Integrin signaling potentiates transforming growth factor-beta 1 (TGF-ß1) dependent down-regulation of E-Cadherin expression - Important implications for epithelial to mesenchymal transition (EMT) in renal cell carcinoma.

Signal transduction through the transforming growth factor-beta 1 (TGF-ß1) pathway affects epithelial to mesenchymal transition (EMT), partly by modulation of E-Cadherin expression. The concurrent impact of extracellular matrix driven regulation of integrin signaling on EMT has not been well characterized. We assessed the cumulative effect and molecular mechanisms of TGF-ß1 and integrin signal transduction on E-Cadherin in a renal cell cancer (RCC) model. Stimulation of RCC cells with TGF-ß1 demonstrated a three-fold increased expression of integrin αv. A ligand of integrin αv-ß3, (cyclopentapeptide containing Arginyl-Glycyl-Aspartic acid motif, RGD), was used to mimic integrin signaling. Treatment of cells with RGD and TGF-ß1 demonstrated significantly greater E-cadherin depletion than either ligand alone. This cooperative action on E-Cadherin expression is regulated by transcription factor Snai1 and is followed on a cellular level by increased cellular mobility as evidenced in a wound healing assay. Subsequent silencing of potential downstream mediators of the cumulative action of RGD and TGF-ß1 was carried out by small interfering RNA transfection and confirmed by Western blotting and/or RT-PCR. SiRNA mediated silencing of FAK and PINCH1 independently abrogated the cumulative effect of RGD and TGF-ß1 on E-Cadherin expression. We have identified a novel mechanism through which extracellular matrix event transduction by integrins further augments TGF-ß1 related effects on EMT. Molecular machinery involved in the integrin αv-TGF-ß1 interplay may represent a therapeutic target in RCC.

Psychosocial effects of level of information and severity of disease on head-and-neck cancer patients.

This study examined the psychosocial effects of levels of information available to patients and compared them with those of disease severity. A questionnaire with multiple-choice and open-ended questions assessing quality of life in various domains (e.g., fears and worries, functioning in the family) and scales assessing anxiety, anger, and depression were administered to patients and their partners or closest relatives. The subjects were 55 head-and-neck cancer patients (40 men and 15 women) in disease stages I to IV, grades of tumors G1 to G3-4, with disease durations ranging from three months to 21 years. They were divided into three groups on the basis of the amounts of information they had about their disease and prognosis, and again on the basis of disease severity, based on stages and patients' evaluations. The numbers of psychosocial variables differentiating significantly between the groups deviated significantly from chance in both groupings. The results showed more effects for information than for disease severity. The highly informed were better adjusted in interpersonal relations and had more intimacy with family, but had more fears, anxiety, changes in their lives, worries about health, and concern with physical symptoms. The reports of partners were fewer and lent some support to those of patients. Disease severity affected mostly fears, anxiety, and worries about health.

[Pharyngo-gastric anastomosis following pharyngo-laryngo-esophagectomy for cancer].

Cancer of the hypopharynx and cervical esophagus usually presents in an advanced stage. Treatment is therefore aggressive and involves a combination of surgery and radiotherapy. Pharyngo-laryngo-esophagectomy, gastric pull-up and pharyngo-gastric anastomosis has become the method of choice for extensive tumors in the past decade. 3 men, aged 51, 51 and 74, respectively, who had extensive cancer of the hypopharynx and cervical esophagus and underwent this procedure are described. 2 made full, rapid recoveries without complications, but in the third, there were postoperative complications due to severe chronic lung disease. Proper selection of patients may reduce considerably the morbidity and mortality of this surgical procedure.

[Diagnosis of Arnold-Chiari malformation by electronystagmography].

3 patients with Arnold-Chiari malformation with vertigo as the sole clinical presentation are described. 2 of them had been undiagnosed for many years despite repeated examinations, including CT scans. The third patient was diagnosed 2 weeks following the initial vertiginous attack. Downbeating nystagmus demonstrated by electronystagmography, indicating a pathological lesion at the craniocervical junction, was the key finding that led to the diagnoses. Following this finding, CT scan directed to the craniocervical junction showed the typical image of Arnold-Chiari malformation. The cases presented emphasize the important contribution of electronystagmography in the evaluation of vertigo due to intracranial lesions. However, computerized imaging examination remains the main diagnostic tool for intracranial pathologic processes.

Life satisfaction and health in cancer patients, orthopedic patients and healthy individuals.

