Intravenous cidofovir treatment for recalcitrant warts in the setting of a patient with myelodysplastic syndrome

Cidofovir is an acyclic nucleoside phosphonate with broad-spectrum activity against DNA viruses, including human papilloma virus (HPV). However, data on the efficacy of cidofovir in an immunosuppressive setting remain contradictory. We report for the first time on the promotion of the healing of recalcitrant warts in a patient with myelodysplastic syndrome with intravenous cidofovir treatment.     

Digital radiography of subtle pulmonary abnormalities: an ROC study of the effect of pixel size on observer performance

Forty conventional radiographs with examples of mild interstitial infiltrates and subtle pneumothoraces and 40 normal studies of the chest were selected and digitized, with pixel sizes of 1.0, 0.5, 0.2, and 0.1 mm. Observer performance tests were carried out using receiver operating characteristic analysis. Conventional radiographs and digitized images were compared. The results indicate that, in such cases, diagnostic accuracy increases significantly as the pixel size is reduced, at least to the 0.1-mm level. We conclude that, for digital systems using screen-film or similar image receptors, use of a pixel size substantially larger than 0.1 mm may result in some loss of diagnostic accuracy.     

An Inbred Epilepsy-Prone Substrain of BALB/c Mice Shows Absence of the Corpus Callosum, an Abnormal Projection to the Basal Forebrain, and Bilateral Projections to the Thalamus

BALB/c mice lack a corpus callosum in about 11% of the population.Two inbred substrains of BALB/c mice, epilepsy-prone (EP) andepilepsy-resistant (ER), have been examined to determine whetherthese substrains differ in regard to corpus callosum morphology.Further, this study addressed the issue of whether misroutedcortical axons form an aberrant pathway instead of the corpuscallosum. Initial studies that examined fresh brain tissue ofadult animals revealed normal corpora callosa in all ER micebut deficient or absent corpora callosa in all EP mice. Subsequently,Dil crystals were placed in the motor cortices of aldehyde-fixedbrains of 2-week-old animals to investigate cortical projectionsin both inbred substrains of mice. Fluorescent microscopy revealedthat all of the ER animals had normal corpora callosa, whereasall EP animals exhibited either reduced corpora callosa (partiallycallosal) or an absence (acallosal) of this structure. Bothacallosal and partially callosal EP mice displayed an extensive,aberrant projection to the basal forebrain as well as bilateralprojections to midline and intralaminar thalamic nuclei. Thefibers projecting to the basal forebrain arose from the cortex,coursed toward the midline before turning ventrally along themidline, and appeared to terminate in the medial septal nucleusand the nucleus of the diagonal band. ER animals lacked thisaberrant cortical projection to the basal forebrain. Electronmicroscopic results obtained from EP mice indicated that labeledaxons in this aberrant pathway formed axosomatic, axodendritic,and axospinous synapses with the neurons in the medial septal/diagonalband complex. The function of the aberrant projection to thebasal forebrain remains unknown but it may provide an abnormalexcitatory input to a region that provides cholinergic and GABAergicinput to the cerebral cortex and hippocampus. The additionalprojections to midline and contralateral intralaminar thalamicnuclei in EP mice may function to intensify the synchronizationof bilateral discharges.     

Air accidents, pilot experience, and disease-related inflight sudden incapacitation

The epidemiology of sudden death, the etiology of inflight sudden incapacitation, and the influence of pilot age and experience on air accident rates are reviewed in order to determine the aeromedical emphasis needed to minimize accidents. Sudden deaths in men over age 35 are nearly all due to coronary artery disease, whereas in those under 35 years they are mostly due to hypertrophic cardiomyopathy. The incidence of fatal accidents from human error is, however, far greater than that from physical illness. Since inexperienced pilots have a 2-3 times increased incidence of mishaps due to pilot error, the estimated risk of disease related in-flight sudden incapacitation should be balanced by consideration of pilot experience. Therefore, it may be preferable to grant waivers to experienced pilots with an increased incidence of disease-related inflight sudden incapacitation than to replace them with novices. We conclude that overly strict medical criteria may paradoxically increase accident rates.     

Frequent ongoing T-cell receptor rearrangements in childhood B- precursor acute lymphoblastic leukemia: implications for monitoring minimal residual disease

Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL.     

Picotamide inhibition of excess in vitro thromboxane B2 release by colorectal mucosa in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease is associated with increased mucosal release of eicosanoids. Among these, thromboxane A2 has been proposed as a possible inflammatory mediator; its suppression may be a useful therapeutic option. METHODS: Using a tissue incubation technique, we compared release of immunoreactive thromboxane B2 by colonic biopsies from patients with ulcerative colitis, Crohn's disease and controls, and assessed the inhibitory effect of picotamide, a thromboxane synthesis inhibitor-receptor antagonist, which has been widely used in Italy for management of ischaemic heart and cerebrovascular disease. RESULTS: Increased amounts of thromboxane B2 were released from biopsies from patients with active ulcerative colitis (median 238 pg/20 min/mg wet weight (interquartile range 147- 325), n = 12) and active Crohn's disease (252 (174-450), 6) compared with those from patients with quiescent ulcerative colitis (95 (61- 140), 12) or Crohn's disease (105 (57-201), 13), or controls (136 (64- 206), 8). Incubation with picotamide at concentrations between 100 microM and 1 mM reduced thromboxane B2 release (IC50 890 microM). CONCLUSION: Since increased thromboxane A2 production may have pathogenetic importance, thromboxane synthesis inhibitor-receptor antagonists such as picotamide merit therapeutic trial in the management of inflammatory bowel disease.