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Purpose: Drug-induced interstitial lung disease (DILD) is a rare, but potentially fatal toxicity. Clinical and radiological features of DILD in the early experimental setting are poorly described. Patients and Methods: A total of 2,499 consecutive patients with advanced cancer on phase I clinical trials were included. DILD was identified by a dedicated radiologist and investigators, categorized per internationally recognized radiological patterns, and graded per Common Terminology Criteria for Adverse Events (CTCAE) and the Royal Marsden Hospital (RMH) DILD score. Clinical and radiological features of DILD were analyzed. Results: Sixty patients overall (2.4%) developed DILD. Median time to onset of DILD was 63 days (range, 14–336 days). A total of 45% of patients who developed DILD were clinically asymptomatic. Incidence was highest in patients receiving drug conjugates (7.4%), followed by inhibitors of the PI3K/AKT/mTOR pathway (3.9%). The most common pattern seen was hypersensitivity pneumonitis (33.3%), followed by nonspecific interstitial pneumonia (30%), and cryptogenic organizing pneumonia (26.7%). A higher DILD score [OR, 1.47, 95% confidence interval (CI), 1.19–1.81; P < 0.001] and the pattern of DILD (OR, 5.83 for acute interstitial pneumonia; 95% CI, 0.38–90.26; P = 0.002) were significantly associated with a higher CTCAE grading. The only predictive factor for an improvement in DILD was an interruption of treatment (OR, 0.05; 95% CI, 0.01–0.35; P = 0.01). Conclusions: DILD in early-phase clinical trials is a toxicity of variable onset, with diverse clinical and radiological findings. Radiological findings precede clinical symptoms. The extent of the affected lung parenchyma, scored by the RMH DILD score, correlates with clinical presentation. Most events are low grade, and improve with treatment interruption, which should be considered early.

Recently, we found dramatic mitochondrial DNA divergence of Israeli Chamaeleo chamaeleon populations into two geographically distinct groups. We aimed to examine whether the same pattern of divergence could be found in nuclear genes. However, no genomic resource is available for any chameleon species. Here we present the first chameleon transcriptome, obtained using deep sequencing (SOLiD). Our analysis identified 164,000 sequence contigs of which 19,000 yielded unique BlastX hits. To test the efficacy of our sequencing effort, we examined whether the chameleon and other available reptilian transcriptomes harbored complete sets of genes comprising known biochemical pathways, focusing on the nDNA-encoded oxidative phosphorylation (OXPHOS) genes as a model. As a reference for the screen, we used the human 86 (including isoforms) known structural nDNA-encoded OXPHOS subunits. Analysis of 34 publicly available vertebrate transcriptomes revealed orthologs for most human OXPHOS genes. However, OXPHOS subunit COX8 (Cytochrome C oxidase subunit 8), including all its known isoforms, was consistently absent in transcriptomes of iguanian lizards, implying loss of this subunit during the radiation of this suborder. The lack of COX8 in the suborder Iguania is intriguing, since it is important for cellular respiration and ATP production. Our sequencing effort added a new resource for comparative genomic studies, and shed new light on the evolutionary dynamics of the OXPHOS system.

The mitochondrial ribosome, which translates all mitochondrial DNA (mtDNA)-encoded proteins, should be tightly regulated pre- and post-transcriptionally. Recently, we found RNA-DNA differences (RDDs) at human mitochondrial 16S (large) rRNA position 947 that were indicative of post-transcriptional modification. Here, we show that these 16S rRNA RDDs result from a 1-methyladenosine (m1A) modification introduced by TRMT61B, thus being the first vertebrate methyltransferase that modifies both tRNA and rRNAs. m1A947 is conserved in humans and all vertebrates having adenine at the corresponding mtDNA position (90% of vertebrates). However, this mtDNA base is a thymine in 10% of the vertebrates and a guanine in the 23S rRNA of 95% of bacteria, suggesting alternative evolutionary solutions. m1A, uridine, or guanine may stabilize the local structure of mitochondrial and bacterial ribosomes. Experimental assessment of genome-edited Escherichia coli showed that unmodified adenine caused impaired protein synthesis and growth. Our findings revealed a conserved mechanism of rRNA modification that has been selected instead of DNA mutations to enable proper mitochondrial ribosome function., PLoS Biology, 14 (9), ISSN:1544-9173, ISSN:1545-7885

