Temporal patterns of the cerebral inflammatory response in the rat lithium-pilocarpine model of temporal lobe epilepsy

To better understand the role of inflammatory responses in temporal lobe epilepsy, we characterized Interleukin1-beta (IL1-beta), Nuclear Factor-kappaB (NF-kappaB), and Cyclooxygenase-2 (COX-2) expression together with neurodegeneration in the rat lithium-pilocarpine model. The immunohistochemical expression of IL1-beta, NF-kappaB, and COX-2 started by 12 h post-injection, persisted for 24 h (status epilepticus period), and returned to basal levels by 3 and 6 days (latent period). The regional distribution of IL1-beta, NF-kappaB, and COX-2 occurred mainly in structures prone to develop neuronal damage. Using double-staining protocols, we detected IL1-beta expression in glial cells, COX-2 expression in neurons, and NF-kappaB in both cell types. The presence of Fluoro-Jade-B-positive degenerating neurons was associated with IL1-beta, NF-kappaB, and COX-2 proteins expression during status epilepticus but not during the latent period while neurons were still degenerating. These data suggest that seizure-related IL1-beta, NF-kappaB, and COX-2 expression may contribute to the pathophysiology of epilepsy by inducing neuronal death and astrocytic activation.     

Retrorectal cystic hamartomas. Report of one case

Retrorectal cystic hamartomas (RCH) are rare congenital lesions of the presacral space, of which 68 cases are reported under different terms. Clinicopathologic features are usually constant and similar to the present case. A 23-year-old woman complained of abdominal and perineal pains for several months. Physical examination revealed a nodular mass in the posterior part of the rectum. A pelvic MRI showed a 5.5 cm cystic retrorectal mass compressing the rectum. The patient underwent surgical resection. Pathologic examination found an ill-defined nodular mass, composed by numerous cysts surrounded by fibroadipose tissue. Cysts were lined by different epithelia: keratinized and non keratinized squamous, transitional, ciliated and mucus-producing columnar epithelia. Few mucinous glands were noted, connected to some cysts. These epithelial structures were surrounded by connective tissue in which well-differentiated bundles of smooth muscle fibers were present without well-formed muscularis. The RCH differential diagnosis includes principally congenital cysts: epidermal cysts, cystic teratomas, dermoid cysts, anal gland cysts and rectal duplications. An embryologic origin of RCH from remnants of the postanal gut is currently accepted. Loco-regional inflammatory process frequently complicates this lesion and can cause perirectal fistulae. RCH also possesses a malignancy potential, with development of adenocarcinomas. To avoid these complications, complete excision is recommended.     

Computer-aided detection versus independent double reading of masses on mammograms

PURPOSE: To evaluate the use of a computer-aided detection (CAD) system (designed for mammographic mass detection) to help improve mass interpretation and to compare CAD results with independent double-reading results. MATERIALS AND METHODS: Screening mammograms from 500 cases were collected; 125 of these cases were screening-detected cancers, and 125 were interval cancers. Previously obtained screening mammograms (ie, prior mammograms) were available in all cases. All mammograms were analyzed by a CAD system, which detected mass regions and assigned a level of (cancer) suspicion to each mass. Ten experienced screening radiologists read the prior mammograms. For independent interpretation with CAD, the suspicion rating assigned to each finding by the radiologist was weighted with the CAD output at the area of the finding. CAD markers on areas that were not reported by the radiologist were not used. Independent double reading was implemented by using a rule to combine the levels of suspicion assigned to findings by two radiologists. Results were evaluated by using localized-response receiver operating characteristic analysis. RESULTS: In a total of 141 cases, there was a visible abnormality at the location of the cancer on the prior mammogram, and 115 of these were classified as mass cases. For prior mammograms that depicted masses, the mean sensitivity of the radiologists, as averaged among the false-positive rates lower than 10%, was 39.4%; this increased by 7.0% with CAD and by 10.5% with double reading. Differences among single, double, and CAD readings were statistically significant (P <.001). CONCLUSION: Although independent double reading yields the best detection performance, the presence and probability of CAD mass markers can improve mammogram interpretation.     

Pattern of energy expenditure during simulated competition

PURPOSE: To determine how athletes spontaneously use their energetic reserves when the only instruction was to finish in minimal time, and whether experience from repeated performance changes the strategy of recreational athletes. METHODS: Recreational road cyclists/speed skaters (N = 9) completed three laboratory time trials of 1500 m on a windload braked cycle. The pattern of energy use was calculated from total work and from the work attributable to aerobic metabolism, which allowed computation of anaerobic energy use. Regional level speed skaters (N = 8) also performed a single 1500-m time trial with the same protocol and measurements. RESULTS: The serial trials were completed in (mean +/- SD) 133.8 +/- 6.6, 133.9 +/- 5.8, 133.8 +/- 5.5 s (P > 0.05 among trials); and in 125.7 +/- 10.9 s in the skaters (P < 0.05 vs cyclists). The [OV0312]O(2peak) during the terminal 200 m was similar within trials (3.23 +/- 0.44, 3.34 +/- 0.44, 3.30 +/- 0.51 (P > 0.05)) versus 3.91 +/- 0.68 L.min-1 in the skaters (P < 0.05 vs cyclists). In all events, the initial power output and anaerobic energy use was high and decayed to a more or less constant value ( approximately 25% of peak) over the remainder of the event. Contrary to predictions based on an assumed "all out" starting strategy, the subjects reserved some of their ability to perform anaerobic work for a terminal acceleration. The total work accomplished was not different between trials (43.53, 43.78, and 47.48 kJ in the recreational athletes, or between the cyclists and skaters (47.79 kJ). The work attributable to anaerobic sources was not different between the rides (20.67, 20.53, and 21.12 kJ in the recreational athletes). In the skaters, the work attributable to anaerobic sources was significantly larger versus the cyclists (24.67 kJ). CONCLUSION: Energy expenditure during high-intensity cycling seems: 1) to be expended in a manner that allows the athlete to preserve an anaerobic energetic contribution throughout an event, 2) does not appear to have a large learning effect in already well trained cyclists, and 3) anaerobic energy expenditure may be the performance discriminating factor among groups of athletes.     

