Soil water storage in an upland forest after selective logging in Central Amazonia

Soil water storage of Central Amazonian soil profiles in upland forest plots subjected to selective logging (in average, 8 trees or 34, 3 m³ of timber per hectare were removed) was measured in four layers, down to a depth of 70 cm. The study lasted 27-months and was divided in two phases: measurements were carried out nearly every week during the first 15 months; in the following year, five intensive periods of measurements were performed. Five damage levels were compared: (a) control (undisturbed forest plot); (b) centre of the clearing/gap; (c) edge of the gap; (d) edge of the remaining forest; and (e) remaining forest. The lowest values for water storage were found in the control (296 ± 19.1 mm), while the highest were observed (333 ± 25.8 mm) in the centre of the gap, during the dry period. In the older gaps (7.5-8.5 year old), soil water storage was similar to the remaining and the control forest, indicating a recovery of hydric soil properties to nearly the levels prior to selective logging.

Improved IL-2 immunotherapy by selective stimulation of IL-2 receptors on lymphocytes and endothelial cells.

IL-2 immunotherapy is an attractive treatment option for certain metastatic cancers. However, administration of IL-2 to patients can lead, by ill-defined mechanisms, to toxic adverse effects including severe pulmonary edema. Here, we show that IL-2-induced pulmonary edema is caused by direct interaction of IL-2 with functional IL-2 receptors (IL-2R) on lung endothelial cells in vivo. Treatment of mice with high-dose IL-2 led to efficient expansion of effector immune cells expressing high levels of IL-2Rbetagamma, including CD8(+) T cells and natural killer cells, which resulted in a considerable antitumor response against s.c. and pulmonary B16 melanoma nodules. However, high-dose IL-2 treatment also affected immune cell lineage marker-negative CD31(+) pulmonary endothelial cells via binding to functional alphabetagamma IL-2Rs, expressed at low to intermediate levels on these cells, thus causing pulmonary edema. Notably, IL-2-mediated pulmonary edema was abrogated by a blocking antibody to IL-2Ralpha (CD25), genetic disruption of CD25, or the use of IL-2Rbetagamma-directed IL-2/anti-IL-2 antibody complexes, thereby interfering with IL-2 binding to IL-2Ralphabetagamma(+) pulmonary endothelial cells. Moreover, IL-2/anti-IL-2 antibody complexes led to vigorous activation of IL-2Rbetagamma(+) effector immune cells, which generated a dramatic antitumor response. Thus, IL-2/anti-IL-2 antibody complexes might improve current strategies of IL-2-based tumor immunotherapy.

La substitution hormonale et ses dérivés dans la prévention et le traitement de l'ostéoporose [Hormone replacement therapy and its derivatives in the prevention and treatment of osteoporosis]

Hormone replacement therapy (HRT) is an established approach for the treatment and the prevention of osteoporosis. Many studies with bone mineral density as primary outcome have shown significant efficacy. Observational studies have indicated a significant reduction of hip fracture risk in cohorts of women who maintained HRT therapy. The Women's Health Initiative is the first prospective randomised controlled study which showed a positive effect of HRT in terms of reduction of vertebral and hip fractures risk. Unfortunately, this study has been interrupted after 5.2 years because of the unsupportable increase of risk of cardiovascular disease and breast cancer. Compliance with HRT, however, is typically poor because of the potential side effects and possible increased risk of breast or endometrial cancer. Nevertheless, there is now evidence that lower doses of estrogens in elderly women may prevent bone loss while minimizing the side effects seen with higher doses. Combination therapies using low doses estrogen should probably be reserved for patients who continue to fracture on single therapy. Selective estrogen receptor modulators (SERMs) are very interesting drugs. The goal of these agents is to maximize the beneficial effect of estrogen on bone and to minimize or antagonize the deleterious effects on the breast and endometrium. Raloxifene, approved for the prevention and the treatment of osteoporosis, has been shown to reduce the risks of vertebral fracture in large clinical trials. However, they don't reduce non vertebral fractures. Tibolone is a synthetic steroid that increased bone mineral density at lumbar spine and femoral neck. But no trial has been performed with fractures as end point.

