Superimposed pressure oscillations: An alternative to treat airway hyperresponsiveness in an acute sensitized airways mouse model.

The main driving mechanism during an asthma attack is the hyper-constrictions of airway smooth muscle (ASM), which reduces the airway lumen and makes normal breathing difficult. In spite of some noticeable side effects, bronchodilator drugs such as salbutamol are used to alleviate these symptoms by inducing temporary relaxation of the contracted ASM. In vitro studies have shown that mechanical oscillation can induce relaxation in isolated contracted ASM obtained from healthy subjects but not from asthmatics. To date, little is known about in vivo ASM behaviours, in particular in asthmatic subjects. This in vivo study aims at determining the effect of various superimposed pressure oscillation (SIPO) patterns (different to those occurring during normal breathing) on sensitized airways during an ACh challenge (mimicking an asthmatic attack) and comparing it with the effect of a widely studied broncho-relaxant drug, Isoproterenol (ISO). The study shows that superimposed pressure oscillation in the range of 5-15Hz induces approximately 50% relaxation on pre-constricted sensitized airways in vivo; however, this behaviour was not observed at 20Hz. Our finding suggests that mechanical oscillation, particularly SIPO, may act as a bronchodilator and achieve ASM relaxation.

Posterior longitudinal ligament resection or preservation in anterior cervical decompression surgery.

We reviewed the literature to determine differences in clinical outcomes for the removal or preservation of the posterior longitudinal ligament (PLL) in anterior cervical discectomy and fusion (ACDF). The outcomes are surgeon and case-dependent for both practices. A literature review was performed in PubMed from the years 1960 to 2014 to identify studies describing surgeries where the PLL was removed or preserved during ACDF. Searches were performed using Medical Subject Headings (MeSH) and references included in the reviewed articles were also considered. Additionally we searched recent articles that cited those from the original search. The search yielded 79 articles and 115 pertinent citations. These 194 articles were reviewed for specific discussions of PLL resection or preservation. Four articles containing 122 patients were included in the final analysis. In 69 patients the PLL was removed and in 53 the PLL was preserved. Both groups improved in clinical scores during follow up. One patient in the PLL removal group had a cerebrospinal fluid leak. MRI and correlative outcome data suggest that a non-ossified PLL itself does not contribute to significant cord compression. Postoperative MRI of patients with the PLL removed showed a larger spinal cord diameter. Resection of the PLL is safe and common in ACDF surgery but there does not appear to be a demonstrable clinical difference in patients where it is resected. The ultimate decision is likely surgeon and case-dependent. Randomized trials could further determine the importance of PLL removal in ACDF treated patients.

Unconditional inferences on the difference of two proportions in cross-sectional studies.

In order to analyse a 2 x 2 table it is usual to perform inferences (hypothesis test or interval of confidence) on the difference d = p2 - p1 between two independent proportions. To this end it has been customary to adopt the Fisher conditional method, but nowadays the unconditional method of Barnard is increasingly adopted. However, all the present unconditional inferences are based on a double-binomial model. This article performs these inferences - exact and asymptotic - under a multinomial model, which is the appropriate one when the data proceed from a cross-sectional survey. At http://www.ugr.es/-bioest/SG_ASO.EXE there is a program for performing the said unconditional tests that may be copied.

Bone marrow transplantation in dogs after radio-ablation with a new Ho-166 amino phosphonic acid bone-seeking agent (DOTMP).

beta-emitting 166Ho (t1/2 = 26.78 hours, E(beta)max = 1.8 MeV) complexed with the phosphonic acid chelator, 1,4,7,10 tetraazacyclododecane-1,4,7,10-tetra(methylene phosphonic acid) (DOTMP) at a ligand-to-metal ratio of 1.5:1 binds to bone. This radioactive complex is a marrow-ablating radiopharmaceutical that appears useful for preparation of bone marrow (BM) transplant recipients without the morbidity usually associated with total body irradiation preparatory regimens. We have found with seven splenectomized young adult beagle dogs that a 166Ho radiopharmaceutical dosage of 370 MBq/kg body weight provides an initial skeletal radioactivity burden of at least 1.5 GBq/kg skeleton and results in complete ablation of hematopoietic marrow cell populations within 7 days. The beta particle flux distribution in BM-forming skeletal tissue is not uniform. Red marrow radiation doses varied from 30 to 115 Gy as estimated by direct radioassay and autoradiographic analyses of both bone biopsies and postmortem samples; the median value of 61 Gy agreed with our theoretical expectations. In vivo radioactivity distribution was evaluated with nuclear imaging methods. Apparently, normal hematopoiesis was restored in three dogs with autologous BM transplants performed 5 to 6 days after administration of the marrow ablative radiopharmaceutical, 166Ho-DOTMP. BM biopsies at 7 to 10 months posttransplantation indicate continued normal hematopoietic activity.

Experimental validation of radiopharmaceutical absorbed dose to mineralized bone tissue.

