Annexins sense changes in intracellular pH during hypoxia

The pH(i) (intracellular pH) is an important physiological parameter which is altered during hypoxia and ischaemia, pathological conditions accompanied by a dramatic decrease in pH(i). Sensors of pH(i) include ion transport systems which control intracellular Ca2+ gradients and link changes in pH(i) to functions as diverse as proliferation and apoptosis. The annexins are a protein family characterized by Ca2+-dependent interactions with cellular membranes. Additionally, in vitro evidence points to the existence of pH-dependent, Ca(2+)-independent membrane association of several annexins. We show that hypoxia promotes the interaction of the recombinant annexin A2-S100A10 (p11) and annexin A6 with the plasma membrane. We have investigated in vivo the influence of the pH(i) on the membrane association of human annexins A1, A2, A4, A5 and A6 tagged with fluorescent proteins, and characterized this interaction for endogenous annexins present in smooth muscle and HEK (human embryonic kidney)-293 cells biochemically and by immunofluorescence microscopy. Our results show that annexin A6 and the heterotetramer A2-S100A10 (but not annexins A1, A4 and A5) interact independently of Ca2+ with the plasma membrane at pH 6.2 and 6.6. The dimerization of annexin A2 within the annexin A2-S100A10 complex is essential for the pH-dependent membrane interaction at this pH range. The pH-induced membrane binding of annexins A6 and A2-S100A10 might have consequences for their functions as membrane organizers and channel modulators.

[Integration process and organ-related fantasies in patients undergoing organ transplantation]

This review deals with an important aspect of organ transplantation, namely the process of psychic organ integration and organ-related fantasies. The body schema and body self are two important concepts in the integration of a transplanted organ. Different models and theories on organ integration are presented and will be discussed. There is evidence that beside the emotional impact and the influence on well-being, organ integration depends closely on psychic processes involving in the incorporation of the transplanted organ and the respective organ-related fantasies. Therefore, these organ fantasies - whether unconscious or conscious - may play an important role in the future development of the instinctive and highly individual relation the patients elaborate with the new organ. Beside the concern with the new organ, a bereavement to the lost old and sick organ may also influence the patients thoughts. Moreover, the good resolving of all these issues evokes the "good practice" patients develop towards the new situation. This will bring up issues as compliance, infections, rejection episodes and - most important - also organ survival.

[Changes in partner relationship after organ transplantation: comparison between heart, liver, and kidney transplantation]

AIM: This study was conducted to delineate partnership-relation functioning over time and specifically matched to various organs such as heart, liver, and kidney. METHOD: Prospective, paralleled case-control-study including patients and their respective partners before and one year after organ transplantation in 23 heart-transplant recipients, 19 liver-transplant patients, and 16 kidney-transplant recipients. To assess partnership functioning, the FB-Z (family assessment measure) of Cierpka and Frevert was used. Statistics included descriptive methods, correlations, and analysis of variance including the items "organ" and "time". RESULTS: Heart-transplant recipients and their partners show significant better overall measures in their partnership ratings (sum-value) in comparison to liver or kidney patients and their partners. In all patient and partner groups, except in kidney-transplant recipients a significant deterioration over time is discernible in the subscales role performance and emotionality. In respect to the item "organ" significant differences were found in overall functioning and the subscale communication where heart-transplant recipients and their partners have significant better functioning compared to kidney or liver transplant patients. In kidney patients and their partners only communication changes to the better in the time course. CONCLUSION: In any organ transplantation the two sides of the coin are important to bear in mind, the one is the live-saving act of transplantation as such, the other is the important distress in the phase before but equally after the operation, mainly in the first year where patients and their respective partners have to be followed and treated even in respect to psychosocial and marital functioning.

Noncompliance in organ transplant recipients: a literature review

The consequences of failing to comply to doctor's instructions can be damaging and devastating for the individual patient and their family. Noncompliance also leads to waste, as it reduces the potential benefits of therapy, and to the extra cost of treating avoidable consequent morbidity. Life-long immunosuppression is a prerequisite for good graft function, and noncompliance is often associated with late acute rejection episodes, graft loss, and death. It might be assumed that transplant patients constitute a highly motivated group, and that compliance would be high. Unfortunately, this is not the case: overall noncompliance rates vary from 20 to 50%. This overview includes literature on heart, liver, and kidney transplants in adult and pediatric transplant patients. Compliance behavior after transplantation, noncompliance and its relationship to organ loss and death, retransplantation outcome after graft loss due to noncompliance, and reasons for postoperative noncompliance will be addressed.

