Role of brachytherapy in malignant melanoma: a preliminary report

From August 1979 to May 1986, various brachytherapy techniques were applied at Memorial Sloan Kettering Cancer Center (MSKCC) in an adjuvant setting with/without surgery and external radiation therapy in the management of advanced malignant melanoma. Thirty-three patients underwent brachytherapy procedures. The patients' ages ranged from 35 to 82 years, with a median age of 56 years. Fourteen patients had disease localized to the implant site, whereas 19 patients also had disseminated disease elsewhere. The indications for implant were residual gross disease (21), microscopically positive margins (3), and histologically negative but clinically close margins of resection (9). Local control at the implant site was noted in 80% of patients at 6 months and 42% of patients at 1 year; two patients had reached 54 months and 72 months with no evidence of disease. Local control was 100% (9/9) in patients with histologically negative but clinically close margins of resection, and 48% (11/23) with microscopically positive margins and/or gross residual disease. Complications were seen as follows: delay in wound healing (1), wound infections (4), radiation enteritis (1), small bowel obstruction (1). The present study suggests that brachytherapy combined with surgery can achieve a good local control in patients with negative but clinically close margins of resection. In patients with gross residual disease who are at a high risk for local recurrence, approximately one-half can be locally controlled with this approach. These preliminary results should be tested in a prospective controlled study.     

Cardiac magnetic resonance imaging assessment of regional and global left atrial function before and after catheter ablation for atrial fibrillation

Background  

Ablation of the left atrium and pulmonary veins antrum (PVAI) can be an effective treatment of atrial fibrillation (AF). However, there is discrepancy in the literature regarding the effect extensive ablation has on left atrial (LA) function. We sought to evaluate the effect that AF ablation procedures has on global and regional wall motion as assessed by cardiovascular magnetic resonance imaging (MRI).     

The isoprenoid end product N6-isopentenyladenosine reduces inflammatory response through the inhibition of the NFκB and STAT3 pathways in cystic fibrosis cells

Objective

N6-isopentenyladenosine (iPA) is an intermediate of the mevalonate pathway that exhibits various anti-cancer effects. However, studies on its anti-inflammatory activity are scarce and underlying molecular mechanisms are unknown. Therefore, we aimed to investigate the ability of iPA to exert anti-inflammatory effects in the human cystic fibrosis (CF) cell model of exacerbated inflammation.

Materials and methods

TNFα-stimulated CF cells CuFi-1 and its normal counterpart NuLi-1 were pre-treated with increasing concentrations of iPA and cell viability and proliferation were assessed by MTT and BrdU assays. The effect of iPA on IL-8 and RANTES secretion was determined by ELISA, and the activation and expression of signaling molecules and selenoproteins were studied by Western blot. To assess the direct effect of iPA on NFκB activity, luciferase assay was performed on TNFα-stimulated HEK293/T cells transfected with a NFκB reporter plasmid.

Results

We demonstrated for the first time that iPA prevents IL-8 and RANTES release in TNFα-stimulated CF cells and this effect is mediated by increasing the expression of the direct NFκB inhibitor IκBα and decreasing the levels of STAT3. Consistent with this, we showed that iPA inhibited TNFα-mediated NFκB activation in HEK/293T cells. Finally, we also found that iPA improved the levels of glutathione peroxidase 1 and thioredoxin reductase 1 only in CF cells suggesting its ability to maintain sufficient expression of these anti-oxidant selenoproteins.

Conclusions

Our findings indicate that iPA can exert anti-inflammatory activity especially in the cases of excessive inflammatory response as in CF.

     

Individual effects of estradiol and progesterone on food intake and body weight in ovariectomized binge rats

The individual roles of estradiol (E) and progesterone (P) in the control of food intake and body weight in ovariectomized (OVX) rats were investigated. Six groups of OVX Sprague-Dawley rats (n = 9/group) were assigned to one of three 4-day cyclic hormone treatments: two groups were treated with E benzoate; two groups were treated with P; two groups were treated with both (EP). All rats had continuous access to chow and water throughout this 4-week study. One group of rats within each hormone treatment condition was fed chow ad libitum, and the second was subjected to a binge schedule: chow ad libitum plus 1-h access to an optional fat source on Monday, Wednesday, and Friday. A seventh OVX group (n = 8) received the oil vehicle and chow. This group was included to monitor body weight and to verify hormone efficacy. The main findings were: (1) relative to rats receiving only P, E alone or EP attenuated 24-h chow intake tonically and cyclically, i.e. intake on Day 4, which models estrus, was lower in E and EP than in P, and also was lower than intake on Day 2, which models diestrus. In contrast, (2) neither E nor EP detectably affected optional fat intake during the 1-h fat access period relative to rats receiving only P when data were collapsed across the entire study. However, (3) E and EP had large effects on fat intake relative to P during the 1-h fat access period at the start of the study, but not at the end, when bingeing was fully established. (4) E and EP led to lower and apparently normal levels of body weight compared to rats receiving only the oil vehicle or only P. These results indicate that (1) administration of E alone has similar effects as co-administration of E and P on feeding and body weight in rats bingeing on fat, (2) with or without P, the inhibitory effects of E on meal size are compromised when bingeing on fat, and (3) the effects of E on binge size change dynamically as bingeing develops.     

