Analysis of global gene expression changes in human bronchial epithelial cells exposed to spores of the allergenic fungus, Alternaria alternata.

Exposure and sensitivity to ubiquitous airborne fungi such as Alternaria alternata have long been implicated in the development, onset, and exacerbation of chronic allergic airway disorders. This present study is the first to investigate global changes in host gene expression during the interaction of cultured human bronchial epithelial cells and live Alternaria spores. In in vitro experiments human bronchial epithelial cells (BEAS-2B) were exposed to spores or media alone for 24 h. RNA was collected from three biological replicates per treatment and was used to assess changes in gene expression patterns using Affymetrix Human Genome U133 Plus 2.0 Arrays. In cells treated with Alternaria spores compared to controls, 613 probe sets representing 460 individual genes were found differentially expressed (p ≤ 0.05). In this set of 460 statistically significant, differentially expressed genes, 397 genes were found to be up-regulated and 63 were down-regulated. Of these 397 up-regulated genes, 156 genes were found to be up-regulated ≥2 fold. Interestingly, none of the 63 down-regulated genes were found differentially expressed at ≤-2 fold. Differentially expressed genes were identified following statistical analysis and subsequently used for pathway and network evaluation. Interestingly, many cytokine and chemokine immune response genes were up-regulated with a particular emphasis on interferon-inducible genes. Genes involved in cell death, retinoic acid signaling, and TLR3 response pathways were also significantly up-regulated. Many of the differentially up-regulated genes have been shown in other systems to be associated with innate immunity, inflammation and/or allergic airway diseases. This study now provides substantial information for further investigating specific genes and innate immune system pathways activated by Alternaria in the context of allergic airway diseases.

Prospective multicenter study on urologic complications after radical surgery with or without radiotherapy in the treatment of stage IB-IIA cervical cancer.

A national collaborative group has conducted a multicenter prospective study on the use of a specific glossary for the complications associated with the treatment of cervical cancer, which were analytically described in 1989. This report analyzes the urologic complications with particular reference to radical surgery in stage IB-IIA cancer cases. In the prospective multicenter clinical study 2024 patients with frankly invasive cervical cancer were enrolled (IB = 1041; IIA = 308; IIB = 384; IIIA-B = 237; IV = 54). This report considers 1349 patients with stage IB-IIA disease. Treatment modalities in this group of patients were: type III radical surgery in 21.9%; type III radical surgery followed by radiotherapy in 20.8%; type III radical surgery preceded by radiotherapy in 7.3%; type II radical surgery in 3.1%; type II radical surgery followed by radiotherapy in 8.4%; type II radical surgery preceded by radiotherapy in 18.8%; surgery plus chemotherapy plus radiotherapy in 3.5%; radiotherapy alone in 16%. In this case series 873 complications were registered, and among these 341 (39.1%) were described in the urinary tract. Among 277 bladder complications 47.3% were grade 1; 47.3% grade 2, and 5.4% grade 3. Among 64 ureter complications 59.4% were grade 1; 17.2% grade 2, and 23.4% grade 3. Distribution of severe urinary complications was different according to site (bladder or ureter) and treatment modalities (radical surgery alone: bladder 1.3%, ureter 1.3%; radical surgery followed by radiotherapy: 1.4% bladder, 2.8% ureter; radical surgery preceded by radiotherapy: 3% bladder, 0% ureter). Different distributions of severe urinary complication were also observed in respect to stage (IB vs IIA); treatment: elective vs nonelective. In 673 patients treated with radical surgery plus or minus radiotherapy 123 relapses were registered (18.2%). Incidence of relapse was not different in patients suffering from mild/severe complications vs patients without complications. Disease-free survival, death from tumor, and death from other causes were not different in the group with complications in comparison to the group without complications.

Weekly Cisplatin induction chemotherapy in high-risk cervical-cancer patients with bulky tumor - a phase-ii study.

In this study we evaluated efficacy and toxicity of a neoadjuvant chemotherapy regimen before radiation therapy or surgery in high-risk cevical cancer patients. Between January 1988 and July 1993, 37 out of 40 consecutive patients with bulky cervical carcinoma (>40 mm) received chemotherapy consisting of six (range 4-9) weekly courses of cisplatin (1 mg/kg), followed by radical surgery and/or radiotherapy. Thirty-six patients completed the planned sequence of treatment. Overall response rate was 65% after induction chemotherapy (complete 0% and partial 65%) and 73% (complete 57% and partial 16%) after definitive treatment. After a median follow-up of 23 (range 4-61) months the median duration of response was 29, 19 and 11 months for complete partial and non-responders respectively. Toxicities from induction chemotherapy were mild to moderate, reversible and tolerable and did not affect the subsequent application of the definitive treatment. The proposed cisplatin neoadjuvant chemotherapy regimen gave positive results in a good number of cases with low toxicity and without interfering with the definitive radio-surgical treatment of this group of high-risk patients. The number of cisplatin courses for best effect remains to be established.

Transvaginal sonography in the diagnosis of pelvic malignant recurrence: integration of sonography and needle-guided biopsy.

