Integration of gene expression profiling and clinical variables to predict prostate carcinoma recurrence after radical prostatectomy

BACKGROUND: Gene expression profiling of prostate carcinoma offers an alternative means to distinguish aggressive tumor biology and may improve the accuracy of outcome prediction for patients with prostate carcinoma treated by radical prostatectomy. METHODS: Gene expression differences between 37 recurrent and 42 nonrecurrent primary prostate tumor specimens were analyzed by oligonucleotide microarrays. Two logistic regression modeling approaches were used to predict prostate carcinoma recurrence after radical prostatectomy. One approach was based exclusively on gene expression differences between the two classes. The second approach integrated prognostic gene variables with a validated postoperative predictive model based on standard variables (nomogram). The predictive accuracy of these modeling approaches was evaluated by leave-one-out cross-validation (LOOCV) and compared with the nomogram. RESULTS: The modeling approach using gene variables alone accurately classified 59 (75%) tissue samples in LOOCV, a classification rate substantially higher than expected by chance. However, this predictive accuracy was inferior to the nomogram (concordance index, 0.75 vs. 0.84, P = 0.01). Models combining clinical and gene variables accurately classified 70 (89%) tissue samples and the predictive accuracy using this approach (concordance index, 0.89) was superior to the nomogram (P = 0.009) and models based on gene variables alone (P < 0.001). Importantly, the combined approach provided a marked improvement for patients whose nomogram-predicted likelihood of disease recurrence was in the indeterminate range (7-year disease progression-free probability, 30-70%; concordance index, 0.83 vs. 0.59, P = 0.01). CONCLUSIONS: Integration of gene expression signatures and clinical variables produced predictive models for prostate carcinoma recurrence that perform significantly better than those based on either clinical variables or gene expression information alone.     

Tobacco smoking, GSTP1 polymorphism, and bladder carcinoma

BACKGROUND: Although cigarette smoking is considered a major risk factor for bladder carcinoma, little is known about the interaction between metabolic genes such as glutathione-S-transferase P1 and tobacco smoking in this process. GSTP1 may play a role in detoxification of tobacco-related carcinogens. METHODS: In this case-control study of 145 cases with bladder carcinoma (male:female = 7.5:1) and 170 noncancer controls (male:female = 3.7:1), the relation between genetic polymorphisms of GSTP1 and susceptibility to bladder carcinoma was investigated and the gene-environment interaction between tobacco smoking and GSTP1 polymorphism was evaluated. Epidemiological data were collected for all cases and controls by a standard questionnaire. Polymorphisms of GSTP1 were measured by polymerase chain reaction-restriction fragment length polymorphism. The logistic regression model in SAS was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Cigarette smoking was confirmed as a risk factor of bladder carcinoma with an OR of 3.1 (95% CI: 1.7-5.9) after controlling for potential confounding factors. The OR for pack-years of smoking as a continuous variable was 2.4 (95% CI: 2.0-2.8). The ORs were 7.6 (95% CI: 1.18-49.51) for isoleucine/valine (Ile/Val) and 6.5 (95% CI: 1.01-41.56) for Ile/Ile when the homozygous Val/Val was considered as comparison group after adjusting for age, gender, race, and education. The adjusted OR for interaction between smoking and the GSTP1 (any Ile genotype) was 11.42 (95% CI: 0.53-248.15). CONCLUSIONS: The results indicate that the Ile 105 allele is associated with an increased risk of bladder carcinoma and suggest that individuals who smoke and possess the Ile allele might be at increased risk for bladder carcinoma.     

Arterielle Pulskonturanalyse zur Messung des Herzindex unter Veränderungen der Vorlast und der aortalen Impedanz