The current article presents an analysis of the life stories of three generations of women within a family headed by a Holocaust survivor. Its uniqueness lies in its double analysis of the stories told by these women, with an interval of 12 years between telling. The first series of interviews were conducted in the early 1990s within the framework of a pioneering study in which, for the first time, three generations in each of 20 families were interviewed and their narratives analyzed. The current analyses are based on the perspective that, through life narratives, it is possible to view the transformations of relationships over time and that these transformations in relationships are central to personal development. We will examine the relationships of the women in these three generations, both with significant others and with each other. We will trace processes of development and changes in these relationships over the 12 years. Finally, we will discuss the social and methodological implications of our study.

Background: Intra-gastric band migration (band erosion) following laparoscopic adjustable gastric banding (LAGB) is a known complication requiring revisional surgery. Management has most often involved band removal and suturing of the stomach wall, followed by delayed replacement at a third operation. We report our experience with simultaneous band removal and replacement. Methods: Between May 2001 and December 2003, we performed 754 laparoscopic operations using the Lap-Band ®. Patients developing band erosion were treated by laparoscopic band removal and immediate replacement of a new band following gastric wall repair. Results: 16 patients (2.1%) developed band erosion after a mean of 23 months following surgery (range 11-40 months). Patients presented with epigastric pain (6), port-site bulge (3) or were asymptomatic (7), band erosion being suspected during fluoroscopy for band adjustment and confirmed by gastroscopy. Postoperatively, 11 patients developed fever that responded to antibiotics. No patient suffered from intra-abdominal infection, wound infection, pneumonia or pulmonary embolism. Mean hospital stay was 4 days (range 1-8 days). Conclusion: Band erosion following LAGB can be treated safely with simultaneous laparoscopic band removal, gastric wall suturing and immediate replacement of the band, thereby preventing weight gain, the appearance of co-morbidities and the need for additional surgery.

In spite of the fact that the A-bombings of Hiroshima and Nagasaki occurred nearly 60 years ago, there has been very little psychosocial research on the long-term effects of these unprecedented nuclear attacks on its victims. In this qualitative study, we use psychosocial literature from the Holocaust in order to help understand the effects of this man-made tragedy. We analyzed semi-structured interviews taken with 8 survivors of the bombs--5 from Nagasaki and 3 from Hiroshima. Our research questions were: When the survivors talk about their experiences, what do they focus on and with what are they preoccupied? What can we learn about the long-term effects of the experiences from both psychological and physical aspects? And, where does the A-bomb experience "fit" into the survivors' lives? Our analyses showed that there were 9 main themes that emerged from the interviews that could be grouped into two main categories--themes connected to the experience itself and themes connected to life afterward. We discuss the implications of these themes on the personal, social, and cultural levels and offer suggestions concerning ideas for dealing with the trauma.

RNA transcripts are generally identical to the underlying DNA sequences. Nevertheless, RNA–DNA differences (RDDs) were found in the nuclear human genome and in plants and animals but not in human mitochondria. Here, by deep sequencing of human mitochondrial DNA (mtDNA) and RNA, we identified three RDD sites at mtDNA positions 295 (C-to-U), 13710 (A-to-U, A-to-G), and 2617 (A-to-U, A-to-G). Position 2617, within the 16S rRNA, harbored the most prevalent RDDs (>30% A-to-U and ∼15% A-to-G of the reads in all tested samples). The 2617 RDDs appeared already at the precursor polycistrone mitochondrial transcript. By using traditional Sanger sequencing, we identified the A-to-U RDD in six different cell lines and representative primates (Gorilla gorilla, Pongo pigmaeus, and Macaca mulatta), suggesting conservation of the mechanism generating such RDD. Phylogenetic analysis of more than 1700 vertebrate mtDNA sequences supported a thymine as the primate ancestral allele at position 2617, suggesting that the 2617 RDD recapitulates the ancestral 16S rRNA. Modeling U or G (the RDDs) at position 2617 stabilized the large ribosomal subunit structure in contrast to destabilization by an A (the pre-RDDs). Hence, these mitochondrial RDDs are likely functional.