The aim of this study was to evaluate the efficiency of transvaginal sonography and sonography plus needle biopsy in detecting pelvic malignant recurrence. We scanned 24 patients already treated for gynecological malignancy, 21 of whom underwent needle biopsy under sonographic guidance. Thirteen patients were affected by cervical cancer, ten by ovarian cancer, and one by endometrial-ovarian carcinoma. Sonography detected 16 solid or cystic-solid masses (median size 52 mm, range 15-85 mm), one case of ascites, and one liquid mass (hematoma). All the patients in whom a suspicious mass was detected had recurrence. In the six patients in whom no mass was visible, two had recurrence. Needle biopsy was able to demonstrate recurrence in 17 patients (also in two false-negative scans). In one, even though sonography detected a mass, the histological sample was negative, but recurrence was later diagnosed by laparotomy.Accuracy, sensitivity and specificity of transvaginal sonography were respectively 91.6%, 89.4% and 100%. The positive predictive value was 100% and the negative predictive value was 71.4%. Transvaginal sonography was shown to be a useful means of detecting pelvic recurrence.

Analysis of complications of cervix carcinoma treated by radiotherapy using the Franco-Italian glossary.

We analysed the complications of 215 patients with uterine cervix cancer, treated by radiotherapy (RT) alone. It was done according to the rules of the Franco-Italian glossary, presented at the 7th ESTRO meeting, held in The Hague on September 1988. They were ranked by organ sites and by degrees of gravity. The analysis was done on the total number of complications and they were scored at the highest reached grade of gravity. Seventy one complications were found in 55 patients; they were studied by patient, degree of severity, time of onset, organ system and grade, time of onset and grade, time of onset and organ sites, stage and RT doses and brachytherapy volumes. The importance of the study of complications is stressed, particularly when treatment combines external RT and brachytherapy; some guidelines are given to avoid severe complications.

Localization and management of occult breast lesions.

Mammography is an effective method for finding lesions of the breast which are occult at clinical examination. For occult lesions biopsy, including as little surrounding tissue as possible, it is necessary that they be located before surgery in order to improve the pathological process and the cosmetic outcome for the patients. Among the clinically occult lesions shown only by mammography, the frequency of breast cancers ranges from 10% to 47%. There are several different techniques for locating hidden lesions of the breast. We have employed the insertion of a single rigid needle into the breast, with X-ray confirmation of correct positioning. Forty-nine patients underwent this technique in our Institution and in all cases we were able to achieve a correct insertion of the needle at the X-ray check (the tip of the needle was less than 1 cm from the lesion). The target lesion was removed (as confirmed by X-ray of the surgical specimen) in all cases at the first attempt. In our study we found 11 invasive and 7 in situ tumours (36%). No complications delaying the surgical biopsy or the recovery of the patients were observed.

Pelvic mass biopsy by operative transvaginal sonography (OTVS).

Operative transvaginal sonography (OTVS) is widely used in clinical Obstetrics and Gynecology, however it has no definite role in Gynecologic Oncology. Between January 1990 and February 1991, we performed 18 ultrasonically-guided biopsies on suspected pelvic malignancies. The aim of our work was to assess to efficiency of OTVS in imaging, evaluating and biopsying pelvic masses. Fifteen patients had already been treated for gynecological malignancy, 3 were at their first evaluation. We used a Bruel & Kjaer mechanical transducer (7.5 MHz, type 8538). Biopsy needles were Menghini type (Surecut) 23 cm long, 16 or 18 G. The paper describes the results of the 18 biopsies. One false negative histological evaluation and one inadequate sample were obtained. No complications were observed. From our preliminary data, ultrasound-guided transvaginal scans may be usefully used in imaging and biopsying pelvic masses. It is a safe technique, easy to perform and well accepted by the patients.

[Occult mammary lesions: preoperative localization. Review of the literature]. / Lesioni mammarie occulte: localizzazione preoperatoria. Analisi della letteratura.

The preoperative localisation of occult mammary lesions can be performed using fine needle biopsies, thus limiting esthetic damage in those patients in whom histological tests prove the lesion to be benign. Various methods have been proposed over the past 20 years. The purpose of this paper is to evaluate published data in order to determine which is the most appropriate method in terms of simplicity and efficacy.

Posterior Cervical Paraspinal Musculature Morphology: A Cadaveric and CT Scan Study.

Positive identification of posterior cervical paraspinal muscles were made on computed tomography (CT) scans and correlated with the findings on cadaveric cross-sections of corresponding levels. Two frozen, fixed cervical cadaveric sections were CT scanned at various levels, then sliced cross-sectionally at the appropriate thickness. Individual muscles of the posterior cervical area were then identified on the cadaveric section and the corresponding CT scan section. In both specimens, identification of the individual muscles was possible on CT scan. Detection of normal anatomical variations of the cervical muscles was also possible on CT scans, but muscle fiber orientation was not. It is concluded that positive identification of posterior cervical paraspinal musculature on CT scan is possible. This provides the physical therapist with a greater understanding of both cervical cross-section anatomy and gross anatomy of the posterior cervical paraspinal musculature. Information obtained through CT scanning can assist the physical therapist in treatment of patients with injuries to the soft tissue structures of the cervical spine. J Orthop Sports Phys Ther 1986;8(1):15-26.