Adenosquamous carcinoma of the head and neck: report of 20 cases and review of the literature.

PURPOSE: To assess the clinical profile and prognostic factors in patients with adenosquamous carcinoma (ASC) of the head and neck treated by surgery and/or radiation therapy with or without chemotherapy. METHODS: Data from 20 patients with stage I-II (n = 4), III (n = 5), or IVA (n = 11) head and neck ASC, treated between 1989 and 2010 were collected in a retrospective multicenter Rare Cancer Network study. Surgery was performed in 16 patients. Seventeen patients received combined modality treatment. RESULTS: After a median follow-up of 15.5 months, 12 patients recurred. The 3-year and median overall survival, disease-free survival (DFS), and loco-regional control were 52% and 39 months, 32% and 12 months, and 47% and 33 months respectively. In multivariate analysis, DFS was negatively influenced by the presence of extracapsular extension and advanced stage. CONCLUSION: Overall prognosis of locoregionally advanced ASC remains poor. However, early stage ASC patients managed with combined modality treatment may have prolonged DFS.

RF pulse concatenation for spatially selective inversion

It is shown that spatially selective inversion and saturation can be achieved by concatenation of RF pulses with lower flip angles. A concatenation rule which enables global doubling of the flip angle of any given excitation pulse applied to initial z magnetization is proposed. In this fashion, the selectivity of the single pulse is preserved, making the high selectivity achievable in the low flip-angle regime available for inversion and large flip-angle saturation purposes. The profile quality achievable with exemplary concatenated pulses is investigated in comparison with adiabatic inversion. It is verified that by using concatenated inversion in the transfer insensitive labeling technique (TILT), the MT artifact is suppressed. Copyright 2000 Academic Press.

A selective nociceptive block is not sufficient to prevent central changes after peripheral nerve injury

Background: Providing analgesia without suppressing motor or sensory function is a challenge for regional anesthesia and postoperative pain management. Resiniferatoxin (RTX), an ultrapotent agonist for transient receptor potential subtype-1 (TRPV1) can produce this selective blockade, as TRPV1 is selectively expressed on nociceptors. Futhermore, after peripheral nerve injury, spontaneous ectopic activity arises from all types of nerve fibers that can affect spinal neurons and glial cells. The goal of the present experiment is to determine whether spontaneous activity generated in C-fibers or in both A&C-fibers is required for microglia activation. Method: We applied RTX (0.01%) or bupivacaine microspheres to the sciatic nerve of rats to block the conduction of C-fibers or A&C-fibers, respectively, before spared nerve injury (SNI). Behavior was tested and all the rats were sacrificed 2 days later; immunohistochemistry was performed on their spinal cord for mitogen-activated protein kinase (MAPK) p38, bromodeoxyuridine (BrdU, marker of proliferation) and Iba1 (microglial marker). Result: At day 2 after SNI robust mechanical allodynia and p38 activation in spinal microglia were documented. There was also a substantial cell proliferation in the spinal cord, all proliferating cells (BrdU+) being microglia (Iba1+). RTX blocked heat sensitivity and produced heat hypoalgesia without affecting mechanical allodynia and motor function. Microglial proliferation and p38 activation in the spinal cord were not affected by RTX (p >0.05). In contrast, a complete sensory and motor blockade was seen with bupivacaine which also significantly inhibited p38 activation and microglial proliferation in the spinal cord (p <0.05). Conclusion: We conclude that (1) RTX can provide a selective nociceptive blockade but that (2) blocking only nociceptive fibers does not impair the development of mechanical allodynia and microglia activation. Therefore (3) if microglia activation is important for chronic pain development then specific nociceptive blockade won't be sufficient to prevent it.

Selective expression of a dominant-negative form of peroxisome proliferator-activated receptor in keratinocytes leads to impaired epidermal healing.