The present study tests stages in the ability of some children of perpetrators of the Holocaust in Germany to work through emotional and moral issues regarding their fathers' perpetrating role during the Third Reich. The following questions are raised: Did they try to distance themselves by playing down the Holocaust and the moral meaning of their fathers' involvement in it? Did any children try to work through issues relating to their fathers' impaired morality? Did any children successfully reach the stage of integration? Fifty-seven persons were contacted by the author between September 1985 and June 1987, of whom 9 refused to be interviewed. Thirty interviewees were children whose fathers had taken an active part in the implementation of the euthanasia program, in the Einsatzgruppen, in the extermination camps or in related activities. The fathers of the remaining 18 interviewees were affiliated with SS units at times and in places where the atrocities took place, but what they actually did or did not do was not proven. In general, there was an almost total silencing of accounts of the extermination process in homes and schools. Acknowledgment, if any, of the atrocities appeared through accounts of trials and friends and in newspapers or, only recently, through the children's active searching. When children who learned what their father-perpetrator had done during the war also came to understand the moral implications, they usually experienced severe emotional conflict, which they had to confront on their own. Only a few succeeded in walking across a very narrow bridge to a working through of the related issues and emotions. The implications of the present analysis for future research on the prevention and outcomes of genocide are discussed.

Children with asthma or failure to thrive (FTT) are frequently referred for the quantitative pilocarpine iontophoresis sweat test (QPIT) for diagnosing cystic fibrosis (CF). The aim of our study was to compare the prevalences of asthma and FTT among patients with a confirmed diagnosis of CF. Two-hundred and fifty-five children, who were referred for QPIT between 1991-1996 in order to rule out CF were studied retrospectively. All sweat samples had been obtained and analyzed according to the National Committee For Clinical Laboratory Standards. Asthma was defined as 24 episodes of wheezing, treated successfully by inhaled bronchodilators. Failure to thrive was was defined by either a weight below the 5th precentile or crossing of 2 major precentiles in 1 year. The prevalence of asthma was significantly higher than that of FTT among the cohort study (28.6% vs. 7.1% as a single indication, and 36.5% vs. 7.9% when combined with other indications). The prevalence of CF among patients with FTT was higher than among asthmatic patients (5.2% vs. 3%, p = 0.06). Not one patient diagnosed as having CF was referred to a sweat test only because of asthma. As a single presentation, the diagnostic yield of asthma seems to be poor, compared to FTT. However, further, larger-scale studies should be conducted on this issue.

Peritoneal dialysis is a widely accepted route for renal replacement. With the advent of endoscopy, many surgical techniques for the prevention of catheter failure have been proposed.To evaluate the outcomes of patients undergoing laparoscopic Tenckhoff catheter implantation using the pelvic fixation technique.Data analysis was retrospective. All procedures were performed under general anesthesia. A double-cuffed catheter was inserted using two 5 mm trocars and one 10 mm trocar, fixing its internal tip to the dome of the bladder and its inner cuff to the fascia. Catheter failure was defined as persistent peritonitis/exit-site/tunnel infection, severe dialysate leak, migration or outflow obstruction.LTCI was performed in 34 patients. Mean patient age was 65 +/- 17 years. In 12 of the 34 patients the indication for LTCI was end-stage renal failure combined with NYHA class IV congestive heart failure. Operative time was 35 +/- 15 minutes. A previous laparotomy was performed in 9 patients. Hospital stay was 1.5 +/- 0.6 days. The first continuous ambulatory peritoneal dialysis was performed after 20 +/- 12 days. Median follow-up time was 13 months. There were several complications, including 5 (14%) exit-site/tunnel infections, 27 episodes (0.05 per patient-month) of bacterial peritonitis, 3 (9%) incisional hernias, 1 case of fatal intraabdominal bleeding, 2 (5.8%) catheter migrations (functionally significant), and 10 (30%) cases of catheter plugging, 8 of which were treated successfully by instillation of urokinase and 2 surgically. A complication-mandated surgery was performed in 8 patients (23.5%). The 1 year failure-free rate of the catheter was 80.8%. One fatal intraabdominal bleeding was recorded.LTCI is safe, obviating the need for laparotomy in high risk patients. Catheter fixation to the bladder may prevent common mechanical failures.

