Synthesis and evaluation of 9-anilinothiazolo[5,4-b]quinoline derivatives as potential antitumorals

Five new 9-anilinothiazolo[5,4-b]quinoline derivatives (compounds 5, 7, 9, 10, 11) have been prepared. Some of the compounds were prepared by coupling properly substituted anilines to the novel compound 9-chloro-2-(methylthio)thiazolo[5,4-b]quinoline. Of these, compound 7 (9-anilino-2-[[2-(N,N-diethylamino)ethyl]amino]thiazolo[5,4-b]quinoline) showed the best cytotoxic activity in several cell lines. All compounds demonstrated DNA binding in nanomolar range. Compound 7 inhibited the (14)C-thymidine incorporation into DNA. Results indicate that these derivatives deserve more considerations as potential antitumoral drugs.     

Rating dysthymia: an assessment of the construct and content validity of the Cornell Dysthymia Rating Scale

BACKGROUND: Mason et al. developed the Cornell Dysthymia Rating Scale (CDRS), a 20-item clinician-rated inventory, and hypothesized that it may be superior to the commonly-used Hamilton Depression Rating Scale (HDRS) in assessing the symptoms of dysthymia, a form of chronic depression. The purpose of this study was to compare these instruments in an outpatient sample of dysthymic patients. METHOD: The CDRS and the HDRS and other inventories (including the Hopkins Symptom Check List (SCL)) were administered to 110 patients meeting DSM-IIIR diagnosis of dysthymia. RESULTS: There was a significant correlation between the CDRS and the HDRS at baseline and termination, indicating concurrent validity. Distributional statistics were compared for baseline and termination severity scores, showing that the CDRS has greater severity range scores than the HDRS. Furthermore, results of the DSM-IV Mood Disorders Field Trial suggest that the CDRS has better content validity than the HDRS when it comes to the dysthymic population. LIMITATIONS: The results are limited by the use of a homogeneous sample, the absence of observer ratings of divergent symptoms, and less than excellent validity of self-report divergent symptoms. CONCLUSIONS: Our results support the value of the CDRS in assessing symptoms of dysthymia.     

Nonuniformity of sarcomere shortenings in the isolated rat ventricular myocyte

By projecting the image of a single ventricular myocyte upon a linear image sensor, the striation pattern was analyzed during resting and contracting states. During rest, the individual cycle length (ICL) of the striation pattern varied from 1.8 to 2.0 microm within a given cell. ICL measured every 2 ms fluctuated approximately 0.05 microm around the mean. The variance of temporal fluctuations was decreased by chelating the extracellular Ca(2+) and increased by the Ca(2+) overload. Blocking the Ca(2+) release channels with 10 micromol/l ryanodine reversed this increase. In the power spectral density, an increase in the power occurred in the frequency range below 10 Hz. This increase should reflect overall kinetics of both intracellular Ca(2+) handling and responses of contractile filaments, because the same pattern was observed when spontaneous contractions occurred as well as when contractions were evoked by activating the L-type Ca(2+) channels. It is suggested that the temporal fluctuations of ICL in the resting state are caused by spontaneous Ca(2+) release from ryanodine receptors on the sarcoplasmic reticulum. Furthermore, under evoked contractions the shortenings of ICL were spatially inhomogeneous. These findings of nonuniform sarcomere shortenings are consistent with the temporal and spatial inhomogeneity of Ca(2+) transients.     

Cavoatrial bypass for occlusion of the inferior caval vein in a patient with Budd-Chiari syndrome

We report the case of a young man with Budd-Chiari syndrome and occlusion of the inferior caval vein. Peripheral edema was his predominant complaint. Symptoms of portal hypertension were lacking, indicating membranotomy and not portosystemic shunting as the treatment of choice. At operation, membranotomy was not feasible, and a cavoatrial bypass using a 22 mm Gore-Tex graft was placed instead. Shortly after the operation the peripheral edema vanished, diuretic treatment could be withdrawn, and liver function improved. Eighteen months later the bypass remains patent, edema is absent, and liver function is stable. We conclude that cavoatrial bypass is a therapeutic option in patients with occlusion of the inferior vena cava with no clinical symptoms of portal hypertension if transcardiac membranotomy is not feasible.     