Many nuclear hormone receptors are involved in the regulation of skin homeostasis. However, their role in the epithelial compartment of the skin in stress situations, such as skin healing, has not been addressed yet. The healing of a skin wound after an injury involves three major cell types: immune cells, which are recruited to the wound bed; dermal fibroblasts; and epidermal and hair follicle keratinocytes. Our previous studies have revealed important but nonredundant roles of PPARalpha and beta/delta in the reparation of the skin after a mechanical injury in the adult mouse. However, the mesenchymal or epithelial cellular compartment in which PPARalpha and beta/delta play a role could not be determined in the null mice used, which have a germ line PPAR gene invalidation. In the present work, the role of PPARalpha was studied in keratinocytes, using transgenic mice that express a PPARalpha mutant with dominant-negative (dn) activity specifically in keratinocytes. This dn PPARalpha lacks the last 13 C terminus amino acids, binds to a PPARalpha agonist, but is unable to release the nuclear receptor corepressor and to recruit the coactivator p300. When selectively expressed in keratinocytes of transgenic mice, dn PPARalphaDelta13 causes a delay in the healing of skin wounds, accompanied by an exacerbated inflammation. This phenotype, which is similar to that observed in PPARalpha null mice, strongly suggests that during skin healing, PPARalpha is required in keratinocytes rather than in other cell types.

FLIP prevents apoptosis induced by death receptors but not by perforin/granzyme B, chemotherapeutic drugs, and gamma irradiation.

FLICE-inhibitory protein, FLIP (Casper/I-FLICE/FLAME-1/CASH/CLARP/MRIT), which contains two death effector domains and an inactive caspase domain, binds to FADD and caspase-8, and thereby inhibits death receptor-mediated apoptosis. Here, we characterize the inhibitory effect of FLIP on a variety of apoptotic pathways. Human Jurkat T cells undergoing Fas ligand-mediated apoptosis in response to CD3 activation were completely resistant when transfected with FLIP. In contrast, the presence of FLIP did not affect apoptosis induced by granzyme B in combination with adenovirus or perforin. Moreover, the Fas ligand, but not the perforin/granzyme B-dependent lytic pathway of CTL, was inhibited by FLIP. Apoptosis mediated by chemotherapeutic drugs (i.e., doxorubicin, etoposide, and vincristine) and gamma irradiation was not affected by FLIP or the absence of Fas, indicating that these treatments can induce cell death in a Fas-independent and FLIP-insensitive manner.

Cataractogenesis after total body irradiation.