Life satisfaction (LS) is one of a set of constructs defining quality of life. Previous studies showed that LS was sometimes related to health and sometimes not. The study was designed to examine the relation of LS as a general construct to satisfaction in specific domains. We assumed that there is a tendency to maintain an acceptable level of LS even under stressful and threatening conditions, that it is related to optimism and that the likelihood of attaining satisfaction in a particular domain affected the selection of domains on which LS is based. We expected that in cancer patients LS would be related to more domains but not to health. The study was done with 55 head-and-neck cancer patients, of all stages and grades of tumor; 51 orthopedic patients, victims of accidents with good recovery chances; and 55 healthy individuals. The healthy individuals and orthopedic patients were matched (in terms of group values) to the cancer patients in age, gender and education. Single-item measures of LS and optimism, and a questionnaire with 49 multiple-choice items assessing adjustment in 13 domains were administered to all subjects. The results showed that in cancer patients LS was related to most domains but not to health and not to optimism, whereas in the other groups it was related to few domains including health, and also to optimism. The findings support the tendency to maintain LS with the materials available to the individual, and show that health is related to LS only if its maintenance or attainment are realistic goals. Thus, both bottom-up and top-down theories of LS are supported.

Psychosocial problems in head-and-neck cancer patients and their change with time since diagnosis.

BACKGROUND: Little is known about the psychosocial effects of cancer survivors especially after the first stage of adjustment. The study was designed to provide information about the major psychological problems of head-and-neck cancer patients and their change with time since diagnosis. PATIENTS AND METHODS: The subjects were 55 head-and-neck cancer patients, 40 men and 15 women with disease stages I to IV, grade of tumors G1 to G3-4, and disease duration in the range of 3 months to 21 years. A questionnaire with multiple-choice and open-ended questions assessing adjustment in 14 domains (e.g., fears and worries concerning health, functioning in the family) was administered to patients and their partners or closest relatives as well as scales assessing anxiety, anger and depression. RESULTS: The results showed that the domains that were most problem-laden included coping with health problems, fears, communication with the partner and social relations. Comparing the problems of patients in different time periods (0.5-1.5 years after diagnosis, 1.5-5 years, and over 5 years) showed that many medical problems decreased with time but most psychological ones including anxiety and anger deteriorated markedly. CONCLUSIONS: Head-and-neck cancer patients suffer from a broad range of psychosocial problems that become exacerbated with time. The deterioration in quality of life may reflect 'patient burnout' which could be decreased by acquiring adequate coping skills.

Granulation tissue concentrations of ofloxacin after oral administration in invasive external otitis.

Following the fourth dose of 400 mg orally administered ofloxacin, simultaneous external ear canal granulation tissue and serum ofloxacin concentrations were estimated in 15 patients with invasive external otitis. The granulation tissue concentration was 2.2 (range 1.17-4.34) times higher than the serum concentration and 3.73 (range 1.95-11.00) times higher than the MIC90 of ofloxacin against Pseudomonas aeruginosa.

What do cancer patients' spouses know about the patients?

A large body of research shows that social support in general and of family members in particular plays an important role in determining cancer patients' quality of life. We assumed that the spouse's information about how the patient experiences the situation determines the spouse's ability to help. The present study was designed to examine how much the spouse knows about the attitudes and experiences of their husband or wife who is a cancer patient, and whether this knowledge depends on the questions' structure, disease duration, its severity, or level of patient's information about the disease and prognosis. A questionnaire with multiple-choice and open-ended questions assessing 13 domains (e.g., fears and worries concerning health, functioning in the family, and anxiety) was administered to patients and their partners. Subjects were 55 head-and-neck cancer patients, 40 men and 15 women, with disease stages I to IV, grade of tumors G1 to G3-4, and disease duration of 0.5 to 21 years. The results showed that correspondence between the patients' and their spouses' responses was very low, and was not affected by the structure of the questions or the disease's duration and severity. Correspondence was high only in patients informed about their disease. In the discussion, it was pointed out that when the patient is informed, communication channels in the family are opened and this brings about an increase in the spouses's information about the patient and hence in the spouse's ability to provide the patient the needed social support as a psychotherapeutic agent and a friend. The cancer nurse may play a crucial role in instituting the patient-spouse dialogue.

Oral ofloxacin therapy for invasive external otitis.

The clinical efficacy and safety of orally administered ofloxacin (400 mg twice daily) were evaluated in 24 adult patients (17 men and 7 women; mean age, 65.8 years) with pseudomonal invasive external otitis (IEO). The patients were divided into two groups: group A, (n = 9) suffering from a mild form of IEO, and group B (n = 15), suffering from a more severe form of the disease. Diabetes mellitus was the main underlying disease in these patients. Pseudomonas aeruginosa was the only pathogen in 18 infected ears and part of the polymicrobial flora in an additional 6. Cure was observed in 83.3% of the patients. Two of the cured patients required more than one course of ofloxacin treatment. Development of P aeruginosa resistant to ofloxacin (n = 3) and severe allergic reaction (n = 1) required the discontinuation of ofloxacin therapy. Other side effects such as nausea, arthralgia, and vaginal itching were minimal. Oral administration of ofloxacin seems to be an effective, convenient, relatively safe, and economical therapy of IEO caused by the susceptible organism.