Solid organ transplantation: are there predictors for posttransplant noncompliance? A literature overview

BACKGROUND: Many studies confirm that noncompliance or poor compliance is one of the great problems in health care as it results in waste of resources and funds. METHODS: This overview includes literature on heart, liver, and kidney transplants with emphasis on heart transplantation in adult and pediatric transplant patients and addresses the following variables as potential predictors of postoperative compliance problems: demographic variables (age, marital status, gender) psychological variables (anxiety, denial) psychiatric disorders (major depression, anxiety, and personality disorders), poor social support, pretransplant noncompliance, obesity, substance abuse, and health-related variables (distance from transplant center, indication for transplantation, required pretransplant assist device). Relevant studies on these topics that were conducted up to 1999 are included and discussed in this overview. The most important results are presented in tables. RESULTS: Unfortunately, there has not been any systematic and comprehensive review of the literature on predictors of noncompliance in organ transplant patients so far. With organ transplantation noncompliance impairs both life quality and life span as it is a major risk factor for graft rejection episodes and is responsible for up to 25% of deaths after the initial recovery period. Therefore, it might be assumed that well-informed transplant patients are a highly motivated group whose compliance is just as high. This is not the case. However, even when graft loss means loss of life as in heart or liver transplantation, noncompliance occurs. To best select potential organ recipients, it would be ideal if patients who are very likely to show noncompliant behavior could be identified already before being transplanted. CONCLUSION: The literature overview shows the necessity of preoperative psychosocial screening regarding predictors for posttransplant noncompliance.

[Noncompliance in organ transplantation: a review]

The effectiveness of medical treatment depends not only on the appropriateness of the treatment modality but also on the patient's compliance with the intended regimen. The consequences of failing to comply can be damaging and devastating for the individual patient and his/her family. Noncompliance also leads to waste in two areas: first, a reduction of the potential benefits of therapy, and second, the additional cost of treating the avoidable consequent morbidity. A dramatic example of the consequences of noncompliance with the treatment regimen concerns patients who have had organ transplants: life-long immunosuppression is a pre-requisite for good graft function, and noncompliance is often associated with the occurrence of late acute rejection episodes, graft loss, and death. Here it might be assumed that these patients constitute a highly motivated group, and that compliance would be high. Unfortunately, this is not the case: overall noncompliance rates vary from 20 to 50%. There is no systematic and comprehensive review of the literature on noncompliance and its consequences in organ transplant patients to date. This overview includes literature on heart, liver and kidney transplants in adult and paediatric transplant patients and addresses the following issues: preoperative behaviour patterns as predictors of postoperative compliance problems, compliance behaviour after transplantation, noncompliance and its relationship to organ loss and death, retransplantation outcome after graft loss due to noncompliance, reasons for postoperative noncompliance, and ways to promote compliance.

[Knowledge, attitude and reservations of medical students about organ transplantation: results of a survey during the first year of study]

AIM: Establish a list of first year medical students' attitudes, doubts, and knowledge in the fields of organ transplantation and donation. METHOD: Anonymized questionnaire handed out to students during class lectures. RESULTS: 183 questionnaires were distributed and 117 returned (participation: 64%). The average age of the students was 21.6 +/- 2.7 years (range 18 to 38 years); the sample included 71 women (60.7%) and 48 men (39.3%). Only 2 students (2%) were not interested in the subject of organ donation. The students knew very little of the legal aspects of organ donation and 1/4 of them thought there was even a Federal law regarding organ transplantation. When asked if they knew whether a law existed in the Canton of Berne, 44% replied yes, but only 24 (20%) knew that this is contradictory. There was no gender difference in the answers to these question. From 57 students (48%) 246 individual comments on doubts and concerns were analyzed. In this respect, the students mainly questioned whether the donor was truly dead when donation took place (n = 48), if illegal transplantation could be eliminated (n = 44) and if transplantation was truly necessary (n = 43). Some also mentioned religious/ethical doubts (n = 42). In regard to organ donation by a living individual, 27 students were concerned about the health of this donor. 20 students had doubts regarding the pressure possibly applied by family members and friends and as many voiced doubts in regard to premature diagnosis of brain death of potential donors. Only 2 students were concerned about the post-mortem presentation. 45 students (48%) indicated discomfort with the donation of certain organs. They ranked the kidney as the first organ to donate, followed by the pancreas, heart, cornea, intestine, lung and liver. CONCLUSION: The interest in organ donation and transplantation is already strong in fist year medical students in the pre-clinical stage. However, differences from lay public are not readably detectable at this stage of medical training. Adequate information could influence future physicians in their mediatory role.

The accuracy of FAST in relation to grade of solid organ injuries: a retrospective analysis of 226 trauma patients with liver or splenic lesion

BACKGROUND: This study investigated the role of a negative FAST in the diagnostic and therapeutic algorithm of multiply injured patients with liver or splenic lesions. METHODS: A retrospective analysis of 226 multiply injured patients with liver or splenic lesions treated at Bern University Hospital, Switzerland. RESULTS: FAST failed to detect free fluid or organ lesions in 45 of 226 patients with spleen or liver injuries (sensitivity 80.1%). Overall specificity was 99.5%. The positive and negative predictive values were 99.4% and 83.3%. The overall likelihood ratios for a positive and negative FAST were 160.2 and 0.2. Grade III-V organ lesions were detected more frequently than grade I and II lesions. Without the additional diagnostic accuracy of a CT scan, the mean ISS of the FAST-false-negative patients would be significantly underestimated and 7 previously unsuspected intra-abdominal injuries would have been missed. CONCLUSION: FAST is an expedient tool for the primary assessment of polytraumatized patients to rule out high grade intra-abdominal injuries. However, the low overall diagnostic sensitivity of FAST may lead to underestimated injury patterns and delayed complications may occur. Hence, in hemodynamically stable patients with abdominal trauma, an early CT scan should be considered and one must be aware of the potential shortcomings of a "negative FAST".

