J. Bernheim

Experimental ultrasonic angioplasty: Disruption of atherosclerotic plaques and thrombi in vitro and arterial recanalization in vivo

To investigate the use of high energy ultrasound as an alternative energy for angioplasty, an experimental ultrasonic angioplasty device was developed. The device was studied in two bioassay systems: an in vitro system for the disruption of atherosclerotic plaques and thrombi and an in vivo system for the recanalization of occluded canine femoral arteries. In vitro, sonication efficiently reduced the size of the plaques. Atheromatous plaques (n = 11) disrupted at a rate of 21 +/- 8 s/cm2; complicated plaques (n = 14) disrupted at a rate of 132 +/- 45 s/cm2 (p less than 0.001). Histologic examination revealed that the disruption of the plaques took place without concurrent damage to the media or adventitia. Ninety percent of the disrupted plaque debris had a diameter of less than 20 microns and was composed primarily of cholesterol monohydrate crystals. Solid thrombus (n = 5) weight was reduced from 1.6 +/- 0.2 to 0.4 +/- 0.1 g (p less than 0.0001) after 20 s of sonication. In vivo, sonication resulted in recanalization in all seven arteries tested in seven dogs. The obstruction was reduced from 93 +/- 11% to 18 +/- 7% (p less than 0.001). On histologic examination, the arterial wall injury index was found to be 1.56 +/- 0.42 in the test arteries compared with 1.37 +/- 0.47 in the control arteries (p = NS). The disruption of atherosclerotic plaques and thrombi, together with the efficient recanalization of the occluded arteries, demonstrates the potential of ultrasound angioplasty as a catheter-based technique for angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

Spectral Analysis of Fluctuations in Heart Rate: An Objective Evaluation of Autonomic Nervous Control in Chronic Renal Failure

A quantitative, noninvasive method of assessing autonomic control, based on the spectral analysis of beat-to-beat fluctuations in heart rate (HR), was applied to patients with chronic renal failure (RF). Since the power spectrum of HR fluctuations measures the dynamic nervous control of HR, it can be used to quantitate a normal control system as opposed to a disturbed or depressed system. Indeed, in RF patients, a strong reduction in the HR power spectrum was observed in all frequency ranges, both sympathetically and parasympathetically mediated. A similar depression in autonomic control was demonstrated in patients on hemodialysis or peritoneal dialysis. RF patients not yet undergoing dialysis show a lesser degree of depression. Spectral analysis of HR fluctuations in RF patients makes it possible to quantitate autonomic dysfunction and to reliably measure its development as a function of time, and requires only a 10-min standard electrocardiogram recording.

Aberrant crypt foci in human colons: distribution and histomorphologic characteristics.

Aberrant crypt foci (ACF) are one of the earliest putative preneoplastic, and in some cases, neoplastic lesions in human colons. These microscopic lesions, identified on methylene blue-stained mucosa with a low-power-magnification microscope, are thought to be closely related to the earliest steps in multistage colonic tumorigenesis. We investigated the distribution pattern and histomorphological features of ACF in 74 patients with sporadic colorectal cancer. The distribution pattern shows a slightly higher prevalence with older age. The prevalence of the ACF in sigmoid colon was significantly higher in patients with colorectal cancer as compared with patients with benign colonic diseases. Also, significantly more ACF were detected in distal parts of the large bowel (descending, sigmoid colon, and rectum) than in proximal parts. Of 42 microdissected lesions, 12 were dysplastic and 30 were hyperplastic foci. The average size of dysplastic lesions was significantly larger than hyperplastic foci. More apoptotic bodies were found in dysplastic lesions. These lesions also showed an upward expansion of proliferative compartment and higher proliferation indices expressed as proliferating cell nuclear antigen-labeling index. Lymphoid follicles were frequently observed in the base of both hyperplastic and dysplastic foci (40% and 66.6%, respectively). The coincidence of lymphoid follicles was 2.5 to 8 times higher than expected. These features may be related to further progression of selected ACF during colorectal tumorigenesis.

The Rising Incidence of Adult Acute Epiglottitis and Epiglottic Abscess

OBJECTIVE To examine preliminary observations that the incidence of adult acute epiglottitis has risen between 1986 and 2000. MATERIALS AND METHODS Demographics, annual and seasonal occurrences, clinical presentation, diagnostic procedures, treatment, airway management, and complications of 116 consecutive adult patients with laryngoscopically confirmed acute epiglottitis are presented. RESULTS The mean annual incidence of acute epiglottitis per 100,000 adults significantly increased from 0.88 (from 1986-1990) to 2.1 (from 1991-1995) and to 3.1 (from 1996-2000) (P <.001). This rise seems to be unrelated to Haemophilus influenzae type b infection but related to miscellaneous pathogenic bacteria. During these periods, the number of epiglottic abscesses increased concomitantly with the rise in the incidence of acute epiglottitis (from 4/14 episodes [29%], to 8/38 [21%], and to 16/66 [24%], respectively), showing a relatively constant ratio between both phenomena (P =.843). Twenty-five patients (21%) underwent airway intervention, 16 because of objective respiratory distress and 9 because of imminent respiratory obstruction. Stepwise logistic regression showed that drooling, diabetes mellitus, rapid onset of symptoms, and abscess formation were associated with airway obstruction. Diverse origins for the epiglottic abscess, either from coalescent epiglottic infection or from mucopyocele of the tongue base, are suggested. CONCLUSIONS A rise in the incidence of acute epiglottitis and a concomitant rise in the number of epiglottic abscesses were established. Although the course of acute epiglottitis is often benign and can be safely treated with a conservative management approach, delayed airway obstruction may develop from a few hours to days after admission.

