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.

Immunodomination results from functional differences between competing CTL.

The presence of dominant epitopes suppresses generation of CTL activity toward other non-dominant epitopes found on the same antigen-presenting cell (APC). This phenomenon, termed immunodomination, drastically restricts the diversity of the repertoire of CTL responses. Under various experimental conditions we assessed the in vivo expansion by tetramer staining and function by expression of O-glycans and intracellular perforin of CTL specific for a dominant (B6(dom1)) and a non-dominant (HY) H2D(b)-restricted epitope. Immunodomination abrogated expansion rather than differentiation of HY-specific CTL. When immunodomination was precluded because HY was presented alone or because high numbers of antigen-bearing APC were present, the numbers of HY-specific T cells detected after antigen priming were similar to those of B6(dom1)-specific T cells. The main difference between T cells that recognized B6(dom1) versus HY was functional rather than quantitative. The key feature of T cells specific for B6(dom1) is that they show striking up-regulation of molecules involved in CTL effector activity rather than accumulating to particularly high levels, as assessed by tetramer staining. These results support the emerging concept that following antigen priming, CTL populations of similar size can display important differences in effector function, and suggest that these functional differences are instrumental in shaping the repertoire of CTL responses.

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.

Internal mammary lymph node inclusion in standard tangent breast fields: effects of body habitus.

The purpose of this study was to determine the variability of internal mammary node (IMN) coverage with standard breast tangent fields using surface anatomy as determined by computed tomography (CT) planning for patients treated with either breast-conserving treatment or postmastectomy, and to evaluate the influence of body habitus and shape on IMN coverage with standard tangent fields. This prospective study included consecutive women with breast cancer who underwent either local excision or mastectomy and had standard tangent fields intended to cover the breast plus a margin simulated using surface anatomy. CT planning determined the location of the IMN with respect to the tangent fields designed from surface anatomy. The internal mammary vessels were used as surrogates for the IMNs. CT measurements of the presternal fat thickness and anteroposterior (AP) and transverse skeletal diameters were made to determine their relationship to the inclusion of IMNs within the tangent fields. Only seven patients (14%) had their IMNs completely within the tangent fields. Twenty patients (40%) had partial coverage of their IMNs, and 23 (46%) had their IMNs completely outside the fields. IMN inclusion was inversely correlated with presternal fat thickness. Thoracic skeletal shape was not associated with IMN inclusion. Standard tangent fields generally do not cover the IMNs completely but may cover them at least partially in a majority of patients. The presternal fat thickness is inversely correlated with IMN inclusion in the tangent fields.

Risk factors for nodal recurrence after lymphadenectomy for melanoma.

BACKGROUND: The risk and outcome of regional failure after elective and therapeutic lymph node dissection (ELND/TLND) for microscopically and macroscopically involved lymph nodes without adjuvant radiotherapy were evaluated. METHODS: Retrospective melanoma database review of 338 patients (ELND 85, TLND 253) from 1970 to 1996 with pathologically involved lymph nodes. RESULTS: Regional recurrence occurred in 14% of patients treated with ELND (n = 12) and 28% of patients treated with TLND (n = 72; P = .009). Risk factors associated with nodal recurrence were advanced age, primary lesion in the head and neck region, depth of the primary lesion, number of involved lymph nodes, and extracapsular extension (ECE). For each nodal basin, the ELND group had a lower incidence of recurrence than the TLND group. The TLND group had larger lymph nodes, greater number of involved lymph nodes, and a higher incidence of ECE. The 10-year disease-specific survival was 51% vs. 30% for ELND and TLND, respectively (P = .0005). Nodal basin failure was predictive of distant metastasis, with 87% developing distant disease compared with 54% of patients without nodal recurrence (P < .0001). Of six patients who underwent a second dissection after isolated nodal recurrence, five patients have had a median disease-free interval of 79 months. CONCLUSIONS: After ELND or TLND, patients who have a large tumor burden (thick primary melanoma, multiply involved lymph nodes, ECE), advanced age, and a primary lesion located in the head and neck have a significantly increased likelihood of relapse and a decreased survival. Few patients present with an isolated nodal recurrence, but the majority can be salvaged by a second dissection.