Keratometric astigmatism after suture removal in penetrating keratoplasty: double running versus single running suture techniques

BACKGROUND AND OBJECTIVE: To compare astigmatism after suture removal in a retrospective sequential series of patients who had penetrating keratoplasty with either a double running suture technique or an adjustable single running suture technique. During the first year postkeratoplasty, when sutures were in place, the latter technique had produced less astigmatism. MATERIALS AND METHODS: Keratometry and keratometric astigmatism were measured before and after suture removal. We compared these variables in 30 grafts with the double running suture technique to the same variables in 24 grafts with the single running suture technique. RESULTS: The final portion of the double running suture was removed 408 +/- 177 (mean +/- SD) days after keratoplasty, whereas the single running suture was removed 611 +/- 224 days after keratoplasty (P<0.001). After suture removal, there was no difference between the double running and single running groups in either mean keratometry [46.5 +/- 1.8 diopters (D) versus 45.6 +/- 2.0 D, P=0.09, minimum detectable difference (MDD)=1.5D] or mean astigmatism (4.6 +/- 2.7 D versus 5.2 +/- 3.2D, P=0.72, MDD=2.3). CONCLUSION: In this consecutive series of corneal transplants performed by one surgeon, the results suggest no difference in astigmatism between the two suturing techniques after all sutures have been removed.     

Lack of association between the kinetics of human cytomegalovirus (HCMV) glycoprotein B (gB)-specific and neutralizing serum antibodies and development or recovery from HCMV active infection in patients undergoing allogeneic stem cell transplant

The kinetics of the gB-specific and neutralizing antibody responses to human cytomegalovirus (HCMV) were analyzed in 26 allogeneic stem-cell transplant recipients who either did (n = 20) or did not (n = 6) develop asymptomatic HCMV active infection during the study period. Antibody response profiles varied widely among individuals in both groups, irrespective of whether HCMV active infection did or did not occur. Development of HCMV active infection was not preceded by a decline in functional serum antibody levels. Neither the absence nor the presence of HCMV active infection correlated with either high or low serum levels of gB-specific and neutralizing antibodies, respectively. In most patients, episodes of HCMV replication were not followed by a marked increment in functional serum antibody titers. Therefore, resolution of an ongoing HCMV active infection was not associated with a vigorous antibody response to viral replication. In addition, this study supports previous data indicating that passive transfer of human immunoglobulins may result in an increment in gB-specific and neutralizing serum antibody levels, the magnitude of which varies among recipients; however, both patients with and without measurable increments in serum antibody levels developed HCMV active infections with comparable frequency.     

Recurrent polychondritis: apropos of a case

We present a case of relapsing polychondritis which presented as hypoacusis and showed several peculiarities. The initial diagnosis was serous otitis. After a more careful study we found certain details which made us suspect a relapsing polychondritis. The diagnosis was confirmed by a biopsy of the nasal cartilage and a detailed systemic study was performed. As distinctive characteristics we found a mixed hypoacusis, in which the sensorineural component was partially recovered following corticoid treatment.     

Germline mutations in the CCM1 gene, encoding Krit1, cause cerebral cavernous malformations

Mutations in the Kritl gene have been recently discovered as the cause of hereditary cerebral cavernous angioma. We sought the possibility that de novo, noninherited mutations of Kritl also cause cavernous angioma. A patient with two cerebral malformations carries a heterozygous deletion of two base pairs (741delTC) in exon VI of the Kritl gene. The deletion initiates a frameshift mutation that, 23 amino acids downstream, encodes a TAA stop triplet replacing a CAT triplet of histidine at exon VII (H271X). Magnetic resonance images of the parents were normal, neither parent carries the 741delTC mutation, and both bear the wild-type sequence of exon VI. These findings document a de novo germline mutation in Kritl gene that causes cerebral cavernous malformations.