The checkpointkinase 2 (CHK2) 1100delC germ line mutation is not associated with the development of squamous cell carcinoma of the head and neck (SCCHN)

Background  

The checkpointkinase 2 (CHK2) is part of the highly conserved ATM-CHK2 signaling pathway, which is activated in response to DNA damage, in particular after double strand breaks which can be caused by carcinogens like smoking. After induction of downstream targets, e.g. the tumor suppressor p53, its activation leads to cell cycle arrest and apoptosis. Recently, the presence of CHK2 germ line mutations, primarily the 1100delC variant, has been reported to be involved in carcinogenesis. The CHK2 1100delC variant results in a truncated protein which is instable and inactive. Carriers of this variant have been shown to have an increased risk to develop breast cancer and probably also other tumors. Our purpose was to investigate the role of CHK2 germ line mutations in patients with squamous cell carcinoma of the head and neck (SCCHN).     

Comparison of the Diskus inhaler and the Handihaler regarding preference and ease of use.

Many chronic obstructive pulmonary disease (COPD) patients use their inhaler ineffectively and there is a trend towards increased inhaler resistance. We wanted to answer two questions: Is there a difference in preference and ease of use between Diskus (DK) and Handihaler (HH)? How acceptable are inhalation resistances? Sixty COPD patients, naive to DK and HH, but experienced in the use of other inhalers, had to read the instruction leaflet and demonstrate their inhalation technique. If errors were made, instruction was given and inhalation technique was checked again. Patients had to state a preference for DK or HH. Subsequently they inhaled through a range of resistances and scored the acceptability. There was no difference in the number of instructions needed for both inhalers. One third inhaled perfectly after reading the instruction leaflet, which increased to 85% after one instruction. More patients preferred the DK (43) than the HH (16). With decreasing resistance acceptability increases, but it reaches a plateau. Patients have a clear preference for the DK. There is no difference in the number of instructions needed to obtain a perfect inhalation technique, but for some patients one instruction is not enough. The trend to increase the resistance of inhalers has reached a critical point with regard to acceptability.     

Prognostic factors and results after surgical treatment of idiopathic macular holes, stage 2 and 3

PURPOSE: To determine prognostic factors, functional outcome and subjective rating after surgery for macular holes stage 2 and 3. METHODS: We studied 53 eyes of 49 patients undergoing vitreous surgery for macular holes stage 2 (46%) and 3 (54%). Mean follow-op was 114 weeks (32-204, std.dev. +/- 48), mean age 68.9 years (44-89, std.dev. +/- 6.8). 72% were female, 11% were pseudophakic, 19% phakic, 70% had a combined procedure (pars plana vitrectomy, phacoemulsification and IOL). Surgery consisted in a pars plana vitrectomy, peeling of epiretinal membranes and ILM, internal tamponade with SF6 (98%) resp. Si-oil in one case. Patients had to keep face-down position 6 x 20 minutes per day. RESULTS: The hole was completely closed in 90.6%. Anatomical failures included, 86% had an increase of VA, 41% = 5 lines (Final VA median 20/30, max. 20/20). No further increase of the retinal function occurred after 6 months. The visual result did not correlate with the duration of symptoms. 84% were satisfied with the outcome, subjective rating was not correlated with final VA or change of VA. 19% showed postoperative typical peripheral visual field defects. Visual field loss was not correlated with perioperative IOP elevation. CONCLUSION: Macular hole surgery has a high functional success rate. Postoperative visual field defects are an important problem.     

Vertical diplopia after cataract operation

PURPOSE: Presentation and analysis of patients with vertical diplopia appearing after cataract surgery in retrobulbar anesthesia. SUBJECTS AND METHODS: Between 1990 and 1998 9 Patients with vertical diplopia following cataract surgery in retrobulbar anesthesia were studied in our Orthoptic Department. Each patient had complete orthoptic examination with Hess-screen-test. Additionally, some patients underwent neuroradiologic imaging and forced-duction testing. RESULTS: We subdivided the patients in a group of 4 patients with hypertropia and of 5 patients with hypotropia of the operated eye. All hypotropias were left-sided. Seven patients showed an overaction of the involved muscle without regression. Seven patients underwent surgery of a vertical muscle. Only 1 patient needed prismatic therapy postoperatively. The other 2 non-operated patients were satisfied with prisms alone. CONCLUSIONS: The proposed pathogenesis of vertical diplopia in these cases is fibrosis and contracture of the injured muscle, which could be due to anesthetic myotoxicity after direct injection into the muscle or to an intramuscular hemorrhage. On the other hand hypertropia could be a result of placement of bridle sutures. We discuss prevention and therapy of such complications.     

