4) sec, respectively. This modified Conibear 330 can be expected to render > or = 70% of captured lynx irreversibly unconscious in < or = 3 min (P < 0.05).

Injuries and behavior of raccoons (Procyon lotor) captured in the Soft Catch and the EGG traps in simulated natural environments.

The behavior and injuries of raccoons held for 12 and 24 hr in the Soft Catch and the EGG traps were studied in simulated natural environments. Nine raccoons held for 12 hr in the Soft Catch received minor injuries. However, one of nine raccoons held for 24 hr in this trap mutilated itself. The EGG trap caused only minor injuries to nine raccoons held for 12 hr, and nine others held for 24 hr. Thus the EGG trap can be expected, at a 95% level of confidence, to hold > or = 70% of the raccoons on traplines for 24 hr without serious injury. Raccoons captured in the Soft Catch fought their surroundings more than the trap. Those captured in the EGG trap fought the trap more than their surroundings. During the 24-hr capture study, escape behavior was more intense during the first 12 hr of capture, during both day and night.