Transmural care. A new approach in the care for terminal cancer patients: its effects on re-hospitalization and quality of life

The pharmacological properties of non-adrenergic non-cholinergic (NANC) inhibitory neurotransmission were investigated in the rabbit choledocho-duodenal junction (CDJ), using the microelectrode and tension recording methods. L-NAME (10(-4) M) and apamin (5 X 10 (-6) M) suppressed NANC relaxation evoked by electrical field stimulation (EFS) in the presence of atropine and guanethidine (each 10(-6) M) to a similar extent (to about 40% of the initial control). However, combined application of L-NAME (10(-4) M) and apamin (5 X 10(-6) M) did not abolish it. EFS also evoked biphasic inhibitory junction potentials (IJPs) consisting of initial fast and slow sustained components in the presence of atropine and guanethidine (each 10(-6) M). Apamin (5 X 10(-8)-5 X 10(-6) M) dose-dependently suppressed the initial fast component by about 70%. In contrast, L-NAME (10(-4) M) did not affect either the amplitude of IJP or the resting membrane potential. PACAP-38 (> 10(-8) M) dose-dependently hyperpolarized the smooth muscle membrane of rabbit CDJ followed by a slow repolarization to the original level. After pretreatment with apamin (5 X 10(-7) M), PACAP-38 (10(-6) M) failed to evoke membrane hyperpolarization. During repolarization in the continued presence of PACAP-38, the amplitude of initial fast component of IJP was reduced to about 40-60% of control value, while that of the slow one was unaffected. A similar suppression of initial fast component of IJP (about 40% of the control value) also occurred after application of PACAP (6-38), a PACAP antagonist, or prolonged treatment with monoclonal antibodies to PACAP-27 or PACAP-38. Furthermore, the substantial part of residual fast IJP in the presence of PACAP (6-38) was suppressed by desensitization to alpha,beta-methylene ATP (10(-3) M). These results indicate that in rabbit CDJ NANC relaxation consists mainly of apamin- and L-NAME-sensitive components, which occur in a membrane potential dependent (through membrane hyperpolarization) and independent fashion, respectively. It has further been suggested that PACAP, together with a smaller contribution of ATP, may be involved as the principal apamin-sensitive transmitter in NANC relaxation of this muscle.     

Minimal residual disease status before allogeneic bone marrow transplantation is an important determinant of successful outcome for children and adolescents with acute lymphoblastic leukemia

The efficacy of allografting in acute lymphoblastic leukemia (ALL) is heavily influenced by remission status at the time of transplant. Using polymerase chain reaction (PCR)-based minimal residual disease (MRD) analysis, we have investigated retrospectively the impact of submicroscopic leukemia on outcome in 64 patients receiving allogeneic bone marrow transplantation (BMT) for childhood ALL. Remission BM specimens were taken 6 to 81 days (median, 23) before transplant. All patients received similar conditioning therapy; 50 received grafts from unrelated donors and 14 from related donors. Nineteen patients were transplanted in first complete remission (CR1) and 45 in second or subsequent CR. MRD was analyzed by PCR of Ig or T-cell receptor delta or gamma rearrangements, electrophoresis, and allele-specific oligoprobing. Samples were rated high-level positive (clonal band evident after electrophoresis; sensitivity 10(-2) to 10(-3)), low-level positive (MRD detected only after oligoprobing; sensitivity 10(-3) to 10(-5)), or negative. Excluding 8 patients transplanted in CR2 for isolated extramedullary relapse (all MRD-), MRD was detected at high level in 12 patients, low level in 11, and was undetectable in 33. Two-year event-free survival for these groups was 0%, 36%, and 73%, respectively (P <.001). Follow-up in patients remaining in continuing remission is 20 to 96 months (median, 35). These results suggest that MRD analysis could be used routinely in this setting. This would allow identification of patients with resistant leukemia (who may benefit from innovative BMT protocols) and of those with more responsive disease (who may be candidates for randomized trials of BMT versus modern intensive relapse chemotherapy).     

Potent quinoxaline-spaced phosphono alpha-amino acids of the AP-6 type as competitive NMDA antagonists: synthesis and biological evaluation

A series of alpha-amino-3-(phosphonoalkyl)-2-quinoxalinepropanoic acids was synthesized and evaluated for NMDA receptor affinity using a [3H] CPP binding assay. Functional antagonism of the NMDA receptor complex was evaluated in vitro using a stimulated [3H]TCP binding assay and in vivo by employing an NMDA-induced seizure model. Some analogues also were evaluated in the [3H]-glycine binding assay. Several compounds of the AP-6 type show potent and selective NMDA antagonistic activity both in vitro and in vivo. In particular alpha-amino-7-chloro-3-(phosphonomethyl)-2-quinoxalinepropanoic acid (1) displayed an ED50 of 1.1 mg/kg ip in the NMDA lethality model. Noteworthy is alpha-amino-6,7-dichloro-3-(phosphonomethyl)-2-quinoxalinepropanoic++ + acid (3) with a unique dual activity, displaying in the NMDA receptor binding assay an IC50 of 3.4 nM and in the glycine binding assay an IC50 of 0.61 microM.     

Structure of the NMDA receptor channel M2 segment inferred from the accessibility of substituted cysteines

The structure of the NMDA receptor channel M2 segment was investigated by probing the extracellular and cytoplasmic faces of cysteine-substituted NR1-NR2C channels with charged sulfhydryl-specific reagents. The pattern of accessible positions suggests that the M2 segment forms a channel-lining loop originating and ending on the cytoplasmic side of the channel, with the ascending limb in an alpha-helical structure and the descending limb in an extended structure. A functionally critical asparagine (N-site) is positioned at the tip of the loop, and a cluster of hydrophilic residues of the descending limb, adjacent to the tip, forms the narrow constriction of the channel. An apparent asymmetric positioning of the NR1- and NR2-subunit N-site asparagines may account for their unequal role in Ca2+ permeability and Mg2+ block.     

