Human heterophil antibodies against rat erythrocytes. I. Changes after renal transplantation

A significant increase in titre of human heterophil antibodies against rat erythrocytes was demonstrated in eighteen of twenty-eight patients after renal transplantation. Although this rise in titre preceded an acute rejection episode in the renal graft in some instances, it is considered that this relationship was coincidental. There is no relationship between the numbers of such rejection episodes or the degree of incompatibility for HL-A antigens between donor and recipient and the titres of heterophil antibodies after transplantation.     

Prenatal magnetic resonance imaging in Gomez-Lopez-Hernandez syndrome and review of the literature

Gomez-Lopez-Hernandez syndrome, or cerebello-trigeminal-dermal dysplasia (OMIM#601853), is a rare syndrome comprising cerebellar abnormalities, parieto-occipital alopecia, trigeminal nerve anesthesia, intellectual impairment, craniosynostosis, short stature, and craniofacial anomalies. It has been reported in ten patients, five of whom are Brazilian. Rhombencephalosynapsis is a rare sporadic cerebellar anomaly comprising fusion of the cerebellar hemispheres with agenesis of the cerebellar vermis. Rhombencephalosynapsis is a constant feature of Gomez-Lopez-Hernandez syndrome. We present the clinical and imaging findings of a Caucasian male infant with Gomez-Lopez-Hernandez syndrome. Rhombencephalosynapsis was diagnosed with fetal magnetic resonance imaging (MRI) after an abnormally shaped small cerebellum was detected by antenatal ultrasound (US). Gomez-Lopez-Hernandez syndrome was diagnosed at age 6 weeks when parietal alopecia was noted. Prenatal imaging studies of Gomez-Lopez-Hernandez syndrome have not been published before. When rhombencephalosynapsis is diagnosed prenatally, the clinical features of Gomez-Lopez-Hernandez syndrome should be sought at postnatal review. Gomez-Lopez-Hernandez syndrome and isolated rhombencephalosynapsis may have a common etiology.     

Phase I study of vorinostat with gefitinib in BIM deletion polymorphism/epidermal growth factor receptor mutation double‐positive lung cancer

Patients with epidermal growth factor receptor (EGFR)‐mutated non‐small cell lung cancer (NSCLC) harboring BIM deletion polymorphism (BIM deletion) have poor responses to EGFR TKI. Mechanistically, the BIM deletion induces preferential splicing of the non‐functional exon 3‐containing isoform over the functional exon 4‐containing isoform, impairing TKI‐induced, BIM‐dependent apoptosis. Histone deacetylase inhibitor, vorinostat, resensitizes BIM deletion‐containing NSCLC cells to EGFR‐TKI. In the present study, we determined the safety of vorinostat‐gefitinib combination and evaluated pharmacodynamic biomarkers of vorinostat activity. Patients with EGFR‐mutated NSCLC with the BIM deletion, pretreated with EGFR‐TKI and chemotherapy, were recruited. Vorinostat (200, 300, 400 mg) was given daily on days 1‐7, and gefitinib 250 mg was given daily on days 1‐14. Vorinostat doses were escalated based on a conventional 3 + 3 design. Pharmacodynamic markers were measured using PBMC collected at baseline and 4 hours after vorinostat dose on day 2 in cycle 1. No dose‐limiting toxicities (DLT) were observed in 12 patients. We determined 400 mg vorinostat as the recommended phase II dose (RP2D). Median progression‐free survival was 5.2 months (95% CI: 1.4‐15.7). Disease control rate at 6 weeks was 83.3% (10/12). Vorinostat preferentially induced BIM mRNA‐containing exon 4 over mRNA‐containing exon 3, acetylated histone H3 protein, and proapoptotic BIM_EL protein in 11/11, 10/11, and 5/11 patients, respectively. These data indicate that RP2D was 400 mg vorinostat combined with gefitinib in BIM deletion/EGFR mutation double‐positive NSCLC. BIM mRNA exon 3/exon 4 ratio in PBMC may be a useful pharmacodynamic marker for treatment.     

NSAIDS-induced anaphylaxis precipitating acute coronary vasospasm

We report a case of NSAID-induced anaphylaxis precipitating coronary artery vasospasm leading to myocardial infarction in the presence of normal coronaries. Furthermore, we have also discussed the possible mechanisms for this. Attending clinicians should be aware of this potential complication when treating anaphylaxis, especially in patients with known or presumed coronary artery disease.     

Beta-adrenoceptor and post-receptor components show different rates of desensitization to desipramine

Both 3-day and 15-day desipramine treatments (10 mg/kg, once daily) significantly reduced beta 1- but not beta 2-adrenoceptor and isoproterenol-stimulated adenylyl cyclase activities in rat cortical, hippocampal and amygdaloid membrane preparations. In contrast, 15-day but not 3-day desipramine treatment resulted in a significant reduction in NaF-, GppNHp- and forskolin-stimulated adenylyl cyclase activity. The results suggest that post-beta-adrenoceptor component desensitization occurs more slowly than receptor downregulation in response to desipramine.     