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.

Comparison of vasopeptidase inhibitor, omapatrilat, and lisinopril on exercise tolerance and morbidity in patients with heart failure: IMPRESS randomised trial.

BACKGROUND: We aimed to assess in patients with congestive heart failure whether dual inhibition of neutral endopeptidase and angiotensin-converting enzyme (ACE) with the vasopeptidase inhibitor omapatrilat is better than ACE inhibition alone with lisinopril on functional capacity and clinical outcome. METHODS: We did a prospective, randomised, double-blind, parallel trial of 573 patients with New York Heart Association (NYHA) class II-IV congestive heart failure, left-ventricular ejection fraction of 40% or less, and receiving an ACE inhibitor. Patients were randomly assigned omapatrilat at a daily target dose of 40 mg (n=289) or lisinopril at a daily target dose of 20 mg (n=284) for 24 weeks. The primary endpoint was improvement in maximum exercise treadmill test (ETT) at week 12. Secondary endpoints included death and comorbid events indicative of worsening heart failure. FINDINGS: Week 12 ETT increased similarly in the omapatrilat and lisinopril groups (24 vs 31 s, p=0.45). The two drugs were fairly well tolerated, but there were fewer cardiovascular-system serious adverse events in the omapatrilat group than in the lisinopril group (20 [7%] vs 34 [12%], p=0.04). There was a suggestive trend in favour of omapatrilat on the combined endpoint of death or admission for worsening heart failure (p=0.052; hazard ratio 0.53 [95% CI 0.27-1.02]) and a significant benefit of omapatrilat in the composite of death, admission, or discontinuation of study treatment for worsening heart failure (p=0.035; 0.52 [0.28-0.96]). Omapatrilat improved NYHA class more than lisinopril in patients who had NYHA class III and IV (p=0.035), but not if patients with NYHA class II were included. INTERPRETATION: Our findings suggest that omapatrilat could have some advantages over lisinopril in the treatment of patients with congestive heart failure. Thus use of vasopeptidase inhibitors could constitute a potentially important treatment for further improving the prognosis and well being of patients with this disorder.

Neurohormonal activation in severe heart failure: relations to patient death and the effect of treatment with flosequinan.

BACKGROUND: Flosequinan is a direct-acting vasodilator that exerts beneficial hemodynamic effects and improves the exercise tolerance of patients with heart failure. However, a multicenter trial has demonstrated that long-term administration of flosequinan is associated with increased mortality rate. To explore a possible role of neurohormonal activation on this adverse outcome, we conducted a substudy to examine the plasma levels of 3 neurohormonal systems known to have prognostic implications in heart failure. METHODS: At 20 participating Canadian centers, paired plasma samples at baseline and 1 month after randomization for the measurement of N-terminal atrial natriuretic peptide (N-ANP), angiotensin II, and norepinephrine were obtained in 234 patients (114 receiving flosequinan and 120 receiving placebo). RESULTS: Treatment with flosequinan was associated with a decline in median plasma N-ANP levels (2139 pmol/L at baseline to 1625 pmol/L at 1 month [P =. 0001]), unchanged plasma angiotensin II levels (40 to 50 pmol/L [P =. 2700]), and a modest increase in plasma norepinephrine levels (391 to 439 pg/mL [P =.002]). These changes were not observed in the placebo group. Multivariate analysis of baseline variables revealed that plasma norepinephrine level predicted patients' death whereas analysis incorporating both baseline and 1-month variables indicated that plasma N-ANP level predicted patients' death. Furthermore, in the flosequinan group, a significant decline in plasma N-ANP level was observed in the survivors only. On multivariate analysis of baseline and 1-month data, the increase in plasma norepinephrine level did not predict the increase in heart rate associated with the use of flosequinan, suggesting that the 2 effects might be mediated by separate mechanisms. CONCLUSIONS: Results of our study demonstrate that in patients with severe heart failure, baseline norepinephrine level predicts death. Flosequinan increases plasma norepinephrine level and heart rate in these patients through mechanisms that override its beneficial hemodynamic effects. Our study reinforces the concept that the direct actions of a pharmacologic agent may have a more profound impact on the prognosis of these patients than the hemodynamic effects.