ZusammenfassungHintergrund Die arterielle Pulskonturanalyse wurde zur Bestimmung des Herzindex (CI) sowohl bei herzchirurgischen als auch bei kritisch kranken Patienten während unterschiedlichen klinischen Bedingungen validiert. Der anhand der Pulskonturanalyse bestimmte Herzindex (CI_PC) zeigt eine gute Übereinstimmung mit dem durch arterielle (CI_TD) oder durch pulmonalarterielle Thermodilution (CI_PA) bestimmten Herzindex. Die Genauigkeit der Pulskonturanalyse unter Bedingungen des offenen Thorax mit Veränderungen der Vorlast und der aortalen Impedanz ist jedoch unklar. Daher wurden CI_PC, CI_TD und CI_PA in Abhängigkeit dieser Veränderungen durch Sternotomie verglichen.Methodik 28 Patienten während elektiver koronarer Bypassoperation wurden untersucht. CI_PC und CI_TD, sowie CI_PA bei 6 Patienten, wurden vor sowie nach Sternotomie bestimmt, und die relativen Veränderungen CI_PC und CI_TD und CI_PA berechnet.Ergebnisse Die Sternotomie resultierte bei 25 von 28 Patienten in einem signifikanten Anstieg des CI. Eine Regressionanalyse wurde zwischen CI_PC und CI_TD vor bzw. nach Sternotomie (r² = 0,87, p<0,0001, r² = 0,88, p<0,0001) sowie zwischen CI_PC und CI_PA, vor bzw. nach Sternotomie (r² = 0,85, p<0,0001, r² = 0,93, p<0,01) und zwischen CI_PC and CI_TD (r² = 0,72, p<0,0001) durchgeführt. Eine Bland Altman-Analyse ergab für Bias (m) und Grenzen der Übereinstimmung (2SD) zwischen CI_PC und CI_TD vor und nach Sternotomie sowie zwischen CI_PC und CI_TD: m = –0,03 l/min/m², 2SD = –0,34 bis 0,28 l/min/m², m = –0,06 l/min/m², 2SD = –0,45 bis 0,33 l/min/m² und m = –0,02 l/min/m², 2SD = –0,47 bis 0,44T l/min/m². Schlussfolgerung Veränderungen der Vorlast und der aortalen Impedanz während Sternotomie beeinflussen nicht die Genauigkeit der arteriellen Pulskonturanalyse. CI_PC, CI_TD, und CI_PA zeigen unter diesen Bedingungen eine gute Übereinstimmung.     

Managing panic disorder in general practice

BACKGROUND: Panic disorder (PD) is common in the community and contributes to significant distress and decreased quality of life for people who suffer from it. Most people with PD will present in the first instance to their general practitioner or hospital emergency department for assistance, often with a focus on somatic symptoms and concerns. OBJECTIVE: This article aims to assist the GP to manage this group of patients by providing an outline of aetiology, approaches to assessment, and common management strategies. DISCUSSION Although GPs have an important role to play in ruling out any causal organic basis for panic symptoms, the diagnosis of PD can usually be made as a positive diagnosis on the basis of careful history taking. Thorough and empathic education is a vital step in management. The prognosis for PD can be improved by lifestyle changes, specific psychological techniques, and the judicious use of pharmacotherapy.     

Encounters with indigenous patients in Australian general practice

The BEACH program, a continuous national study of general practice activity in Australia, gives an overview of consultations with indigenous patients. Between 1998 and 2003, general practitioners recorded 5476 consultations with people who identified themselves as being of Aboriginal and/or Torres Strait Islander origin. These accounted for approximately 1% of total BEACH encounters for the 5 year period. In this article we compare 'indigenous encounters' with total BEACH encounters. This provides a backdrop against which articles in this issue of Australian Family Physician can be further considered.     

Modern concepts of treatment and prevention of lightning injuries

Lightning is the second most common cause of weather-related death in the United States. Lightning is a natural atmospheric discharge that occurs between regions of net positive and net negative electric charges. There are several types of lightning, including streak lightning, sheet lightning, ribbon lightning, bead lightning, and ball lightning. Lightning causes injury through five basic mechanisms: direct strike, flash discharge (splash), contact, ground current (step voltage), and blunt trauma. While persons struck by lightning show evidence of multisystem derangement, the most dramatic effects involve the cardiovascular and central nervous systems. Cardiopulmonary arrest is the most common cause of death in lightning victims. Immediate resuscitation of people struck by lightning greatly affects the prognosis. Electrocardiographic changes observed following lightning accidents are probably from primary electric injury or burns of the myocardium without coronary artery occlusion. Lightning induces vasomotor spasm from direct sympathetic stimulation resulting in severe loss of pulses in the extremities. This vasoconstriction may be associated with transient paralysis. Damage to the central nervous system accounts for the second most debilitating group of injuries. Central nervous system injuries from lightning include amnesia and confusion, immediate loss of consciousness, weakness, intracranial injuries, and even brief aphasia. Other organ systems injured by lightning include the eye, ear, gastrointestinal system, skin, and musculoskeletal system. The best treatment of lightning injuries is prevention. The Lightning Safety Guidelines devised by the Lightning Safety Group should be instituted in the United States and other nations to prevent these devastating injuries.     

