Cetirizine dihydrochloride interaction with some diclofenac complexes.

IR, 1H NMR and mass spectrometric studies showed that cetirizine dihydrochloride interacted strongly with diclofenac sodium, even when the latter was metal bound, forming high molecular weight stable adducts. These new formations were unaffected by the possible steric constraints that may exist because of coordination yet did not have the power to break the formed coordinate bonds. The formed ionic bond took place between the carbonyl ion of diclofenac and the positively charged piperazine ring of cetirizine, forming a ternary compound in the case of the divalent metal clusters (Ca{(dic)2.2H2O}, Mg{(dic)2.2H2O}, Zn{(dic)2.2H2O}) and a quaternary one with the trivalent iron cluster (Fe{dic}3.3H2O). IR bands assigned to nuNH, deltaNH and nuC-N were shifted to lower frequency values in the spectra of the complexes; thus showing that coordination took place at the NH of the diphenylamine. TG and elemental analysis confirmed these results.     

Autoantibodies and drug-or metabolite-dependent antibodies in patients with diclofenac-induced immune haemolysis

Two patients with acute immune haemolytic anaemia caused by diclofenac are described. Both patients had developed IgG drug-independent autoantibodies and drug-dependent antibodies. The drug-dependent antibodies in one patient reacted with red blood cells (RBC) only in the presence of urine from patients receiving diclofenac (ex vivo antigen) but not in the presence of the drug itself or its known metabolites. This antibody appeared to recognize a trace metabolite which has not yet been identified. The drug-dependent antibodies in the second patient reacted with RBC in the presence of urine as ex vivo antigen as well as in the presence of the drug itself and its main metabolites. Incorrect diagnosis of such cases often is due to the occurrence of autoantibodies and/or unusual drug metabolism and excretion.     

Candida albicans osteomyelitis of the spine: progressive clinical and radiological features and surgical management in three cases

Candida albicans vertebral osteomyelitis is rare. Three cases are presented. Without antifungal treatment, they developed spinal collapse and neurological deterioration within 3–6 months from the onset of symptoms. There was a delay of 4.5 and 7.5 months between the onset of symptoms and surgery. All patients were managed with surgical debridement and reconstruction and 12-week fluconazole treatment. The neurological deficits resolved completely. The infection has not recurred clinically or radiologically at 5–6 years follow-up. Although rare, Candida should be suspected as a causative pathogen in cases of spinal osteomyelitis. Without treatment the disease is progressive. As soon as osteomyelitis is suspected, investigations with MRI and percutaneous biopsy should be performed followed by medical therapy. This may prevent the need for surgery. However, if vertebral collapse and spinal cord compression occurs, surgical debridement, fusion and stabilisation combined with antifungal medications can successfully eradicate the infection and resolve the neurological deficits.     

Feasibility of cranio-spinal axis radiation with the Hi-Art tomotherapy system.

BACKGROUND AND PURPOSE: Helical tomotherapy can eliminate the need for junction lines. The goal of this study is to evaluate tomotherapy in the delivery of CSA radiation and measurement of plan quality using physical parameters in comparing conventional (CSA-RT) and helical tomotherapy (CSA-TOMO) plans. PATIENTS AND METHODS: CSA-TOMO and CSA-RT plans were created for dosimetric comparison. Integral dose values were calculated. The ratios D50% (dose received by 50% of the organ at risk's volume) and D10% (dose received by 10% of the organ at risk's volume) were calculated representing large volumes and small volumes of organs at risk receiving significant dose. RESULTS: When considering D50% and D10%, CSA-TOMO has a dosimetric advantage over CSA-RT for most organs at risk. The body integral dose was higher for the CSA-TOMO plan by approximately 6.5%. CONCLUSIONS: Tomotherapy is a feasible alternative for treatment of CSA. Analysis shows that tomotherapy improves dose ratios over conventional radiation for most organs at risk. The impact of a small increase in whole body integral dose is unknown. Long-term follow-up will be needed to answer this question as others have argued of the possibility of increased risk of secondary malignancies due to delivery of radiotherapy with IMRT.     

Long‐standing ulcerative colitis complicated by right subclavian artery occlusion and upper limbs arteriolitis with digital ischemia

A 48‐year‐old male patient with long‐standing ulcerative colitis since February 2001 which was diagnosed by endoscopy, developed acute digital ischemia affecting both hands with fixed colour changes in the left index finger which was followed shortly by digital ulceration. Magnetic resonance angiography (MRA) of both upper limbs showed evidence of vasculitis affecting digital arterioles on both sided and right subclavian occlusion. The patient received pulse methylprednisolone followed by cyclophosphamide pulse therapy, the latter continuing on a monthly basis for 6 months with appreciable improvement and remission of the vasculitic process; follow‐up MRA showed reperfusion of the previously occluded subcalvian artery. To the authors’ knowledge vasculitis complicating the course of ulcerative colitis is a rare association and is only sporadically reported in the literature. This rare entity should be diagnosed early and aggressively treated; MRA is a very promising diagnostic tool that is suitable for both diagnosis and follow‐up of patients with this rare entity.     