Anti-emetic effect of high-dose metoclopramide vs alizapride--a randomised crossover study.

A randomised double-blind crossover study was undertaken to compare the anti-emetic efficacy of alizapride against high dose metoclopramide. A total of 32 patients on cisplatin were randomised to receive either high dose metoclopramide (7 mg kg-1 day-1) or alizapride (5 mg kg-1 day-1). Anti-emetic responses in terms of control of vomiting episodes were similar in both regimens (59%). However, patients showed a statistically significant preference for high dose metoclopramide (P = 0.02). Side effects of both regimens were minimal. We conclude that alizapride is not superior to high dose metoclopramide in controlling cisplatin induced vomiting.     

Prediction of thrombus-related mechanical prosthetic valve dysfunction using transesophageal echocardiography

Identification of thrombus-related mechanical prosthetic valve dysfunction (MPVD) has important therapeutic implications. We sought to develop an algorithm, combining clinical and echocardiographic parameters, for prediction of thrombus-related MPVD in a series of 53 patients (24 men, age 52 +/- 16 years) who had intraoperative diagnosis of thrombus or pannus from 1992 to 1997. Clinical and echocardiographic parameters were analyzed to identify predictors of thrombus and pannus. Prevalence of thrombus and diagnostic yields relative to the number of predictors were determined. There were 22 patients with thrombus, 19 patients with pannus, and 12 patients with both. Forty-two of 53 masses were visualized using transesophageal echocardiography (TEE), including 29 of 34 thrombi or both thrombi and panni and 13 of 19 isolated panni. Predictors of thrombus or mixed presentation include mobile mass (p = 0.009), attachment to occluder (p = 0.02), elevated gradients (p = 0.04), and an international normalized ratio of < or = 2.5 (p = 0.03). All 34 patients with thrombus or mixed presentation had > or = 1 predictor. The prevalence of thrombus in the presence of < or = 1, 2, and > or = 3 predictors is 14%, 69%, and 91%, respectively. Thus, TEE is sensitive in the identification of abnormal mass in the setting of MPVD. An algorithm based on clinical and transesophageal echocardiographic predictors may be useful to estimate the likelihood of thrombus in the setting of MPVD. In the presence of > or = 3 predictors, the probability of thrombus is high.     

Assessment of global and regional left ventricular function using 64-slice multislice computed tomography and 2D echocardiography: a comparison with cardiac magnetic resonance

OBJECTIVES: To compare the assessment of global and regional left ventricular (LV) function using 64-slice multislice computed tomography (MSCT), 2D echocardiography (2DE) and cardiac magnetic resonance (CMR). METHODS: Thirty-two consecutive patients (mean age, 56.5+/-9.7 years) referred for evaluation of coronary artery using 64-slice MSCT also underwent 2DE and CMR within 48h. The global left ventricular function which include left ventricular ejection fraction (LVEF), left ventricular end diastolic volume (LVdV) and left ventricular end systolic volume (LVsV) were determine using the three modalities. Regional wall motion (RWM) was assessed visually in all three modalities. The CMR served as the gold standard for the comparison between 64-slice MSCT with CMR and 2DE with CMR. Statistical analysis included Pearson correlation coefficient, Bland-Altman plots and kappa-statistics. RESULTS: The 64-slice MSCT agreed well with CMR for assessment of LVEF (r=0.92; p<0.0001), LVdV (r=0.98; p<0.0001) and LVsV (r=0.98; p<0.0001). In comparison with 64-slice MSCT, 2DE showed moderate correlation with CMR for the assessment of LVEF (r=0.84; p<0.0001), LVdV (r=0.83; p<0.0001) and LVsV (r=0.80; p<0.0001). However in RWM analysis, 2DE showed better accuracy than 64-slice MSCT (94.3% versus 82.4%) and closer agreement (kappa=0.89 versus 0.63) with CMR. CONCLUSION: 64-Slice MSCT correlates strongly with CMR in global LV function however in regional LV function 2DE showed better agreement with CMR than 64-slice MSCT.     

Mutations in Drosophila heat shock cognate 4 are enhancers of Polycomb

The homeotic genes controlling segment identity in Drosophila are repressed by the Polycomb group of genes (PcG) and are activated by genes of the trithorax group (trxG). An F(1) screen for dominant enhancers of Polycomb yielded a point mutation in the heat shock cognate gene, hsc4, along with mutations corresponding to several known PcG loci. The new mutation is a more potent enhancer of Polycomb phenotypes than an apparent null allele of hsc4 is, although even the null allele occasionally displays homeotic phenotypes associated with the PcG. Previous biochemical results had suggested that HSC4 might interact with BRAHMA, a trxG member. Further analyses now show that there is no physical or genetic interaction between HSC4 and the Brahma complex. HSC4 might be needed for the proper folding of a component of the Polycomb repression complex, or it may be a functional member of that complex.