Quality improvement in laparoscopic radical prostatectomy for pT2 prostate cancer: impact of video documentation review on positive surgical margin

PURPOSE: We correlated intraoperative video documentation and pathology findings to understand the mechanisms by which positive surgical margins occur and improve the surgical technique. MATERIALS AND METHODS: Between January 2003 and May 2004, 240 consecutive patients underwent laparoscopic radical prostatectomy, of whom 180 had pT2 prostate cancer and represent the population of this study. After the first 90 patients (group 1) we started a quality assurance study, analyzing intraoperative video recordings and correlating them with pathology findings in patients with a positive margin. The cancer characteristics and positive margin rate were compared between the first 90 patients and the subsequent 90 after the study was initiated (group 2). RESULTS: Of the 12 cases of positive surgical margins studied the video review helped identify 8 with a technical error. In all 4 cases in which a technical error could not be identified the positive margin site was at the distal apex. The most frequent identifiable mechanism by which positive margins occurred was a capsular tear during neurovascular bundle dissection. The 2 groups were comparable in regard to preoperative cancer characteristics and total tumor volume. In patients who underwent bilateral nerve sparing the positive margin rate was 10.6% in group 1 and 5.4% in group 2 (p = 0.18). All positive margins in group 2 involved the prostatic apex. CONCLUSIONS: Quality assurance efforts through pathological and intraoperative documentation review can help decrease the positive margin rate, particularly in organ confined disease. However, eradicating positive margins at the distal prostatic apex remains a challenge.     

Epidemiology of pericardial effusions at a large academic hospital in South Africa

The aim was to establish the prevalence of large pericardial effusions in the Western Cape Province of South Africa, and to determine the incidence of various types of effusions. A total of 233 patients presented with large pericardial effusions. Each patient underwent tests for HIV, sputum smear and culture, blood culture, blood biochemistry and serological testing. Tuberculous pericardial effusions were diagnosed according to pre-determined criteria. Eighty-four patients (36.1%) were found to be HIV positive; 81 of these (96.4 %) had tuberculous pericarditis. More than 65% of the study population was aged between 15 and 39 years. The prevalence of HIV amongst unemployed individuals was 49.0% compared to 30.0% amongst employed individuals. Tuberculous pericarditis was the most common cause of pericardial effusions (69.5%, n=162). It was concluded that tuberculosis (TB) is a leading cause of pericarditis in this province of South Africa. The prevalence of TB confounded by HIV co-infection is steadily increasing, burdening the health-care facilities.     

Effects of perfluorohexan vapor on gas exchange, respiratory mechanics, and lung histology in pigs with lung injury after endotoxin infusion

BACKGROUND: Inhaled perfluorohexan vapor has been shown to improve gas exchange and pulmonary mechanics in oleic acid- and ventilator-induced lung injury. However, in the clinical setting, lung injury frequently occurs in the context of systemic inflammation and consecutive lung injury, which may be induced experimentally by intravenous administration of endotoxin. The authors studied whether vaporized perfluorohexan is efficacious during endotoxin-induced lung injury in domestic pigs. METHODS: Twenty-two pigs (29 [23, 31] kg body weight [first, third interquartile]; tracheostomy) were anesthetized and mechanically ventilated. In the endotoxin (n = 8) and perfluorohexan groups (n = 7), we administered endotoxin of Escherichia coli 111:B4, 1 mg.kg . h for 1 h and 10 microg.kg.h for 5 h in consecutive order. In the perfluorohexan group, inhalation of the test drug was started 2 h 30 min after the start of the intravenous endotoxin and terminated after 30 min. In a control group (n=7), animals were instrumented and observed over time without further intervention. Oxygenation function was assessed from oxygen partial pressures (Po2, blood gases) and calculated shunt fraction. Respiratory compliance was calculated from airway pressure and tidal volume. Measurements were performed before and every hour during endotoxin infusion. RESULTS: After 6 h of endotoxin, gas exchange and pulmonary compliance were deteriorated in the endotoxin group (Pao2: 184 [114, 289] vs. 638 [615, 658] mmHg, pulmonary shunt fraction: 30 [23, 38] vs. 4 [3, 6]%, respiratory compliance: 12 [11, 14] vs. 22 [19, 23] ml/mbar; P < 0.05, endotoxin vs. control). Inhalation of vaporized perfluorohexan did not improve Pao 2 (107 [60, 221] mmHg), pulmonary shunt fraction (32 [26, 58]%), or respiratory compliance (14 [10, 17] ml/mbar) when compared with intravenous endotoxin (not significant, perfluorohexan vs. endotoxin). CONCLUSIONS: Inhalation of vaporized perfluorohexan does not improve pulmonary gas exchange or respiratory compliance in endotoxin-induced porcine lung injury.