Biochemical studies of the matrix of craniovertebral chordoma and a metastasis.

Glycosaminoglycans of human chordoma and a metastasis were studied. The glycosaminoglycans were derived from the extracellular matrix and consisted of chondroitin 4- and 6-sulphate, keratan sulphate and hyaluronate. The ratio of chondroitin sulphate to keratan sulphate was much lower in the metastasis than in the primary. Proteoglycan extracted with 4M guanidinium chloride and purified by associative density-gradient centrifugation was assessed on Sepharose 2B before and after reduction and alkylation. The result of this experiment suggested that only a small proportion of the proteoglycans were aggregated.     

Giant condyloma (Buschke—Loewenstein tumor) of the anorectum

Summary A case of giant condyloma of Buschke and Loewenstein is presented. The clinical course and pathology of these tumors are reviewed. This case illustrates the delay in establishing the diagnosis in spite of numerous biopsies. It is emphasized that the only effective treatment is wide local excision.     

Inversion-recovery single-shot cardiac MRI for the assessmentof myocardial infarction at 1.5 T with a dedicated cardiac coil

Objective The aim of this study was to assess the diagnostic accuracy of imaging myocardial infarction with a two-dimensional (2D) single-shot inversion-recovery (IR)-gradient-echo (GE) sequence compared with a standard 2D segmented IR-GE sequence at 1.5 T using a dedicated cardiac coil. Methods 22 patients with myocardial infarction documented in the past 3-12 months were examined at 1.5 T using a 5 channel cardiac coil. Imaging of delayed enhancement was performed 15 min after administration of 0.2 mmol of gadopentetate dimeglumine per kilogram of body weight. Immediately after completion of the single-shot sequence, which allows for coverage of the entire ventricle during a single breath-hold with nine slices, the segmented IR sequence was started. Infarct volumes, infarct transmurality and contrast-to-noise ratios (CNRs) of infarcted and healthy myocardium were compared between both techniques. Results Despite a moderate, non-significant loss of CNR (CNR(single-shot IR)=31.2±4.1; CNR(segmented IR)=37.9±4.1; p=0.405), the 2D single-shot technique correctly determined infarct size when compared with the standard 2D segmented IR-GE sequence. Assessment of both infarct volume (r=0.95; p<0.0001) and transmurality (r=0.97; p<0.0001) is possible, with excellent correlation of both techniques. Conclusion Single-shot delayed enhancement imaging during a single breath-hold is feasible at 1.5 T with the use of a dedicated cardiac coil. Despite a moderately lower CNR, the single-shot technique allows for fast and accurate determination of infarct size with high spatial resolution and has the potential to reduce electrocardiogram and breathing artefacts.     

Venous thrombectomy in patients presenting with iliofemoral vein thrombosis after renal transplantation

In this study 14 patients presented with 15 episodes of iliofemoral vein thrombosis after renal transplantation. Seven patients (group 1) had viable renal grafts and were treated with conventional anticoagulation. Eight patients (group 2) had non-viable renal grafts and were subjected to graft nephrectomy and simultaneous venous thrombectomy without anticoagulation. The patients in group 2 had rapid resolution of the signs and symptoms of the iliofemoral vein thrombosis, and noninvasive vascular investigation at follow-up revealed competent and patent deep veins in all patients. In contrast, only 50% of the patients in group 1 had normal venous studies at follow-up. We recommend that renal transplant recipients who develop iliofemoral vein thrombosis and nonviable allograft postoperatively should be subjected to venous thrombectomy at the time of graft nephrectomy.     

In silico prediction of substrate properties for ABC-multidrug transporters

Overexpression of ABC (ATP-binding cassette)-type drug efflux pumps, such as ABCB1, ABCC1 and ABCG2 in cancer cells confers multi-drug resistance (MDR) and represents a major cause of treatment failures in cancer therapy. Furthermore, there is increasing evidence for the important contribution of ABC-transporters to bioavailability, distribution, elimination and blood-brain barrier permeation of drug candidates. This review presents an overview on the different computational methods and models pursued to predict ABC-transporter substrate properties of drug-like compounds. They range from linear discriminant analysis to pharmacophore modelling and machine learning algorithms. Many of these models show a satisfying performance within the study-specific, defined chemical space but general applicability for the whole drug-like chemical space still needs to be proven. First attempts aiming towards selectivity profiling for ligands of the two polyspecific transporters ABCB1 and ABCG2 is also discussed. This might pave the way for a pharmacological profiling of compound series with special focus on their ADMET (absorption, distribution, metabolism, excretion and toxicity) properties.     

Identification and frequency of CCR5Δ32/Δ32 HIV-resistant cord blood units from Houston area hospitals

Objectives

The use of umbilical cord blood (CB) that is genetically resistant to HIV infection has been proposed as a novel stem cell therapy for the treatment of patients with AIDS. These genetically unique CB units (CBUs) should be present in public CB banks at a predicted frequency.

Methods

The chemokine (C‐C motif) receptor 5 (CCR5) genotypes of CBUs donated to the M. D. Anderson CB Bank by four Houston area hospitals were determined by polymerase chain reaction (PCR) and DNA sequencing.

Results

The frequency of CCR5Δ32/Δ32 CBUs was consistent with the frequency of the CCR5Δ32 allele in human populations, and was apparently dependent on the ethnic population of the parents of the newborns from whom the CBUs were collected.

Conclusions

Routine genotyping to identify HIV‐resistant CBUs could create a bank of CB‐derived stem/progenitor cells with which to treat HIV infection.     

Analgesia and serum concentrations of extradural,subdural and intraperitoneal fentanyl in a rat model

The effects of epidural, subdural and intraperitoneal fentanyl were determined on the tail flick response of the rat using the response latency as a measure of analgesia. Dose-time-response curves were generated for incremental doses of fentanyl administered at constant injection volumes. Serum concentrations at varying doses were determined using a radioimmunoassay technique. It was found that serum concentrations for extradural, subdural and intraperitoneal fentanyl were similar at the low doses, but differed significantly at higher doses suggesting that pharmacokinetic differences may be concentration dependent. Extradural administration of naloxone (0.004 mg) was able to antagonize extradural fentanyl (8.0 micrograms), a dose eight-fold greater than the lowest maximally effective dose. The relationship between serum fentanyl concentrations and administered doses suggest that the analgesic properties of extradural and subdural fentanyl are in part dependent on centrally mediated actions.