Mechanisms of Tolerance Induced by Donor-Specific Transfusion and ICOS-B7h Blockade in a Model of CD4+ T-Cell-Mediated Allograft Rejection

The inducible co-stimulatory molecule (ICOS) has been shown to play a critical role in T-cell activation and differentiation, and the regulation of alloimmune responses in vivo. Using an MHC class II mismatched model of CD4(+) T-cell-mediated rejection, we found that treatment of mice with DST and ICOS-B7h blockade induced long-term skin allograft survival and donor-specific transplantation tolerance. ICOS blockade, either during antigen priming or during the effector phase, previously shown to alter the outcome of the immune response, had a similar effect on graft survival. DST and anti-B7h mAb reduced the frequency of IFN-gamma-producing allospecific cells but did not produce deviation to a T(H)2 phenotype. In an adoptive transfer model using ABM TCR transgenic mice directly reactive to I-A(bm12), DST and anti-B7h mAb reduced the number of allospecific CD4(+) T cells and increased CD4(+) T-cell apoptosis. These data demonstrate that DST and anti-B7h mAb induces transplantation tolerance to MHC class II mismatched skin grafts by a reduction of the alloreactive clone size that is, at least in part, dependent on apoptosis of host alloantigen-specific CD4(+) T cells.     

Fatal Dieulafoy's type ulcer in a case of gastric AL-amyloidosis

Dieulafoy's ulcer is a particular form of gastric ulcer confined to a persistent caliber artery and may lead to severe hemorrhage. We report a case of fatal gastric bleeding in a woman with benign biclonal gammapathy. Autopsy found a typical Dieulafoy's ulcer centered by a persistent caliber artery which wall was thickened by AL-amyloid deposits. Amyloidosis involved the gastric wall, but also middle caliber arteries of the liver, the lung, the pancreas, the kidney and the myocardium. AL-amyloidosis is a rare and late complication of monoclonal gammapathy and may be asymptomatic. Pathogenesis of Dieulafoy's ulcer remains unclear. In our case, local ischemia may have facilitated gastric ulceration, and amyloid deposits may have contributed to arterial rupture.     

Characterisation of electrocardiogram signals based on blind source separation

Blind source separation assumes that the acquired signal is composed of a weighted sum of a number of basic components corresponding to a number of limited sources. This work poses the problem of ECG signal diagnosis in the form of a blind source separation problem. In particular, a large number of ECG signals undergo two of the most commonly used blind source separation techniques, namely, principal component analysis (PCA) and independent component analysis (ICA), so that the basic components underlying this complex signal can be identified. Given that such techniques are sensitive to signal shift, a simple transformation is used that computes the magnitude of the Fourier transformation of ECG signals. This allows the phase components corresponding to such shifts to be removed. Using the magnitude of the projection of a given ECG signal onto these basic components as features, it was shown that accurate arrhythmia detection and classification were possible. The proposed strategies were applied to a large number of independent 3s intervals of ECG signals consisting of 320 training samples and 160 test samples from the MIT-BIH database. The samples equally represent five different ECG signal types, including normal, ventricular couplet, ventricular tachycardia, ventricular bigeminy and ventricular fibrillation. The intervals analysed were windowed using either a rectangular or a Hamming window. The methods demonstrated a detection rate of sensitivity 98% at specificity of 100% using nearest neighbour classification of features from ICA and a rectangular window. Lower classification rates were obtained using the same classifier with features from either PCA or ICA and a rectangular window. The results demonstrate the potential of the new method for clinical use.     

IL-4 and IL-10 modulate autoimmune haemolytic anaemia in NZB mice

New Zealand Black (NZB) mice spontaneously develop autoimmune haemolytic anaemia (AIHA). Here the effect of injecting NZB mice with plasmids encoding IL-4 (pIL-4) or IL-10 (pIL-10) on NZB disease was tested. Both constructs delayed the development of anaemia as judged by increased haematocrit values as compared with controls, but neither altered the IgG1 to IgG2 red blood cell (RBC) bound autoantibody levels. The increased haematocrit value was associated temporally with increased RBC bound IgG in NZB mice treated with pIL-10, but not pIL-4. By contrast, up-regulation of splenic macrophage FcgammaRIIb2 mRNA was associated temporally with increased haematocrit values in NZB mice given pIL-4. However, no such increase occurred in NZB mice that inhaled a peptide containing a dominant T-cell epitope, although this treatment is known to bias the autoimmune response towards Th2 and to reduce the severity of anaemia. It is considered that IL-4 treatment, in part, ameliorates NZB anaemia by increasing the expression of the inhibitory FcgammaRIIb2 and thereby reducing the capacity of splenic macrophages to phagocytose autoantibody coated RBC, but that this mechanism does not explain the beneficial effects of the inhaled peptide.