PURPOSE: To evaluate the prognostic factors and the ophthalmologic follow-up on cataract formation following total body irradiation (TBI) prior to bone marrow transplantation (BMT). METHODS AND MATERIALS: Between 1980 and 1992, 494 patients were referred to our department for TBI prior to BMT. The mean age was 32 +/- 11 (median: 32, range: 2-63) years and the male to female ratio was 1.6 (304:190). The majority of patients were treated for acute leukemia (lymphoblastic, n = 177, 36%; or nonlymphoblastic , n = 139, 28%); 80 (16%) for chronic myeloid leukemia, 60 (12%) for non-Hodgkin's lymphoma, 23 (5%) for multiple myeloma, and 15 (3%) for other malignancies. Two hundred and fifty-four (51%) patients were grafted in the first complete remission (CR), 118 (24%) in second CR. Allogenic BMT was performed in 210 (43%) patients, and autologous BMT in 284 (57%). Methotrexate combined to steroids (n = 47, 22%) or to cyclosporine (n = 163, 78%) was administered for graft-versus-host disease (GvHD) prophylaxis. In 188 patients (38%), heparin was used in the prevention of veno-occlusive disease (VOD) of the liver. Furthermore, steroid administration was registered in 223 (45%). The conditioning chemotherapy consisted of cyclophosphamide (Cy) alone in 332 (67%) patients. Total-body irradiation was administered either in single dose (STBI; 10 Gy in 1 day, n = 291) or in six fractions (FTBI; 12 Gy over 3 consecutive days, n = 203) before BMT. The mean instantaneous dose rate was 0.0574 +/- 0.0289 Gy/min (0.024-0.1783). It was < 0.048 Gy/min in 157 patients (LOW group), > or = 0.048 Gy/min and <0.09 Gy/min in 301 patients (MEDIUM group), and > or = 0.09 Gy/min in 36 patients (HIGH group). RESULTS: When considering all patients, 42 (8.5%) patients developed cataracts after 13 to 72 months (median: 42 months) with a 5-year estimated cataract incidence (ECI) of 23%. Thirty-three (11.3%) out of 291 patients in the STBI group, and 9 (4.4%) out of 203 patients in the FTBI group developed cataracts with 5-year estimated incidences of 34 and 11%, respectively (p = 0.0004). Seven (19.4%) out of 36 patients in the HIGH group, 33 (10.9%) out of 301 in the MEDIUM group, and 2 (1.2%) out of 157 in the LOW group developed cataracts with respective 5-year cataract incidences of 54%, 30%, and 3.5% (HIGH vs. MEDIUM, p = 0.07; MEDIUM vs. LOW, p = 0.0001; HIGH vs. LOW, p < 0.0001). On the other hand, patients who received heparin as prophylactic treatment against VOD of the liver had less cataracts than those who did not receive (5-year ECI of 16% vs. 28%, respectively; p = 0.01). There was no statistically significant difference in terms of 5-year ECI according to age, sex, administration of steroids, GvHD prophylaxis, type of BMT, or previous cranial radiotherapy in children. Multivariate analysis revealed that the instantaneous dose rate (p = 0.001), and the administration of heparin against VOD (p = 0.05) were the two independent factors influencing the cataract incidence, while age, fractionation, and use of steroids were not. Among the 42 patients who developed cataracts, 38 had bilateral extracapsular cataract extraction and intraocular lens implantation, and only 4 (10%) developed secondary cataracts in a median follow-up period of 39 months. CONCLUSION: Among the abovementioned TBI parameters, high instantaneous dose rate seems to be the main risk factor of cataract formation, and the administration of heparin appears to have a protective role in cataractogenesis. On the other hand, ionizing radiation seems to have a protective effect on posterior capsule opacification following extracapsular cataract extraction and intraocular lens implantation.

Outcome and Prognostic Factors in Adenosquamous Carcinoma of the Head and Neck: A Multicenter Rare Cancer Network Study

Purpose/Objective(s): Adenosquamous carcinoma (AC) of the head and neck is a distinct entity first described in 1968. Its natural history is more aggressive than squamous cell carcinoma but this is based on very small series reported in the literature. The goal of this study was to assess the clinical profile, outcome, patterns of failure and prognostic factors in patients with AC of the head and neck treated by radiation therapy (RT) with or without chemotherapy (CT).Materials/Methods: Data from 18 patients with Stage I (n = 3), II (n = 1), III (n = 4), or IVa (n = 10) AC, treated between 1989 and 2009, were collected in a retrospective multicenter Rare Cancer Network study. Median age was 60 years (range, 48 - 73 years). Fourteen patients were male and 4 female. Risk factors, including perineural invasion, lymphangitis, vascular invasion, positive margins, were present in 83% of the patients. Tumor sites included oral cavity in 4, oropharynx in 4, hypopharynx in2, larynx in 2, salivary glands in 2, nasal vestibule in 2, nasopharynx in 1, and maxillary sinus in 1 patient. Surgery (S) was performed in all but 5 patients. S alone was performed in only 1 patient, and definitive RT alone in 3 patients. Fourteen patients received combined modality treatment (S+RT in 10, RT+CT in 2, and all of the three modalities in 2 patients). Median RT dose to the primary and to the nodes was 66 Gy (range, 50 - 72 Gy) and 53 Gy (range, 44 - 66 Gy), respectively (1.8 - 2.0 Gy/fr., 5 fr./ week). In 4 patients, the planning treatment volume included the primary tumor site only. Seven patients were treated with 2D RT, 7 with 3D conformal RT, and 2 with intensity-modulated RT.Results: After a median follow-up period of 38 months (range, 9 - 62 months), 8 patients developed distant metastases (lung, bone, mediastinum, and liver), 6 presented nodal recurrences, and only 4 had a local relapse at the primary site (all in-field recurrences). At last follow-up, 6 patients were alive without disease, 1 alive with disease, 9 died from progressive disease, and 2 died from intercurrent disease. The 3-year and median overall survival, disease-free survival (DFS) and locoregional control rates were 52% (95% confidence interval [CI]: 28 - 76%) and 39 months, 36% (95% CI: 13 - 49%) and 12 months, and 54% (95% CI: 26 - 82%) and 40 months, respectively. In multivariate analysis (Cox model), DFS was negatively influenced by the presence of extracapsular extension (p = 0.02) and advanced stage (IV versus I-III, p = 0.003).Conclusions: Overall prognosis of locoregionally advanced AC remains poor, and distant metastases and nodal relapse occur in almost half of the cases. However, local control is relatively good, and early stage AC patients had prolonged DFS when treated with combined modality treatment.