Cervical necrotizing fasciitis of odontogenic origin.

Necrotizing fasciitis is a severe soft tissue infection caused by both aerobic and anaerobic bacteria and is characterized by a rapid extension along fascial planes and by necrosis of soft tissues. The disease rarely occurs in the head and neck. Three cases of necrotizing fasciitis of the neck after a dental infection are presented. The difficulty in diagnosing the early stage of this condition in relation to other soft tissue infections of odontogenic origin in the neck is discussed. The importance of an early diagnosis followed by an appropriate combination of medical, surgical, and dental treatment is emphasized.

Changes in auditory function associated with 2-cyano-butyl-acrylate adhesive implanted in the middle ear of experimental animals.

The effects on auditory function caused by the implantation of 2-cyano-butyl-acrylate adhesive in the middle ear was investigated in experimental animals. Auditory brainstem responses to click stimuli were used to measure hearing thresholds prior to and following implantation of 2-cyano-butyl-acrylate adhesive in the middle ear of guinea pigs. A permanent and deep threshold shift observed at 2 months in 62% of the examined animals, suggested that this tissue adhesive is an ototoxic middle ear implant material and should not be considered in reconstructive middle ear surgery. The functional data correlate well with some of the previous morphological observations.

Auditory brain-stem responses in guinea pigs following middle ear implantation of Ceravital.

The effects on auditory function caused by implantation of the bioactive glass ceramic Ceravital in the middle ear of guinea pigs was investigated. Auditory brain-stem responses (ABR) were used to measure hearing function. A threshold shift due to a conductive hearing loss was observed immediately post-operatively. This threshold shift increased towards the 20th post-operative day and improved thereafter. Surgical manipulation of the middle ear and biochemical reactions between the Ceravital granules and the middle ear wall may have contributed respectively to the immediate and late temporary ABR threshold shift recorded. However, cochlear function was not affected by middle ear implantation of Ceravital. These results correlate well with morphological studies of Ceravital implanted in the middle ear and give further support to the safe use of Ceravital as an implantation material in middle ear reconstructive surgery.

Functional changes in the brainstem auditory pathways following open-heart surgery.

Measurements of the auditory brainstem responses (ABR) were used to assess the functional integrity of the brainstem auditory pathways following open-heart surgery. Recording of ABR was performed in 31 patients before and after open-heart surgery. The values of ABR measurements were compared to those of a control group of normal-hearing subjects. Postoperative aberrations in ABR were observed in 12 patients. Brainstem transmission time measured as wave I to wave V interpeak latency (I-V IPL) was prolonged in 6 patients and shortened in 8 patients. Concomitant impairment in hearing function was not present, and therefore, these changes most probably reflected a functional alteration in the neurological status of the brainstem. Possible explanations of the postoperative changes in I-V IPL are discussed, however, further studies are needed to clarify the pathogenesis of these changes. Measurement of ABR may prove to be an important adjunct in the overall assessment of the neurological status following open-heart surgery.

Acute airway obstruction and achalasia of the esophagus.

Patients with achalasia tolerate considerable distension of the esophagus. Respiratory symptoms usually are due to regurgitation and pulmonary aspiration of retained food rather than to a space-occupying mechanism. We describe a case of previously undiagnosed achalasia presenting in an elderly woman with symptoms consistent with tracheal obstruction of acute onset.

Dairy products containers as a source of unusual esophageal foreign bodies.

Seven patients were treated during a period of three years in the Otolaryngology department of Tel-Aviv Medical Centre, Israel, for the ingestion of a strange, previously unknown foreign body. The objects had been inadvertently swallowed while eating certain dairy products such as yogurt or sour cream. This rigid, sharp pointed plastic object is a waste product which is punched out from the production line of the foods and their containers. The plastic object is radiolucent and, therefore, difficult to identify on standard roentgenograms. Fluoroscopic examination with a contrast medium was needed for its demonstration. Five patients underwent rigid esophagoscopy under general anesthesia for removal of the foreign body. In two other cases the object was extracted from the piriform sinus under topical anesthesia. This unusual foreign body, although uncommon, poses a potential medical hazard. A high index of suspicion is necessary to make the diagnosis when a patient presents with a history of foreign body ingestion while eating dairy products of soft consistency.