Monotonic hypotheses in multiple group designs: A Monte Carlo study.

Monotonic hypotheses are predictions about the ordering of group population means. A journal survey revealed that the problem was very common and that there was little uniformity among researchers regarding the statistical test to use. Most of the approaches in the literature to detect both monotonic trend and nonmonotonicity were compared under varying population conditions in a Monte Carlo simulation. The results suggested that only rarely will sample means order the same as the corresponding population means, leaving the approaches most researchers used with far too little power. Trend tests had far greater power; the one recommended is the familiar linear trend test. However, used alone this test does not detect the presence of any instances of nonmonotonicity. Therefore, it should be used in combination with a technique that can detect such inversions, preferably the Sidák-corrected reversal test conducted with a very high α (.50). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An alfalfa rubisco small subunit homologue shares cis-acting elements with the regulatory sequences of the RbcS-3A gene from pea

A genomic clone of RbcS was isolated from an alfalfa (Medicago sativa L. cv. Apica) genomic library and characterized. Although this clone has structural features similar to a functional gene, the second exon is interrupted by a stop codon and thus is not fully translatable in the plant. Sequence analysis of the 5' and 3' noncoding regions of RbcSK-1A showed a high sequence homology to the flanking sequences of the RbcS-3A gene from pea. The regions of homology contain many important cis-regulatory elements shown to be essential for regulation of the RbcS-3A gene in pea. The promoter of this alfalfa rubisco clone was used in a translational fusion to test its ability to control the expression of the GUS reporter gene in an homologous nuclear background. High levels of GUS enzyme activity were recorded. These strong levels are comparable to some exceptionally high levels produced in other studies following the use of photosynthesis gene promoters in fusions with the GUS reporter gene.     

Development of hepatocellular carcinoma after clearance of hepatitis C virus with interferon therapy

Manifestations of fish allergy can include near-fatal anaphylactic reaction. In very sensitive patients, fish odors and cooking vapors may have some allergenic activity. We reported a case of life-threatening fish allergy in a girl of 39 months referred for three episodes of Quincke edema with wheezing, cyanosis and severe urticaria after fish consumption or inhalation. Reagins were found against codfish and direct skin prick test with fresh food (codfish) showed important local reaction. Strict avoidance of fish in the diet is usually the only recommended procedure. However, in this particular case, the life-threatening nature of the allergic reaction was the major consideration to perform a desensitization. The child was treated by RUSH immunotherapy using codfish extracts from BENCARD company, following the schedule for insect venom allergy described by Pharmacia. Immunotherapy was performed immediately after determination of the threshold of sensitivity by specific skin prick tests and intra-dermal injections. Desensitization was initiated with a 1/10 dilution of the cut-off solution and 5 subcutaneous injections were administered daily. When important local reactions were observed, additional doses were necessary to obtain tolerance. After the RUSH therapy, the child was submitted to uncooked codfish odors without any reaction. No reaction has been observed even when the child has accidentally eaten a little piece of codfish.     

Effect of chronic hypoxemia on the regulation of nitric-oxide synthase in the fetal sheep brain

We undertook a prospective study to determine the type and distribution of foot and ankle snowboarding injuries. Reports of 3213 snowboarding injuries were collected from 12 Colorado ski resorts between 1988 and 1995. Of these, 491 (15.3%) were ankle injuries and 58 (1.8%) were foot injuries. Ankle injuries included 216 (44%) fractures and 255 (52%) sprains. Thirty-three (57%) of the foot injuries were fractures and 16 (28%) were sprains. The remaining injuries were soft tissue injuries, contusions, or abrasions. There was no significant correlation between boot type (soft, hybrid, or hard) and overall foot or ankle injury rate. There were significantly fewer ankle sprains in patients wearing hybrid boots and fewer fractures of the lateral process of the talus in patients wearing soft boots. An unexpectedly high number of fractures of the lateral process of the talus were noted. These 74 fractures represented 2.3% of all snowboarding injuries, 15% of all ankle injuries, and 34% of the ankle fractures. Many of these fractures are not visible on plain radiographs and require computed tomography imaging to be diagnosed. Diagnosis of this fracture pattern is paramount; the physician should be very suspicious of anterolateral ankle pain in the snowboarder, where subtle fractures that may require surgical intervention can be confused with anterior talofibular ligament sprains.     

Solution structure of the sequence-specific HMG box of the lymphocyte transcriptional activator Sox-4

Two groups of HMG box proteins are distinguished. Proteins in the first group contain multiple HMG boxes, are non-sequence-specific, and recognize structural features as found in cruciform DNA and cross-over DNA. The abundant chromosomal protein HMG-1 belongs to this subgroup. Proteins in the second group carry a single HMG box with affinity for the minor groove of the heptamer motif AACAAAG or variations thereof. A solution structure for the non-sequence-specific C-terminal HMG box of HMG-1 has recently been proposed. Now, we report the solution structure of the sequence-specific HMG-box of the SRY-related protein Sox-4. NMR analysis demonstrated the presence of three alpha-helices (Val10-Gln22, Glu30-Leu41 and Phe50-Tyr65) connected by loop regions (Ser23-Ala49 and Leu42-Pro49). Helices I and II are positioned in an antiparallel mode and form one arm of the HMG box. Helix III is less rigid, makes an average angle of about 90 degrees with helices I and II, and constitutes the other arm of the molecule. As in HMG1B, the overall structure of the Sox-4 HMG box is L-shaped and is maintained by a cluster of conserved, mainly aromatic residues.