Ultrasound guided percutaneous drainage of splenic abscesses

We present our experience of ultrasound-guided percutaneous drainage with a catheter in 5 splenic abscesses. All the cases were resolved and there was only one relevant complication. The advantages of this treatment compared with surgery and isolated medical treatment are discussed and this technique is proposed as the treatment of choice.     

Dipeptide Derivatives of Primaquine as Transmission-Blocking Antimalarials: Effect of Aliphatic Side-Chain Acylation on the Gametocytocidal Activity and on the Formation of Carboxyprimaquine in Rat Liver Homogenates

Purpose. Dipeptide derivatives of primaquine (PQ) with reduced oxidative deamination to the inactive metabolite carboxypnmaquine were synthesized and evaluated as a novel class of transmission-blocking antimalarials. Methods. Antimalarial activity was studied using a model consisting of mefloquine-resistant Plasmodium berghei ANKA 25R/10, Balb C mice, and Anopheles stephensi mosquitoes. Metabolic studies were performed with rat liver homogenates, and the incubates were analyzed by HPLC. Results. All dipeptide derivatives and glycyl-PQ completely inhibited the appearance of oocysts in the midguts of the mosquitoes at 15 mg/ kg, while N-acetylprimaquine was not active at this dose. However, none of the title compounds were able to block oocyst production at 3.75 mg/kg, in contrast with primaquine. Exception for sarc-gly-PQ, all remaining compounds prevented sporozoite formation in the salivary glands of mosquitoes at a dose of 3.75 mg/kg. Simultaneous hydrolysis to primaquine and gly-PQ ocurred with the following order of V_max/ K_m: for primaquine formation, L-ala-gly-PQ > L-phe-gly-PQ > gly-gly-PQ; and for gly-PQ formation, L-phe-gly-PQ > L-ala-gly-PQ > gly-gly-PQ. In contrast, primaquine was not released from D-phe-gly-PQ, sarc-gly-PQ, and N-acetylprimaquine. Neither carboxyprimaquine nor 8-amino- 6-methoxy- quinoline were detected in any of the incubation mixtures. Conclusions. The title compounds prevent the development of the sporogonic cycle of Plasmodium berghei. Gametocytocidal activity is independent of the rate and pathway of primaquine formation. Acylation of the aliphatic side-chain effectively prevents the formation of Carboxyprimaquine, but the presence of a terminal amino group appears to be essential for the gametocytocidal activity.     

Determination of the Glass Transition Temperatures of Some New Methyl Methacrylate Copolymers Using Modulated Temperature Differential Scanning Calorimetry (MTDSC)

Purpose. The purpose of this study was to determine the glass transition temperatures of new graft copolymers using Modulated Temperature Differential Scanning Calorimetry (MTDSC), and to assess the differences between starch and cellulosic derivatives of methyl methacrylate and between two different drying methods used in their preparation. Methods. Graft copolymers of methyl methacrylate were synthesized and dried by oven or freeze-drying. Surface area measurements and different thermal analysis techniques (Differential Scanning Calorimetry (DSC), Thermogravimetric analysis (TGA) and MTDSC) were used to characterize these copolymers. Results. DSC was not sensitive enough to identify the T_gs of the copolymers, however they were clearly identifiable by MTDSC. T_g values obtained may depend on the method of preparation that also altered their physical characteristics e.g. specific surface area. Cellulose derivatives showed lower T_gs than starch derivatives. The results also depended on the drying method used, thus, freeze dried products had slightly lower T_gs than oven dried products. Conclusions. MTDSC represents a useful thermal technique that allows the identification of glass transitions in these new copolymers with higher sensitivity and resolution than conventional DSC, separating the transition from overlapping phenomena such as decomposition or dehydration. The T_g of this new class of copolymers appeared to be dependent on polymer composition and drying method used.     

