Serum integrin-linked kinase (sILK) concentration and survival in non-small cell lung cancer: a pilot study.

BACKGROUND: Integrin-linked kinase (ILK) is an intracellular signaling protein critically involved in cellular growth and motility. In non-small cell lung cancer (NSCLC), increased ILK expression has been associated with decreased recurrence-free and overall survival. Recently, ILK has also been detected in the serum of NSCLC patients. OBJECTIVE: To assess the prognostic impact of preoperative serum ILK (sILK) concentration on overall survival in surgically amenable NSCLC. PATIENTS AND METHODS: Preoperative sILK was quantified by ELISA in 50 newly diagnosed NSCLC patients. After surgery, patients were followed-up for a median interval of 2.5 years. RESULTS: Serum ILK concentrations ranged from 0 to 2.44 ng/ml. Mean sILK was around 2.3 times higher in the 16 patients who died as compared to the 34 patients who survived (1.04 vs. 0.45 ng/ml, p = 0.001). In univariate time-to-event analysis, increased sILK was associated with adverse survival [Hazard ratio (HR): 4.03, 95 % CI: 2.00-8.13, p < 0.001]. This association prevailed after multivariable adjustment for several clinical, demographic, and laboratory parameters (HR: 3.85, 95 % CI: 1.53-9.72, p = 0.004). CONCLUSIONS: Serum ILK shows potential as a novel strong and independent prognostic marker for postoperative survival in surgically amenable NSCLC.

Nosocomial acquisition of Pseudomonas aeruginosa resistant to both ciprofloxacin and imipenem: a risk factor and laboratory analysis.

In vitro, ciprofloxacin can select for dual resistance to fluoroquinolones and imipenem in Pseudomonas aeruginosa via a mutation in the regulatory gene, mexT, which downregulates OprD and upregulates MexEF-OprN. We performed a nested case-control study of patients in two medical intensive care units participating in an observational cohort study. Patients colonized or infected with P. aeruginosa resistant to both ciprofloxacin and imipenem (cases) were compared to controls. The presence of OprD and OprN from cases was evaluated by Western blot. In total, 44 cases were compared to 132 controls. Imipenem exposure [adjusted odds ratio (AOR) = 11.4, p = 0.044] was significantly associated with case status, but fluoroquinolone use was not (AOR = 1.0, p = 0.998). Neither OprD nor OprN were detected in any isolate. Fluoroquinolone use was not a risk factor for acquisitions of dually resistant P. aeruginosa. The absence of OprN in these isolates suggests that dual resistance is not due to mexT mutations.

Influence of hypotensive and normotensive anesthesia on platelet aggregability and hemostatic markers in orthognathic surgery.

This prospective randomized study investigated the influence of normotensive and hypotensive general anesthesia on platelet aggregability, intraoperative blood loss and parameters of plasmatic coagulation during extensive orthognathic surgery. A total of 30 patients were randomly allocated for either normotensive anesthesia maintained by continuous infusion of propofol and remifentanil (NORMO, n=10) or hypotensive anesthesia, whereby hypotension was induced by increasing the infusion rate of remifentanil (HYPO-R, n=10) or by administration of nitroglycerin (HYPO-N, n=10). Whole blood platelet aggregability was significantly reduced during hypotension compared to normotensive anesthesia (P<.01, HYPO-N and HYPO-R vs. NORMO). Mean arterial blood pressure during hypotension correlated well with adenosinediphosphate- (R=.712, P<.001) and collagen-induced platelet aggregability (R=.685, P<.001). Within hypotensive study groups, postoperative fibrinogen levels were significantly different, whereas intraoperative platelet aggregability, postoperative platelet count, prothrombin time, activated partial thromboplastin time and antithrombin levels were not different. Normotensive anesthesia, however, caused significant decreases in platelet count (-29%), prothrombin time (-24%), fibrinogen (-41%) and antithrombin (-28%) and a significant prolongation in activated partial thromboplastin time (+21%) and thrombin time (+18%). There was a trend to reduced intraoperative blood loss in hypotensive study groups; however, differences were not significant. In conclusion, induced hypotension--independent of substances used for induction of hypotension--reduces intraoperative platelet aggregability, subsequently protecting the coagulation system against subclinical consumption coagulopathy. Induced hypotension-caused platelet dysfunction does not lead to an increased intraoperative blood loss, but quite on the contrary shows a trend to reduced intraoperative blood loss, possibly by preventing platelet-induced subclinical consumption coagulopathy.