Acute portal vein thrombosis (PVT) is a devastating complication of Budd-Chiari syndrome (BCS). Con-servative approach, anticoagulation, systemic or transarterial thrombolysis, and urgent liver transplanta-tion were applied in this scenario but with poor results. We present and discuss an approach to treat BCS complicated by acute PVT. Two young female patients presented with acute liver failure, rapidly pro-gressive tense ascites, renal- and respiratory failure. The diagnosis of chronic BCS complicated by acute PVT was confirmed with ultrasound Doppler. Initial treatment was supportive. Right portal vein local-ization was by transarterial portogram or by computed tomography-guided microcoil placement. Trans-jugular intrahepatic portosystemic shunt (TIPS) was performed and included Wallstents and a Jograft in one case and Viatorr stentgraft that was extended later with a Hemobahn stentgraft in another. Mechan-ical clot removal from the portal system was performed in the primary procedure and in a revision pro-cedure in the following few days. Stents were placed precisely with no extension into the inferior vena cava or deeply into the main portal vein. Patients were fully anticoagulated and patency was assessed by ultrasound Doppler. The procedures were performed on days 5 and 10 following admission. In both cases, successful thrombectomies were reveised and maintained. Partial occlusion of the TIPS and reaccumulation of ascites were reversed with repeated procedure. Both patients were discharged without ascites and normal liver function. In conclusion, urgent TIPS and portal vein thrombectomy via TIPS are emerging therapeutic options that offer a safe and effective treatment to patients with BCS complicated by acute portal vein thrombosis.

During the years 1831-1918 Israel (Palestine at that time) suffered from repeated cholera epidemics. The cholera epidemics were the major cause of severe health crisis among the population. The epidemics were transmitted by returening pilgrims returning from Mecca and, during the first world War, by the Turkish soldiers crossing the country. The disease caused panic amongst the population due to its high mortality rate. Quarantine which was the major measure taken by the government at that time was repeatedly broken by people trying to escape from the affected area. During the epidemic of 1902, patients were even reluctant to be treated by physicians as they were blamed for causing death. On the other hand, cholera was a major trigger for maintaining a better sanitation and establishing social relief systems within the communities. Most of the epidemics occurred in the old cities such as Jerusalem, Tiberia and Jaffa where infrastructure was inadequate. Cholera outbreaks were the trigger to build outside the old cities as in case of Jerusalem in which after the 1865 outbreak the city was expanded outside the walls. Since the end of the Ottoman period in Israel, cholera epidemics ceased, and except for very small occeasional small outbreaks, cholera is not seen here more.

The prevalence of morbid obesity is increasing steadily among women of reproductive age. In addition to the well-known comorbidities of the disease, it has been shown that the pregnancy outcome for obese women is worse than for women with a normal body mass index. This study aimed to evaluate the pregnancy and perinatal outcomes for women who underwent laparoscopic adjustable gastric banding (LAGB) because of morbid obesity.This prospective, population-based study was conducted in a general surgery clinic of a tertiary hospital serving as a referral center for bariatric operations. All the patients underwent LAGB by the pars flaccida technique. A database containing information regarding age, pre- and postoperative weight and body mass index, weight gain, and LAGB-related or -unrelated complications during pregnancy was constructed for all women of childbearing age who underwent LAGB. A questionnaire was designed to provide perinatal data concerning both mother and neonate.The 74 women enrolled in this study had 81 single tone pregnancies. Their body mass index decreased significantly after LAGB, from 43.3 +/- 5.8 to 30.3 +/- 3 kg/m2 at conception (p0.0001). The average time to the first live birth after surgery was 27 +/- 3 months. Band slippage was diagnosed and treated laparoscopically in two patients (2.4%). Weight gain during pregnancy was 10.6 +/- 2.1 kg. The rates of pregnancy-induced hypertension and gestational diabetes were 7.4% and 16% of all pregnancies, respectively. In 17 cases (20%), cesarean section was performed. Delivery occurred after 39.1 weeks of gestation. The mean birth weight was 3.09 +/- 0.5 kg. Major congenital anomalies, postnatal hypoglycemia, symptomatic polycythemia or neonatal death were not recorded.The findings show that LAGB is safe for both mother and newborn during gestation and delivery.