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.

Thiotepa-associated cardiomyopathy during blood or marrow transplantation: association with the female sex and cardiac risk factors.

Thiotepa (TT) has not been reported to cause cardiomyopathy, whereas cyclophosphamide (Cy)-related cardiomyopathy is well characterized. To search for cases of acute onset cardiomyopathy associated with TT, we retrospectively reviewed 171 patients who received TT-containing conditioning regimens for blood or marrow transplantation (BMT). Nine of 171 patients (5.3%) developed clinical congestive heart failure in the post-BMT period. The median time to onset of heart failure was 15 days after BMT (range 5-30). The median pre-BMT left ventricular ejection fraction (LVEF) was 50% (range 42-65%) as determined by two-dimensional echocardiogram, or gated blood pool scan. At the time of cardiomyopathy onset, LVEF was 30%. Six patients died of causes unrelated to heart failure. All affected patients who developed congestive heart failure following administration of TT had some evidence of cardiac dysfunction prior to transplantation. Significant risk factors for the development of cardiomyopathy included low pre-BMT-LVEF and female sex--particularly in females receiving allogeneic transplantation. The incidence of congestive heart failure with TT-containing regimens was similar to the incidence using other regimens with and without Cy. The mean time to clinical evidence of TT-associated cardiomyopathy was longer than the mean time reported with Cy. We recommend caution in using high-dose TT-containing regimens for patients with histories of cardiac dysfunction.

Does postoperative irradiation play a role in the adjuvant therapy of stage T4 colon cancer?

PURPOSE: This study analyzes the long-term outcome of patients with stage T4 colon cancer who receive postoperative irradiation. The purpose of the study is to define the potential role of this modality with current systemic therapies. PATIENTS AND METHODS: A retrospective analysis was performed of 152 patients undergoing resection of T4 colon cancer followed by moderate- to high-dose postoperative tumor bed irradiation with and without 5-fluorouracil-based chemotherapy. Of the 152 patients, 110 patients (T4N0 or T4N+) were treated adjuvantly, whereas 42 patients received irradiation for the control of gross or microscopic residual local tumor. RESULTS: For 79 adjuvantly treated patients with stage T4N0 or T4N+ cancer with one lymph node metastasis, the 10-year actuarial rates of local control and recurrence-free survival were 88% and 58%, respectively. Results were less satisfactory for patients with more extensive nodal involvement. The 10-year actuarial rates of local control and recurrence-free survival of 39 patients with T4 tumors complicated by perforation or fistulas were 81% and 53%, respectively. For 42 patients with incompletely resected tumors, the 10-year actuarial recurrence-free survival was 19%. CONCLUSIONS: In comparison with historical controls, postoperative tumor bed irradiation improves local control for some subsets of patients. In addition to standard 5-fluorouracil-based chemotherapy, adjuvant tumor bed irradiation should be considered when colon cancers invade adjoining structures, when they are complicated by perforation or fistulas, or when they are incompletely excised at the primary site.

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.

Appendiceal carcinoma: patterns of failure following surgery and implications for adjuvant therapy.

BACKGROUND AND OBJECTIVES: Primary adenocarcinoma of the appendix is rare, which makes an understanding of its natural history difficult. To date, it is treated predominantly with surgery alone. This review aims to elucidate the patterns of failure and treatment outcomes when adjuvant treatment is given after primary surgical resection. METHODS: Twenty-three patients were treated with either surgery alone, or with surgery and adjuvant radiation +/- chemotherapy. A review of the clinical course of these patients was undertaken with an analysis of the local control, distant failure, disease-free survival, and overall survival. RESULTS: Most patients presented with local invasion or metastatic disease often involving the peritoneum. Overall survival was 32%, similar to the results of other studies. Analysis of patients with locally advanced disease showed improvement in overall survival and local control with postoperative radiation therapy compared to surgery alone. CONCLUSIONS: Adenocarcinoma of the appendix is a rare disease that presents most often in an advanced stage. It has been shown by others that a right hemicolectomy provides the best outcome with respect to surgical procedure. Postoperative irradiation appears to provide a benefit for both local control and overall survival.

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.

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).