Reliability and Validity of a Novel Muscle Contusion Device

Context:

Many models have been employed to replicate skeletal muscle injury associated with trauma; however, most are restricted to 1 level of severity.

Objective:

To create and validate an injury-producing device that could generate multiple levels of injury severity.

Design:

Validation study.

Patients or Other Participants:

Twenty-six male Wistar rats, 3 to 4 months old.

Intervention(s):

A contusion device was developed and its ability to deliver consistent impacts was validated alone and in the presence of an experimental animal. A free-falling mass (267 g) was adjusted to the desired height (40, 50, 60, or 70 cm) and then dropped.

Main Outcome Measure(s):

Peak load, peak displacement, impulse, energy, and velocity peak were measured. Injury severity was determined using magnetic resonance imaging.

Results:

Outcome measures observed from the device alone were different by height (F_18,136  =  21.807, P < .001, 1−β  =  1.0). Outcomes using the experimental animals were also dependent on height (F_14,102  =  68.679, P < .001, 1−β  =  1.0). Linear regression analyses indicated that height accounted for 17% to 89% of the variance.

Conclusions:

Mild to moderate and moderate to severe injuries can be replicated with this device, which will be useful in evaluating clinical treatments on acute muscle injury.     

Plasma acylated ghrelin levels are higher in patients with chronic atrophic gastritis

OBJECTIVES: Ghrelin is mainly produced by the endocrine cells of the gastric oxyntic mucosa. For this reason we decided to investigate the modification of the circulating levels not only of total but also of acylated ghrelin in a series of patients with chronic atrophic gastritis. DESIGN: Twenty-five patients with chronic atrophic gastritis and 25 healthy subjects were studied. In all 50 subjects gastrin and total and acylated ghrelin levels were evaluated. All patients underwent endoscopy with multiple biopsies, and the possibility of Helicobacter pylori infection was investigated. RESULTS: Significantly higher acylated ghrelin levels (82.8 +/- 61.3 vs. 35.1 +/- 17.1 pmol/l), acylated/total ghrelin ratio (0.422 +/- 0.202 vs. 0.152 +/- 0.085) and gastrin levels (1071 +/- 816 vs. 66 +/- 22 ng/l) were observed in the 25 patients with chronic atrophy than in the healthy subjects. Otherwise, no significant relationships were found when total ghrelin was correlated with the presence of atrophy, or with gastrin levels. In the healthy subjects, but not in the patients, acylated and total ghrelin levels were significantly higher in female than in male patients. CONCLUSIONS: The increase in acylated ghrelin levels and in the acylated/total ghrelin ratio in patients with atrophy of the body and fundus can be explained by hypothesizing an increase in the acylating process in the presence of gastric atrophy. It suggests that there may be a compensatory increase in plasma active ghrelin concentration in response to gastric atrophy, a condition which causes a loss of ghrelin-producing cells and an increase in gastric pH.     

Role of axillary ultrasound examination in the selection of breast cancer patients for sentinel node biopsy

BACKGROUND: Sentinel node biopsy (SNB) is a time-consuming procedure that can be avoided in presence of axillary metastases. The aim of this study was to assess the accuracy of ultrasound scan (US) in the prediction of axillary nodes status in patients scheduled for SNB. METHODS: Axillary US was performed and when feasible, a core biopsy of suspicious nodes was taken. The nodal status as assessed by US and/or core biopsy was compared with final histology. RESULTS: Of the 132 patients enrolled, 31 (23.5%) had suspicious axillary nodes according to US; 19 (61.3%) were true positive, whereas 12 cases (38.7%) were not. In 14 of 31 suspicious cases an US-guided core-biopsy was taken, which in 11 of 14 cases (78.5%) confirmed the neoplastic involvement. Overall, core biopsy of the nodes correctly predicted the final histology in 13 of 14 cases (92.8%). CONCLUSIONS: The US of axillary nodes, possibly associated with core biopsy, improved the preoperative evaluation of breast cancer patients scheduled for SNB.