Study objective: To evaluate the contribution of flexible fiberoptic bronchoscopy (FFB) and BAL to the clinical management of patients in a pediatric ICU (PICU). Setting and design: A retrospective study based on medical records in a six-bed pediatric ICU of a tertiary care children's hospital serving as a referral center for airway surgery. Patients and participants: One hundred consecutive infants and children hospitalized in a PICU, who underwent FFB with or without BAL. Measurements and results: One hundred fifty-five procedures were performed, for the following causes: search for airways anatomic pathologies (114 of 155 procedures, 74%), including 55 procedures during the perioperative period of airway surgery; treatment of atelectasis (35 of 155 procedures, 22.5%); and BAL (30 of 155 procedures, 19%). Thirty-five percent of procedures had more than one cause. Airway pathology was observed in 79 of 114 procedures (69%). Management changed from conservative to surgical in 44 of 114 procedures (39%). In airway surgery cases, reoperation subsequent to postoperative FFB took place in 35%. BAL results changed antimicrobial treatment in 15 of 30 cases, with clinical improvement in 10 of 30 cases (33%). Treatment of atelectasis was successful in 26 of 35 cases (74.3%). No procedure-related mortality, life-threatening complications, or significant changes in patient status occurred. Conclusions: FFB is an important and safe procedure in very sick infants and children with a variety of respiratory diseases, and significantly contributes to their management. FFB should be considered to be a PICU staff expertise.

The undiscussible within daily discourse can have intentional and unintentional forms. The first occurs when someone intentionally gears the discourse so that it will not reveal certain facts which have happened (such as being an abused child, or a perpetrator during the Holocaust). We assume that even if they were difficult to reconstruct as part of one's biography, these facts could be verified externally (not only through the feelings of the victim). In the first part of the paper, we analyze the paradoxical nature of such discourse, and show how difficult it is to work through intentional undiscussibility. In the second part, we discuss what happens when the undiscussible facts can not be verified, meaning that there is doubt if events have taken place. By presenting a case study of a German woman who tried to construct a biography in face of certain undiscussibility in her family, we discuss the different social reactions evolving in such reconstruction of feeling-facts. We thereby hope to confront the psychoanalytic approach to narrative analysis with the constructivist hermeneutic one.

Ninety-eight men aged

In 1980, 87 male patients (age range 34–60 years), hospitalized after their first myocardial infarction (MI), were asked why they believed they got the infarct and what would help them cope with it. In a multiple regression analysis, their causal attributions accounted for 15% of the explained variance in their physical, sexual, social and work functioning after 6 and 18 months, their level of education accounted for 25% and the severity of their infarct for 10%. This result was replicated in a cross-cultural study. A follow-up study shows that 12 years after the MI, the patients' initial causal attributions still accounted for part of their reliabilitation and life expectancy. Of the original 87, 23 had died between 1980–1992 from cardiac causes and 50 male patients were located and re-interviewed at the Soroka ICCU, in 1992. This suggests a very low-risk post-MI sample. The only risk-factor, accounting for the difference between the surviving and the deceased patients, was the initial obesity of the latter. The functional capacity outcome of the survivors was accounted for by their age (24%) and initial causal attributions (26%). Also the initial causal attributions (5%) still accounted for the subjective perception of functioning among the survivors. These results suggest that the initial causal attributions may have created positive or negative self-fulfilling prophecies which liad long-term consequences, especially in a low-risk, post-MI population, in which risk factors hardly effected long-term prognosis.

Objective To predict how much blood will be needed based on the number of injured patients arriving after a multiple-casualty incident. Design A retrospective study evaluating data collected in 18 consecutive terrorist attacks in the city of Tel Aviv between January 1997 and February 2005. Setting A large, urban trauma center. Patients A total of 986 patients in 18 events. Main Outcome Measures Number of packed red blood cell (PRBC) units transfused per patient. Results A total of 332 U of PRBCs were transfused. Half of the PRBC units were administered as massive transfusions to 4.7% of the patients. The number of PRBC units transfused per patient index (PPI) was related to incident size (mean [SD], 0.70 [1.60] to 1.50 [1.60]). The most frequent major blood group transfused was type O (50%). Half of the units of PRBCs were supplied during the first 2 hours. Conclusions One unit of blood per evacuated victim is sufficient in a small multiple-casualty incident and 2 U is sufficient in a large multiple-casualty incident. Half of the PRBC units should be blood group O.