From delegation to specialization: nurses and clinical trial co-ordination.

This paper considers an area of clinical research that has been delegated by physician-researchers to nurses and others in the United States, that of clinical trials co-ordination. It uses interviews with nurse trial co-ordinators to explore the occupational processes by which the boundaries of work enactment and the definition of work have been established by nurses and others. It then discusses the occupational processes that have been established to formalize a role for nurses in clinical research. It raises the question of (and offers speculation on) whether specialization alone will distinguish nursing from other occupational groups engaged in clinical research work.

Bronchoplastic procedures in malignant and nonmalignant disease: multivariable analysis of 144 cases.

OBJECTIVES: We sought to analyze the experience with bronchoplastic procedures over a 7-year period and to determine putative prognostic factors for survival. METHODS: From 1991 to 1997, 144 bronchoplastic procedures were performed for non-small cell lung cancer (n = 123), small cell lung cancer (n = 5), carcinoid tumor (n = 10), and metastases of extrathoracic malignant tumors (n = 6). There were 111 sleeve lobectomies, 17 bilobectomies, 4 lobectomies with carinal resection, 8 sleeve pneumonectomies, and 4 bronchotomies without parenchymal resection. Multivariable analysis included risk factors, such as age, sex, type of bronchoplastic procedure (bronchotomy, lobectomy, bilobectomy, or pneumonectomy), additional angioplasty, TNM staging, histology, radicality of resection, respiratory risk (forced expiratory volume in 1 second, percent predicted < 60), cardiovascular risk, and adjuvant therapy. RESULTS: Overall 1- and 3-year survival was 72% and 52%, respectively. The overall 30-day mortality was 8.3% (5.4% for single sleeve lobectomies). Multivariable analysis demonstrated 4 risk factors for survival. High tumor stage, type of bronchoplastic procedure, impaired lung function, and presence of cardiovascular risk were associated with a poor outcome. Univariate analysis showed reduced survival in patients with sleeve pneumonectomies (1-year survival, 25%). CONCLUSIONS: Bronchoplastic procedures for central tumors and sleeve pneumonectomies are associated with poor survival. Careful selection of these patients, as well as of patients with impaired lung function and cardiovascular risk factors, is mandatory.

[Complete resection of isolated lung metastasis from breast carcinoma results in a strong increase in survival]. / La resezione completa delle metastasi polmonari isolate in seguito a carcinoma mammario prolunga significativamente la sopravvivenza.

BACKGROUND: Surgical treatment of pulmonary resection for metastatic disease has been proven a valuable therapeutic concept for a variety of neoplasms. Concerning breast cancer, at least 25% of patients develop distant metastases. In spite of increasingly sophisticated palliative therapies, the survival of these patients did not appear significantly prolonged during the last 25 years (19-32 months following diagnosis) and about 95% die from metastatic disease. METHODS: Between 1977 and 1997, three epidemiological comparable groups out of a total of 125 patients of our clinic were treated for isolated pulmonary metastasis following breast cancer. Complete data from 96 patients were retrospectively analyzed following stratification to three groups according their surgical therapy: C, complete resection, 28 patients; I, incomplete resection, 34 patients; N, no resection, 34 patients. RESULTS: Comparison of the three therapy methods concerning stage, histology and receptor levels of the primary tumor, number of metastases and the disease free interval (DFI), as well as adjuvant therapy modalities yielded no significant differences. Mean survival of group C was with 79 months (5-years-survival 80%, 10-years-survival 60%) significantly better compared to groups I and N (p < 0.00002). Mean survival of group I and N was not significantly different (15.5 and 9 months respectively). The DFI had no impact on the survival of group C, but showed a high correlation with the survival of group N (R2 = 0.81). CONCLUSIONS: Routine chest X-ray is necessary in the follow-up of breast cancer patients and if coin lesions occur, thoracic surgeon should be contacted.