Therapeutic and palliative uses of bone-seeking radiopharmaceuticals are undergoing clinical trials for human subjects. Radiation dosimetry for these applications is based on the Medical Internal Radiation Dosimetry (MIRD) schema. An experimental method for dosimetry of bone tissue based on electron paramagnetic resonance (EPR) spectrometry is described. Preliminary results for beagle bone exposed to radiopharmaceuticals under clinical conditions have indicated that the EPR dose measurements give approximately the calculated dose, but suggest that the dose distribution may be non-uniform.

Specific IgE antibodies to vespids in the course of immunotherapy with Vespula germanica administered to patients sensitized to Polistes dominulus.

Sera from a group of 12 patients with anaphylactic reactions to vespids were studied. Field observations and RAST values suggested that the offending insect was Polistes dominulus (PD). Specific IgE antibodies to PD appeared in all cases and to Vespula germanica (VG) in nine. Absorption studies in these basal sera showed that IgE antibodies to VG were due to cross-reactivity with PD. The RAST value to both venoms was higher after immunotherapy (IT) in six cases. IgE antibodies increased to determinants common to both vespids, and in 41% of the cases to specific epitopes of VG venom allergens not initially detected in the basal sera. In one case antibodies increased only to VG without a corresponding rise to PD. These results indicate that if the correct venom to which the individuals are sensitized is not administered IgE antibodies may appear which were not initially detected in the patients' sera. The levels of these antibodies declined during the course of IT.

Allergy to penicillin with good tolerance to other penicillins; study of the incidence in subjects allergic to beta-lactams.

Two hundred and eighty-eight subjects with a history of allergy to penicillin were studied for objective proof of their allergy. On the basis of skin tests, specific IgE antibody measurements and direct challenge tests. 64 patients (22%) were shown objectively to be allergic to one or more penicillins. The following tests were carried out: skin tests to benzyl-penicilloyl poly-L-lysine (BPO-PLL), minor determinant mixture (MDM), amoxycillin (AX) and ampicillin (AMP), in-vitro IgE antibody measurement to benzyl-penicilloyl (BPO) and AX and challenge with benzylpenicillin (BP), phenoxy-methyl-penicillin (PV) and amoxycillin. Forty-four cases were found to respond to benzyl or phenoxymethyl-penicillin, however, 20 were shown to be sensitive to amoxycillin and unresponsive to tests with other penicillins. The contribution that any individual test gave for establishing the diagnosis was 21.8% for skin testing with BPO-PLL, 9.3% with MDM and 12.5% with AX. Nine point three per cent were RAST positive to BPO and 1.5% to AX; 7.8% developed a positive response after challenge to BP, 7.8% to PV and 14% to AX. In 16% of the 64 positive cases more than one test was found to be positive. The challenge tests suggested that not all the penicillin-sensitive subjects had IgE-mediated reactions implying other immunological mechanisms. These results clearly demonstrate the importance of side chain-specific diagnostic reagents and challenge tests. Thirty-one per cent of the positive group or 6.9% of the total group would have been missed in this study using benzyl or phenoxymethyl-penicillin diagnostic reagents alone.

Cross-reactivity between penicillins and cephalosporins: clinical and immunologic studies.

Nineteen well-characterized penicillin-allergic patients were investigated for their sensitivity to cephalosporins containing potentially cross-reactive side chains. All patients were administered cephamandole parenterally and, if this was tolerated, a course of oral cephaloridine was administered. Only two patients responded to the cephamandole; none of the remaining patients reacted to cephaloridine. Benzylpenicilloyl RAST-inhibition studies with sera from three subjects who had not reacted to the cephalosporins demonstrated that cephamandole linked to proteins was capable of recognizing benzylpenicilloyl-specific IgE antibody. It is concluded that consideration of side chain structures can help to predict possible cross-reactions between penicillins and cephalosporins, but carefully controlled challenge tests are advisable before penicillin-allergic patients are treated with cephalosporins. In relation to cross-reacting potential, in vitro experimental studies are difficult to interpret and may in some circumstances overestimate the risk.

Targetry and radiochemical methods for the simultaneous cyclotron production of no-carrier-added radiopharmaceutical-quality 100Pd, 97Ru and 101mRh.

Target-dissolution and radiochemical methods were investigated to optimize the simultaneous production of radiopharmaceutical-quality, no-carrier-added (NCA) 3.63-d 100Pd, 2.88-d 97Ru and 4.26-d 101mRh. These radionuclides have potential as radiotracer labels and/or as short-range dose emitters for use with specific-function radiopharmaceuticals being investigated for radioimmunotherapy applications. Metallic Rh (100% 103Rh) and RhCl3 X 3H2O were used as target materials. After bombardment with high energy protons these targets were subjected to a combination of procedures (i.e. electrolytic dissolution, ion-exchange, and solvent extraction) in order to separate the desired radionuclides. The use of a single cyclotron target in combination with several radiochemical processes were investigated to simultaneously produce these radionuclides in high-specific activities and radiochemical forms suitable for radiopharmaceutical syntheses.