Polypoid Mucosa With Eosinophilia and Glandular Hyperplasia in Chronic Sinusitis: A Histopathological and Immunohistochemical Study

Objective To evaluate the histopathological and immunohistochemical characteristics of chronic sinusitis, with reference to the extent of sinus involvement.

Calcitriol blunts pro-atherosclerotic parameters through NFκB and p38 in vitro

Background  Disturbances in vitamin D3 metabolism are associated with an increased cardiovascular morbidity and mortality. The aim of this study was to assess the effects of calcitriol, the active metabolite of vitamin D3, on pro‐atherosclerotic parameters in human umbilical vein cord endothelial cells (HUVEC).

Platinum-resistance in ovarian cancer cells is mediated by IL-6 secretion via the increased expression of its target cIAP-2

Ovarian carcinoma patients are initially responsive to platinum-based therapy, but eventually become refractory to treatment due to the development of platinum chemoresistance. Elevated levels of interleukin-6 (IL-6) in the sera and ascites of these patients predict poor clinical outcome. Our goal was to analyze the interaction between cisplatin and cisplatin-resistant ovarian cancer cells, and to identify means of circumventing platinum resistance. We studied ovarian carcinoma cell lines and cells drawn from ovarian carcinoma patients. Gene array analyses were performed on ovarian carcinoma cells upon treatment with cisplatin, and the results were validated by ELISA and Western blotting (WB). Cytotoxicity assays were performed on anti-IL-6 Ab-, IL-6-, and cellular inhibitor of apoptosis 2 (cIAP-2) siRNA-treated cells, following cisplatin addition. Our results revealed a highly significant increase in IL-6 and cIAP-2 mRNA and protein levels upon treatment with cisplatin. WB analysis of cisplatin-treated cells exhibited decreased cIAP-2 expression level following anti-IL-6 Ab addition. Furthermore, IL-6 by itself, significantly increased cIAP-2 levels in ovarian carcinoma cells. Finally, cytotoxicity assays showed sensitization to cisplatin following the addition of IL-6 and cIAP-2 inhibitors. In conclusion, cisplatin treatment of ovarian carcinoma cells upregulates IL-6 and cIAP-2 levels while their inhibition significantly sensitizes them to cisplatin. Here, we present cIAP-2 as a novel inducer of platinum resistance in ovarian carcinoma cells, and suggest an axis beginning with an encounter between cisplatin and these cells, mediated sequentially by IL-6 and cIAP-2, resulting in cisplatin resistance. Consequently, we propose that combining IL-6/cIAP-2 inhibitors with cisplatin will provide new hope for ovarian carcinoma patients by improving the current treatment.

Proliferating cell nuclear antigen as a marker of cell kinetics in aberrant crypt foci, hyperplastic polyps, adenomas, and adenocarcinomas of the human colon*

BACKGROUND One of the first steps in multistage colonic carcinogenesis is increased cell proliferation and an upward shift of the proliferation zone of colonic crypts. In the present study, progression in cell kinetics was followed up at all sequential stages of colonic carcinogenesis, starting with aberrant crypt foci (ACF), the earliest putative preneoplastic lesions, hyperplastic and dysplastic polyps, and invasive carcinomas. MATERIALS AND METHODS Colonic tissue and tumor specimens were prospectively obtained from 65 patients treated at our hospital for adenocarcinoma or malignant polyps. For identification of ACFs, dissected mucosal strips obtained from patients with colorectal cancer were stained with 0.1% methylene blue and scanned under dissecting microscope. Paraffin-embedded ACFs and macroscopic lesions were serially sectioned, deparaffinized, and stained with a monoclonal antiproliferating cell nuclear antigen (PCNA) antibody. The PCNA-labelling index (PCNA-LI), expressed as a ratio of positively stained nuclei to total nuclei counted, was calculated separately for basal, middle, and upper colonic crypt compartments. A comparison of the PCNA-LI was made for each compartment in normal mucosa, and hyperplastic and dysplastic lesions. RESULTS A stepwise increase in the PCNA-LI was observed during neoplastic progression of colonic lesions. The two most important variables of increased cell proliferation, expressed as PCNA-LI per crypt compartment, were the presence of dysplasia and the size of dysplastic lesions. CONCLUSIONS In colorectal carcinogenesis, hyperproliferation with upward expansion of proliferative compartment is a characteristic feature at all stages of malignant progression.

Angiogenesis, p53, and c-erbB-2 immunoreactivity and clinicopathological features in male breast cancer

p53, c‐erbB‐2, and tumor microvascular density have been shown to be potential prognostic tools in female breast cancer. Our objective was to assess the significance of these biomarkers as prognostic factors in infiltrating male breast cancer.

Parathyroid hormone stimulates the endothelial expression of vascular endothelial growth factor

Background  We showed previously that parathyroid hormone (PTH) may stimulate the endothelial expression of pro‐atherosclerotic and pro‐inflammatory markers. Considering the impact of PTH on vasculature, we decided to evaluate its effect on mRNA and intra‐cellular protein expressions of endothelial vascular endothelial growth factor (VEGF) taking into account that VEGF may play a role in the pathogenesis of endothelial dysfunctions.