Early detection of preeclampsia by determination of platelet aggregability.

Preeclampsia is still a leading cause of maternal and fetal morbidity and mortality. There is evidence for the involvement of platelets. Therefore, we investigated the suitability of corrected whole blood impedance aggregometry as an early predictor of preeclampsia in 71 consecutive, high-risk pregnancies. According to the occurrence of preeclampsia, defined postpartum by an independent investigator, and the stage of pregnancy (early and late, cutoff: 25 weeks of gestation), four study groups were defined. Platelet aggregation data were corrected for the influence of hematocrit and platelet count by a special purpose software package. Women developing preeclampsia showed significantly higher platelet aggregation response compared to controls in early and late pregnancy. In early pregnancy, all women developing preeclampsia had aggregation responses to collagen higher than the highest responses among the controls. Hence, this test had a 100% positive predictive value of subsequent preeclampsia. Despite being significantly increased, platelet aggregability was of minor predictive value in late pregnancy. We conclude that preeclampsia is accompanied by exaggerated platelet aggregability, particularly perceptible early in the course of pregnancy. We propose collagen-induced whole blood platelet aggregation with correction for the influence of hematocrit and platelet count for early detection of preeclampsia.

Changes of platelet surface antigens in patients suffering from abdominal septic shock.

Sepsis and related syndromes account for a high morbidity and mortality caused by the development of multiorgan failure. Pathogenesis of sepsis is complex, involving humoral as well as cellular factors. Since the role of platelets is still undefined in this concern, we investigated CD63, CD62P, CD36, and CD31 expression on platelets of patients in septic shock (n = 18) using a flow cytometric assay in whole blood. Samples were drawn within 24 hours of onset. We found thrombocytopenia accompanied by a significantly higher expression of CD63, CD62P, and CD31 and a significant downregulation of CD36 in comparison to healthy volunteers (n = 18). Changes in CD63 and CD62P expression indicates platelet activation. Because CD62P, CD36, and CD31 mediate interaction of platelets with leukocytes, subendothelial matrix and probably endothelial cells as well as platelet adhesion/aggregation, our findings suggest an involvement of platelets in leukocyte/endothelial cell interaction in septic shock. We suspect that thrombocytopenia is not due to bone marrow depression, but rather is due to consumption of highly activated platelets in the microcirculation. We feel that our observations may offer a rationale for potentially beneficial effects of antiplatelet therapy in sepsis; however, further studies have to evaluate its beneficial impact as well as its potential risk for bleeding complications.

Physician administrators and the reorganization of federally sponsored treatment research for AIDS.

Scholars of modern medicine are concerned with the implications of the movement of physicians into "elite" administrative positions in medical practice settings. To date, empirical studies of physician administrators have focused on their response to disputes that arise between medical and non-medical groups. This paper uses the case of federally funded treatment research for AIDS in the United States to explore the actions of physician administrators and the implications of those actions, in resolving intra-professional conflict. The findings suggest that the actions of elite physician administrators sometimes serve to enhance the fortunes of medical professionals. The findings further suggest that the actions of elite physician administrators sometimes serve to reproduce and affirm professional status distinctions that exist within the broader context of health delivery.

Pleural and bone marrow metastasis from supratentorial oligoastrocytoma grade III.