Peptide-targeted PEG-liposomes in anti-angiogenic therapy

Peptides with the RGD amino acid sequence show affinity for the alpha(v)beta(3) integrin, an integrin which is over-expressed on angiogenic endothelium and involved in cell adhesion. A peptide with the sequence ATWLPPR has been demonstrated to show affinity for the vascular endothelial growth factor (VEGF) receptor, a receptor involved in the proliferation of endothelial cells. By coupling these peptides to liposomes, these liposomes can serve as a site-specific drug delivery system to tumor endothelial cells in order to inhibit angiogenesis. In the present study we demonstrate that the coupling of cyclic RGD-peptides or ATWLPPR-peptides to the surface of PEG-liposomes results in binding of these liposomes to endothelial cells in vitro. Subsequent studies with RGD-peptide targeted liposomes in vivo also demonstrate specific binding to the tumor endothelium.     

Screening for lung cancer in the Netherlands: the role of spiral CT scan

The very poor prognosis of lung cancer has barely changed in the last two decades despite all efforts. However, prognosis is better when the disease is detected earlier, so that curative surgery or radiotherapy can be applied. Lung cancer screening in the past by chest X-ray did not lead to a decrease in lung cancer mortality, because the chest X-ray has low sensitivity for early invasive stages. With the advent of the low-dose spiral CT scan it has become feasible to detect early invasive stage I lung cancer in 80-90%. Modern screening for lung cancer by spiral CT scan could possibly decrease lung cancer mortality. Despite the first favourable results of screening the question remains whether lung cancer screening will be cost-effective. These questions can only be resolved in a randomised controlled trial with lung cancer mortality as unbiased end-point. Such a study should be initiated in the Netherlands, a country with large experience in screening trials and a good health care system. Only after lung cancer screening has proven to be cost-effective can appropriate implementation be recommended to prevent uncontrolled and opportunistic diffusion of this new screening technique into clinical practice in the near future.     

Screening for breast cancer on basis of individual risk assessment for women ineligible for the national population screening program

For healthy women, without malignancies in their personal histories, a positive family history for breast cancer is the single indication for individual breast surveillance outside the population screening. Management of women is based on individual risk assessment. A cumulative risk of 20% and more, as a result of a positive family history, will in practice be an indication for breast surveillance. This threshold is not evidence-based yet, nor are data available on the benefits of this surveillance efficacy. When a personal cumulative risk of more than 30% exists to develop breast cancer, a consultation with a clinical geneticist involved in a family cancer clinic should be offered. Surveillance of women with a high-risk cumulative risk should preferably be included in a prospective study design. Only in this way will data about compliance and the estimates of different ways of surveillance become available. There is no convincing evidence that population screening for women aged 40-49 years does lead to important mortality reduction in combination with a good balance between pros and cons for the women involved. Women in the age category 50-75 years, with breast cancer in their personal histories, who are not followed anymore, should be informed by their specialist about participating (again) in the population breast screening. There is no evidence of mortality reduction as a result of breast self-examination nor of palpation performed by a physician. However, awareness of the own body can be useful for early recognition of breast abnormalities; it may reduce the delay between the first recognizable symptom and the subsequently initiated therapy.     

Uptake of pentamidine in Trypanosoma brucei brucei is mediated by three distinct transporters: implications for cross-resistance with arsenicals

The trypanocidal action of pentamidine is dependent on the rapid, selective accumulation of this drug by the parasite. We have investigated pentamidine transport by the bloodstream and procyclic life cycle stages of Trypanosoma brucei brucei. In bloodstream forms, 50 to 70% of [(3)H]pentamidine was transported by an adenosine-sensitive pentamidine transporter (ASPT1) that displayed a K(m) value of 0.26 +/- 0.03 microM and K(i) values of 0.45 +/- 0.04 and 2.5 +/- 0.8 microM for adenine and berenil, respectively. These values are very similar to those for inhibition of [(3)H]adenosine uptake by the P2 adenosine/adenine transporter, suggesting that ASPT1 and P2 may be identical. The remaining 30 to 50% of [(3)H]pentamidine transport was mediated by a low-capacity high-affinity pentamidine transporter (HAPT1) and a high-capacity low-affinity pentamidine transporter (LAPT1), with K(m) values of 36 +/- 6 nM and 56 +/- 8 microM, respectively. HAPT1 was inhibited by propamidine but displayed only low affinity to berenil and stilbamidine, whereas LAPT1 was not inhibited by any of these diamidines. Neither transporter was inhibited by melarsen oxide. In procyclics, an HAPT1-analog (procyclic pentamidine transporter; PPT1) was characterized, but no adenosine-sensitive pentamidine transport could be detected. Treatment with ionophores revealed that PPT1 may be a proton/pentamidine cotransporter.