Lovastatin-induced Apoptosis of Human Medulloblastoma Cell Lines in vitro

Medulloblastoma is a malignant paediatric central nervous system tumor with a poor prognosis, stimulating the evaluation of improved treatment strategies. Lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, is currently used to treat patients with hypercholesterolemia. This compound also inhibits the production of non-steroidal mevalonate derivatives that are implicated in the control of cellular proliferation, and can induce cell-cycle arrest in vitro. We recently showed that lovastatin inhibited growth and promoted apoptosis of neuroblastoma, the peripheral nervous system cousin of medulloblastoma. Therefore the potential of lovastatin as a possible anticancer drug against medulloblastoma was evaluated in vitro. Four medulloblastoma cell lines, Daoy, UW228, D341 Med and D283 Med, were treated with 1–40µM of lovastatin in vitro. Analysis of cell morphologic changes, cell viability, DNA fragmentation and flow cytometry in all four cell lines showed growth inhibition and induction of apoptosis with lovastatin treatment. As little as 10µM of lovastatin was sufficient to cause a marked reduction in cell numbers, and more than 20µM of lovastatin induced >90% cells to undergo apoptosis, after intervals ranging between 36 and 96h, depending on the cell line. Lovastatin induced apoptosis in these cell lines was concomitant with cell cycle arrest in G1. The attached cell lines UW228 and Daoy were more sensitive to lovastatin than D283 Med and D341 Med. Daoy cells which survived several cycles of lovastatin treatment could still be induced to undergo apoptosis after longer treatment times. The efficient induction of apoptosis by lovastatin favours this drug as a potential new avenue of therapeutic intervention for medulloablastoma.     

Histologic grade and CD44 are independent predictors of axillary lymph node invasion in early (T1) breast cancer.

Background: The detection rate of small, often subclinical breast cancers is increasing in affluent societies. Concomitantly, the demand for more conservative surgical approaches is also increasing among the women affected. Predictors of the absence of nodal invasion would spare many patients with early breast cancer the risks, costs and side effects of lymphadenectomy, and thus treatment with curative intent would be applied using really minimal surgery. Patients and Methods: We reviewed the records of 135 patients with unifocal invasive breast cancers, 2 cm or less in diameter, operated upon at 'Fundación Tejerina-Centro de Patología de la Mama', Madrid, Spain, between January 1993 and December 1997. Full clinical and pathological data were available for all of them, together with estrogen and progesterone receptor determinations, which had been routinely performed in 134 and 133 cases, respectively. Additionally, Ki67, c-erb-B2, p53, nm23, HSP27, HSP60 and CD44std expression was studied on archival, paraffin-embedded tumor material from these same patients by means of immunohistochemistry. Results: In the univariate analysis, only histologic grade 3 (p < 0.001), Ki67 expression in more than 10% of tumor cells (p = 0.005) and CD44std negativity (p = 0.004) were significantly associated with axillary node involvement. In multivariate analysis, histologic grade 3 and CD44std negativity retained statistical significance, and thus emerged as independent predictors of nodal invasion. The combination of both, furthermore, identified a subgroup in which the axillary nodes were invariably affected. Conclusion: Some pathological and molecular features of small breast cancers were able to predict nodal metastasis significantly. However, none, either alone nor combined, was able to exclude axillary node invasion completely. Copyright Copyright 1999 S. Karger AG, Basel     

Skin penetration and kinetics of pristine fullerenes (C60) topically exposed in industrial organic solvents

Pristine fullerenes (C₆₀) in different solvents will be used in many industrial and pharmaceutical manufacturing and derivatizing processes. This report explores the impact of solvents on skin penetration of C₆₀ from different types of industrial solvents (toluene, cyclohexane, chloroform and mineral oil). Yorkshire weanling pigs (n = 3) were topically dosed with 500 μL of 200 μg/mL C₆₀ in a given solvent for 24 h and re-dosed daily for 4 days to simulate the worst scenario in occupational exposures. The dose sites were tape-stripped and skin biopsies were taken after 26 tape-strips for quantitative analysis. When dosed in toluene, cyclohexane or chloroform, pristine fullerenes penetrated deeply into the stratum corneum, the primary barrier of skin. More C₆₀ was detected in the stratum corneum when dosed in chloroform compared to toluene or cyclohexane. Fullerenes were not detected in the skin when dosed in mineral oil. This is the first direct evidence of solvent effects on the skin penetration of pristine fullerenes. The penetration of C₆₀ into the stratum corneum was verified using isolated stratum corneum in vitro; the solvent effects on the stratum corneum absorption of C₆₀ were consistent with those observed in vivo. In vitro flow-through diffusion cell experiments were conducted in pig skin and fullerenes were not detected in the receptor solutions by 24 h. The limit of detection was 0.001 μg/mL of fullerenes in 2 mL of the receptor solutions.