We report a 62-year-old man with symptomatic metastasis to the pleural cavity and the bone marrow from a supratentorial oligoastrocytoma grade III, 24 years after the initial symptoms. Before tumor dissemination, the patient underwent brain surgery four times in 5 years. Six months after the last treatment, extraneural dissemination to the right pleural cavity was discovered. Despite resection of the pleural metastasis, local and distant spread to the bone marrow developed. The patient died 5 months after the occurrence of extraneural tumor metastasis. It is speculated that repeated brain surgery and extended survival may promote extraneural dissemination of supratentorial oligoastrocytoma grade III.

Preoperative chemotherapy followed by concurrent chemoradiation therapy based on hyperfractionated accelerated radiotherapy and definitive surgery in locally advanced non-small-cell lung cancer: mature results of a phase II trial.

PURPOSE: To evaluate the feasibility and efficacy of an intensive multimodality approach with combination chemotherapy, hyperfractionated accelerated chemoradiotherapy, and definitive surgery in prognostically unfavorable subgroups of locally advanced non-small-cell lung cancer stages IIIA and IIIB (LAD-NSCLC). PATIENTS AND METHODS: Following staging, including mediastinoscopy, 94 patients with inoperable LAD-NSCLC were treated preoperatively with chemotherapy (three courses of split-dose cisplatin and etoposide [PE]) followed by concurrent chemoradiotherapy (one course of PE combined with 45 Gy hyperfractionated accelerated radiotherapy). After repeat mediastinoscopy, patients underwent surgery 4 weeks postradiation. RESULTS: Of 94 consecutive patients (52 stage IIIA [> or = two lymph node levels involved] and 42 stage IIIB [no pleural effusion, no supraclavicular nodes]), 62 (66%) completed induction and underwent surgery. Complete resection (R0) was achieved in 50 (53% of all patients) and pathologic complete response (PCR) in 24 (26%). After a median follow-up of 43 months, the median survival time was 20 months for IIIA, 18 months for IIIB, and 42 months for R0 patients. Calculated survival rates at 4 years were 31%, 26%, and 46%. Two patients died of sepsis preoperatively and four died postoperatively of pleural empyema (n = 1), stump insufficiency (n = 2), and cardiac failure (n = 1). Other toxicities were acceptable-mainly hematologic during chemotherapy or chemoradiotherapy and esophagitis during chemoradiotherapy. CONCLUSION: This intensive multimodality treatment is feasible and demonstrates high efficacy in prognostically unfavorable LAD-NSCLC subgroups with high R0 rates and improved long-term survival compared with historical controls

Variable platelet response to low-dose ASA and the risk of limb deterioration in patients submitted to peripheral arterial angioplasty.

A group of 100 patients with intermittent claudication (70 male, 30 female), treated with I00 mg ASA per day, were followed over 18 months after elective percutaneous balloon angioplasty. Platelet function was monitored over a period of 12 months by corrected whole blood aggregometry (CWBA). Upon stimulation by arachidonic acid (AA), adenosine diphosphate (ADP) and collagen, CWBA-results were obtained by an electronic acquisition and evaluation system correcting for hematocrit and platelet count of the blood sample. All patients showed a completely inhibited platelet response to AA stimulation. Comparison of the CWBA-results with clinical parameters revealed that reocclusions at the site of angioplasty occurred exclusively in male patients for which CWBA failed to prove an inhibition of aggregation upon both agonists, ADP and collagen, and for these patients the risk of complication is at least 87% higher (p = 0.0093). Only 40% of male patients show the expected effect of ASA on in vitro platelet aggregation at any given point in time and CWBA is capable of predicting those male patients which are at an elevated risk of reocclusion following peripheral angioplasty.

Advances in the understanding of lung cancer.