Acute and late toxicity in prostate cancer patients treated by dose escalated intensity modulated radiation therapy and organ tracking

BACKGROUND: To report acute and late toxicity in prostate cancer patients treated by dose escalated intensity-modulated radiation therapy (IMRT) and organ tracking. METHODS: From 06/2004 to 12/2005 39 men were treated by 80 Gy IMRT along with organ tracking. Median age was 69 years, risk of recurrence was low 18%, intermediate 21% and high in 61% patients. Hormone therapy (HT) was received by 74% of patients. Toxicity was scored according to the CTC scale version 3.0. Median follow-up (FU) was 29 months. RESULTS: Acute and maximal late grade 2 gastrointestinal (GI) toxicity was 3% and 8%, late grade 2 GI toxicity dropped to 0% at the end of FU. No acute or late grade 3 GI toxicity was observed. Grade 2 and 3 pre-treatment genitourinary (GU) morbidity (PGUM) was 20% and 5%. Acute and maximal late grade 2 GU toxicity was 56% and 28% and late grade 2 GU toxicity decreased to 15% of patients at the end of FU. Acute and maximal late grade 3 GU toxicity was 8% and 3%, respectively. Decreased late > or = grade 2 GU toxicity free survival was associated with higher age (P = .025), absence of HT (P = .016) and higher PGUM (P < .001). DISCUSSION: GI toxicity rates after IMRT and organ tracking are excellent, GU toxicity rates are strongly related to PGUM.

Sexual and organ function in patients with symptomatic prolapse: are pessaries helpful?

OBJECTIVE: To evaluate quality of life and pelvic organ and sexual function before and during pessary use in patients with symptomatic pelvic organ prolapse and to determine reasons which lead to cessation of pessary use. DESIGN: Prospective observational study. SETTING: Tertiary referral center. PATIENT(S): Patients with symptomatic stage II or more prolapse of the anterior, posterior, or apical vaginal wall with or without uterus were included in this study. INTERVENTION(S): We used the Female Sexual Function Index questionnaire and the Sheffield prolapse questionnaire. For quality of life we used the King's Health Questionnaire. MAIN OUTCOME MEASURE(S): Main outcome measures were quality of life and sexual and pelvic organ function. RESULT(S): A total of 73 women participated in this study; 31 were sexually active. Desire, lubrication, and sexual satisfaction showed statistically significant improvement, and orgasm remained unchanged. Statistically significant improvement in the feeling of bulge occurred during therapy, stool outlet problems were significantly improved, overactive bladder symptoms were significantly better, and pessaries did not significantly alter incontinence. CONCLUSION(S): Pessaries have been shown to be a viable noninvasive treatment for pelvic organ prolapse improving organ and sexual function as well as general wellbeing.

Tolerance of human placental tissue to severe hypoxia and its relevance for dual ex vivo perfusion

In the dual ex vivo perfusion of an isolated human placental cotyledon it takes on average 20-30 min to set up stable perfusion circuits for the maternal and fetal vascular compartments. In vivo placental tissue of all species maintains a highly active metabolism and it continues to puzzle investigators how this tissue can survive 30 min of ischemia with more or less complete anoxia following expulsion of the organ from the uterus and do so without severe damage. There seem to be parallels between "depressed metabolism" seen in the fetus and the immature neonate in the peripartum period and survival strategies described in mammals with increased tolerance of severe hypoxia like hibernators in the state of torpor or deep sea diving turtles. Increased tolerance of hypoxia in both is explained by "partial metabolic arrest" in the sense of a temporary suspension of Kleiber's rule. Furthermore the fetus can react to major changes in surrounding oxygen tension by decreasing or increasing the rate of specific basal metabolism, providing protection against severe hypoxia as well as oxidative stress. There is some evidence that adaptive mechanisms allowing increased tolerance of severe hypoxia in the fetus or immature neonate can also be found in placental tissue, of which at least the villous portion is of fetal origin. A better understanding of the molecular details of reprogramming of fetal and placental tissues in late pregnancy may be of clinical relevance for an improved risk assessment of the individual fetus during the critical transition from intrauterine life to the outside and for the development of potential prophylactic measures against severe ante- or intrapartum hypoxia. Responses of the tissue to reperfusion deserve intensive study, since they may provide a rational basis for preventive measures against reperfusion injury and related oxidative stress. Modification of the handling of placental tissue during postpartum ischemia, and adaptation of the artificial reperfusion, may lead to an improvement of the ex vivo perfusion technique.