Mechanisms of action of arsenic trioxide

Arsenic trioxide has shown substantial efficacy in treating both newly diagnosed and relapsed patients with acute promyelocytic leukemia (APL). As a single agent, it induces complete remissions, causing few adverse effects and only minimal myelosuppression. These successes have prompted investigations to elucidate the mechanisms of action underlying these clinical responses. Substantial data show that arsenic trioxide produces remissions in patients with APL at least in part through a mechanism that results in the degradation of the aberrant PML-retinoic acid receptor alpha fusion protein. Studies have also investigated concerns about the toxicity and potential carcinogenicity of long-term exposure to environmental arsenic. Arsenic apparently affects numerous intracellular signal transduction pathways and causes many alterations in cellular function. These actions of arsenic may result in the induction of apoptosis, the inhibition of growth and angiogenesis, and the promotion of differentiation. Such effects have been observed in cultured cell lines and animal models, as well as clinical studies. Because arsenic affects so many cellular and physiological pathways, a wide variety of malignancies, including both hematologic cancer and solid tumors derived from several tissue types, may be susceptible to therapy with arsenic trioxide. These multiple actions of arsenic trioxide also highlight the need for additional mechanistic studies to determine which actions mediate the diverse biological effects of this agent. This information will be critical to realizing the potential for synergy between arsenic trioxide and other chemotherapeutic agents, thus providing enhanced benefit in cancer therapy.     

Involvement of polyamines in apoptosis. Facts and controversies: effectors or protectors?

The natural polyamines (putrescine, spermidine and spermine) are ubiquitous low-molecular aliphatic amines that play multifunctional roles in cell growth and differentiation. Recently, evidence has merging that polyamines are actively involved in cell death. Changes in polyamine homeostasis have been reported during cell death of nerve cells, in programmed cell death of embryonic cells and in various in vitro models of apoptosis. Polyamines and many of their structural analogs exert cytotoxic effects in vitro as well in vivo. Furthermore, polyamine analogs and inhibitors of the polyamine anabolic/catabolic pathways modulate processes of cell death in a cell-type specific way. Much ambiguity exists in the working mechanisms by which polyamines mediate apoptosis since they have been shown to act as promoting, modulating or protective agents in apoptosis. Nevertheless, from the studies reviewed here it can be concluded that polyamines are critically involved in cellular survival which makes them suitable targets for therapeutic intervention that is specifically directed to cell death pathways.     

Mutational analysis of the BRAF gene in human congenital and dysplastic melanocytic naevi

Eighteen congenital melanocytic naevi (CMN) from 17 patients and 18 dysplastic melanocytic naevi (DMN) from 18 patients were screened for mutations in the BRAF oncogene (present study) and the N-ras oncogene (in the course of two foregoing studies) by single-strand conformational polymorphism (SSCP)/sequencing analysis. BRAF mutations were demonstrated in both types of lesion. As a whole, 17 of 18 CMN (94.4%) and five of 18 DMN (27.7%) harboured either BRAF or N-ras mutations. As the BRAF oncogene is frequently found to be mutated in human cutaneous melanomas, it may constitute a risk factor for melanoma formation within CMN and DMN.     

Mutational analysis of 9 different tumour-associated genes in human malignant mesothelioma cell lines

Seven tumour suppressor genes (Chk1, Chk2, Apaf1, Rb1, p53, p16(INK4a) and p14(ARF)) and two oncogenes (N-ras and BRAF) were screened in nine human malignant melanoma (HMM) cell lines for point mutations or small deletions/insertions by DGGE, TGGE and SCCP analysis. For the first time in human mesothelioma, Chk1 gene mutations were detected in two of the nine investigated HMM cell lines. P53 gene mutations were found in three cell lines and p16(INK4a) mutations in 5. Mutation of the Chk1 gene implies a novel disruption mechanism of the p53 pathway in HMM, without affecting p53 itself. According to our knowledge, this is the first mutation screening of Chk1, Chk2, Apaf1 and Rb1 in human malignant mesothelioma.     

Communication during trauma resuscitation: do we know what is happening?

OBJECTIVE: Verbal communication is essential for teamwork and leadership in high-intensity performances like trauma resuscitation. We evaluated communication during multidisciplinary trauma resuscitation. METHODS: The main trauma room of a level one trauma centre was equipped with a digital video recording system. Resuscitations were consecutively and prospectively enrolled. Patients with revised trauma score (RTS)=12 were resuscitated by a 'minor trauma team' and patients with RTS<12 by a 'major trauma team'. Information transferral from physicians to other team members was evaluated separately for all ABCDE's, according to initiation, audibility and response. The observer was trained and the first 30 video's were excluded. RESULTS: From May 1st to September 1st 2003, 205 resuscitations were included, 12 were lost for evaluation. The 'major trauma team' resuscitated 74 patients (ISS:21.4). Communication was audible in 56% and understandable in 44% during the primary survey. The 'minor trauma team' assessed 119 patients (ISS:7.4). Communication was audible in 43% and understandable in 33%. CONCLUSIONS: Communication during trauma resuscitation was found to be sub optimal. This is potentially harmful for trauma victims. Professionals and institutions should be aware that communication is not self-evident. Introduction of an aviation-like communication feedback system could help to optimise trauma care.