Lung cancers still represent an incurable group of malignancies, where we have to admit that therapy, be it surgery, chemotherapy or radiation, still fails. The emphasis in research has centered on exogenous factors causing the initiation and progression of the different types of lung cancer, especially exposure to tobacco smoke. But so far we have learned that endogenous factors play an equal, if not a more important role, in the onset of this group of diseases. Cancer arising spontaneously never appears to be due to one specific factor, but experimental cancers have been shown to do so. In this light, recent advances in molecular biology have pointed out the relevance of the role of oncogenes and tumor suppressor genes in the pathogenesis of lung cancers. It is the purpose of this paper to review these latest findings, especially from a genetic point of view.

Racial variation in lung cancer.

Lung cancer claimed about 153,000 lives in 1994 in the United States. Despite research overall lung cancer survival has still not improved during the last 20 years, with 5-year relative survival remaining about 13%. In addition several epidemiologic and molecular studies showed a difference in the incidence of lung cancer in the three major races. The aim of our study was to investigate the variations of race in lung cancer patients, in order to identify potential risk factors linked to the different racial status. In this light we compared a 10 years lung cancer data of black population from Howard University Hospital, Washington D.C., U.S.A. and a 20 years data of white population from the Vienna University Hospital, Austria. Our results did not show any significant difference in mean age or tumor localization in both groups, but highlighted a remarkable difference in the incidence of the lung cancer histological types also according to the sex. In this respect it could be more successful to consider carcinogenesis like a protracted process of gene function deregulation in response to cell injury from exposure to genotoxic substances with individual specificity.

Ethnic variations in lung cancer.

Cancer of the lung is the most frequent cancer in the world, but with wide geographical variation in risk. It is most spread among males of all races worldwide, the only exception being its incidence among Chinese women aged 70 years and older. When comparing the different ethnic groups we have to consider that besides inhaling cigarette smoke actively or as a passive smoker the exposure to occupational carcinogens varies considerably according to different work places. In our study we compared 10 years of data from African-Americans in Howard University Hospital, Washington D.C. with 20 years of data from the white population in the University Hospital of Vienna, Austria. Ethnic patterns are generally consistent within each group in terms of both incidence and mortality. The difference in susceptibility between the sexes, the three major racial groups and already proven differences in genetic variations indicate the difference between individuals concerning the initiation and progression of lung cancer.

Survival after surgical treatment of recurrent pulmonary metastases.

OBJECTIVE: Resection of lung metastases is a generally accepted therapeutic strategy today. This retrospective study was performed in order to estimate the value of an aggressive surgical approach in recurrent metastatic disease of the lung. METHODS: The survival rates of 42 patients undergoing repeated resectional treatment for recurrent lung metastases (group A) were compared to the outcome of a total of 288 patients after a single surgical intervention for lung metastases (group B). Survival rates and the relative effects of the various prognostic factors were calculated according to Kaplan-Maier and Mantel Cox or Wilcoxon test. Histology of the primary tumors in group A consisted of 18 carcinomas, 22 sarcomas and two melanomas, in group B the distribution was 64% carcinoma, 27% sarcoma and 9% melanoma. The mean follow-up period was 88.5 months for group A and 27 months for group B. RESULTS: The overall survival rate for group A was 48% at 5 years and 30% at 10 years, the survival rate for group B was 34% at 5 years. CONCLUSION: Long-term survival rates superior to those after single resectional treatment for lung metastases encourage an aggressive surgical approach for this disease.

Influence of UW solution on in vitro platelet aggregability.

Bleeding problems in orthotopic liver transplantation (OLT), starting immediately after reperfusion of the graft, are complicating the outcome of transplantation. Platelets may be involved in this situation, but there is still a lack of information about the influence of UW solution on platelet function. We evaluated the effect of UW solution on in vitro platelet aggregability in healthy volunteers using whole blood electrical aggregometry and concluded, that UW solution causes impaired platelet aggregability and may contribute to bleeding problems during OLT. The mechanism of impairment remains unclear, since central pathways as well as membrane receptors seem to be involved. Furthermore, our data support the necessity of extended flushing of the liver graft after reperfusion.