Psychometric characteristics of the Spanish version of instruments to measure neck pain disability

Background: The NDI, COM and NPQ are evaluation instruments for disability due to NP. There was no Spanish version of NDI or COM for which psychometric characteristics were known. The objectives of this study were to translate and culturally adapt the Spanish version of the Neck Disability Index Questionnaire (NDI), and the Core Outcome Measure (COM), to validate its use in Spanish speaking patients with non-specific neck pain (NP), and to compare their psychometric characteristics with those of the Spanish version of the Northwick Pain Questionnaire (NPQ).Methods: Translation/re-translation of the English versions of the NDI and the COM was done blindly and independently by a multidisciplinary team. The study was done in 9 primary care Centers and 12 specialty services from 9 regions in Spain, with 221 acute, subacute and chronic patients who visited their physician for NP: 54 in the pilot phase and 167 in the validation phase. Neck pain (VAS), referred pain (VAS), disability (NDI, COM and NPQ), catastrophizing (CSQ) and quality of life (SF-12) were measured on their first visit and 14 days later. Patients' self-assessment was used as the external criterion for pain and disability. In the pilot phase, patients' understanding of each item in the NDI and COM was assessed, and on day 1 test-retest reliability was estimated by giving a second NDI and COM in which the name of the questionnaires and the order of the items had been changed.Results: Comprehensibility of NDI and COM were good. Minutes needed to fill out the questionnaires [median, (P25, P75)]: NDI. 4 (2.2, 10.0), COM: 2.1 (1.0, 4.9). Reliability: [ICC, (95%CI)]: NDI: 0.88 (0.80, 0.93). COM: 0.85 (0.75,0.91). Sensitivity to change: Effect size for patients having worsened, not changed and improved between days 1 and 15, according to the external criterion for disability: NDI: -0.24, 0.15, 0.66; NPQ: -0.14, 0.06, 0.67; COM: 0.05, 0.19, 0.92. Validity: Results of NDI, NPQ and COM were consistent with the external criterion for disability, whereas only those from NDI were consistent with the one for pain. Correlations with VAS, CSQ and SF-12 were similar for NDI and NPQ (absolute values between 0.36 and 0.50 on day 1, between 0.38 and 0.70 on day 15), and slightly lower for COM (between 0.36 and 0.48 on day 1, and between 0.33 and 0.61 on day 15). Correlation between NDI and NPQ: r = 0.84 on day 1, r = 0.91 on day 15. Correlation between COM and NPQ: r = 0.63 on day 1, r = 0.71 on day 15.Conclusion: Although most psychometric characteristics of NDI, NPQ and COM are similar, those from the latter one are worse and its use may lead to patients' evolution seeming more positive than it actually is. NDI seems to be the best instrument for measuring NP-related disability, since its results are the most consistent with patient's assessment of their own clinical status and evolution. It takes two more minutes to answer the NDI than to answer the COM, but it can be reliably filled out by the patient without assistance.