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Biomedical subjects

J Bahr

Publications and source records attributed to J Bahr.

At least 19 recordsLinked to original sources

Inhibition of BCL11B expression leads to apoptosis of malignant but not normal mature T cells.

The B-cell chronic lymphocytic leukemia (CLL)/lymphoma 11B gene (BCL11B) encodes a Krüppel-like zinc-finger protein, which plays a crucial role in thymopoiesis and has been associated with hematopoietic malignancies. It was hypothesized that BCL11B may act as a tumor-suppressor gene, but its precise function has not yet been elucidated. Here, we demonstrate that the survival of human T-cell leukemia and lymphoma cell lines is critically dependent on Bcl11b. Suppression of Bcl11b by RNA interference selectively induced apoptosis in transformed T cells whereas normal mature T cells remained unaffected. The apoptosis was effected by simultaneous activation of death receptor-mediated and intrinsic apoptotic pathways, most likely as a result of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) upregulation and suppression of the Bcl-xL antiapoptotic protein. Our data indicate an antiapoptotic function of Bcl11b. The resistance of normal mature T lymphocytes to Bcl11b suppression-induced apoptosis and restricted expression pattern make it an attractive therapeutic target in T-cell malignancies.

Apoptosis↗

Outcome of cardiopulmonary resuscitation in intensive care units in a university hospital.

UNLABELLED: The purpose of this study is to evaluate the demographic characteristics of patients who suffered cardiac arrest in our intensive care units (ICUs) as well as to identify those factors influencing outcome after resuscitation following cardiac arrest. METHODS: We reviewed the records of all patients who underwent cardiopulmonary resuscitation (CPR) in our ICUs at the Georg-August University Hospital, Goettingen, Germany, from January 1, 1999 to December 31, 2003. RESULTS: One hundred and sixty-nine patients underwent CPR. Severity of illness assessed by SAPS II score on admission was 51.8+/-18.5 (predicted mortality 46.6%). The initially monitored rhythm at the time of arrest was asystole in 51 (30.2%) patients. Ventricular tachycardia/fibrillation (VT/VF) was recorded in 65 (38.5%) and pulseless electrical activity in 49 (29.0%) patients. Twenty (23.8%), 28 (33.3%) and 33 (39.3%) patients with initially recorded asystole, VT/VF and pulseless electrical activity (PEA) rhythms, respectively, survived to ICU discharge. Eighty of the 169 patients survived to hospital discharge giving a survival rate of 47.3%. The highest ICU mortality was seen in patients admitted for neurosurgery (80%) followed by major vascular surgery (77.8%), non-surgical patients (67.4%) and patients with severe sepsis (66.7%). The occurrence of cardiac arrest within the first 24h was associated with a significantly lower ICU mortality compared to a later incident. At hospital discharge 66 patients (82.5% of the survivors) achieved good cerebral recovery, 12 patients (15.0%) were severely disabled (CPC 3) while 2 (2.5%) remained unconscious. CONCLUSION: Several factors affect the outcome from CPR. However, quicker triage to ICU, closer monitoring along with prompt intervention might minimise the consequences of cardiac arrest and its complications.

Aged↗

[The new 2005 resuscitation guidelines of the European Resuscitation Council: comments and supplements].

The new CPR guidelines are based on a scientific consensus which was reached by 281 international experts. Chest compressions (100/min, 4-5 cm deep) should be performed in a ratio of 30:2 with ventilation (tidal volume 500 ml, Ti 1 s, FIO2 if possible 1.0). After a single defibrillation attempt (initially biphasic 150-200 J, monophasic 360 J, subsequently with the respective highest energy), chest compressions are initiated again immediately for 2 min. Endotracheal intubation is the gold standard; other airway devices may be employed as well depending on individual skills. Drug administration routes for adults and children: first choice IV, second choice intraosseous, third choice endobronchial [epinephrine dose 2-3x (adults) or 10x (pediatric patients) higher than IV]. Vasopressors: 1 mg epinephrine every 3-5 min IV. After the third unsuccessful defibrillation attempt amiodarone IV (300 mg); repetition (150 mg) possible. Sodium bicarbonate (1 ml/kg 8.4%) only in excessive hyperkalemia, metabolic acidosis, or intoxication with tricyclic antidepressants. Consider atropine (3 mg) and aminophylline (5 mg/kg). Thrombolysis during spontaneous circulation only in myocardial infarction or massive pulmonary embolism; during CPR only during massive pulmonary embolism. Cardiopulmonary bypass only after cardiac surgery, hypothermia or intoxication. Pediatrics: best improvement in outcome by preventing cardiocirculatory collapse. Alternate chest thumps and chest compression (infants), or abdominal compressions (>1-year-old) in foreign body airway obstruction. Initially five breaths, followed by chest compressions (100/min; approximately 1/3 of chest diameter): ventilation ratio 15:2. Treatment of potentially reversible causes (4 "Hs", "HITS": hypoxia, hypovolemia, hypo- and hyperkaliemia, hypothermia, cardiac tamponade, intoxication, thrombo-embolism, tension pneumothorax). Epinephrine 10 microg/kg IV or intraosseously, or 100 microg (endobronchially) every 3-5 min. Defibrillation (4 J/kg; monophasic oder biphasic) followed by 2 min CPR, then ECG and pulse check. Newborns: inflate the lungs with bag-valve mask ventilation. If heart rate<60/min chest compressions:ventilation ratio 3:1 (120 chest compressions/min). Postresuscitation phase: initiate mild hypothermia [32-34 degrees C for 12-24 h; slow rewarming (<0.5 degrees C/h)]. Prediction of CPR outcome is not possible at the scene; determining neurological outcome within 72 h after cardiac arrest with evoked potentials, biochemical tests and physical examination. Even during low suspicion for an acute coronary syndrome, record a prehospital 12-lead ECG. In parallel to pain therapy, aspirin (160-325 mg PO or IV) and in addition clopidogrel (300 mg PO). As antithrombin, heparin (60 IU/kg, max. 4000 IU) or enoxaparine. In ST-segment elevation myocardial infarction, define reperfusion strategy depending on duration of symptoms until PCI (prevent delay>90 min until PCI). Stroke is an emergency and needs to be treated in a stroke unit. A CT scan is the most important evaluation, MRT may replace a CT scan. After hemorrhage exclusion, thrombolysis within 3 h of symptom onset (0.9 mg/kg rt-PA IV; max 90 mg within 60 min, 10% of the entire dosage as initial bolus, no aspirin, no heparin within the first 24 h). In severe hemorrhagic shock, definite control of bleeding is the most important goal. For successful CPR of trauma patients, a minimal intravascular volume status and management of hypoxia are essential. Aggressive fluid resuscitation, hyperventilation, and excessive ventilation pressure may impair outcome in severe hemorrhagic shock. Despite bad prognosis, CPR in trauma patients may be successful in select cases. Any CPR training is better than nothing; simplification of contents and processes remains important.

Adult↗

Outcome of cardiopulmonary resuscitation in the intensive care units of a university hospital.

The purpose of this study is to evaluate the demographic characteristics of patients who suffered cardiac arrest in our ICUs and to identify those factors influencing outcome after resuscitation following cardiac arrest. We reviewed the records of all patients who underwent CPR in the two ICUs at the Georg-August University Hospital Goettingen, Germany from 1 January, 1999 to 31 December, 2003. During the study period 169 patients underwent CPR and 80 of the 169 patients survived to hospital discharge, giving a survival to hospital discharge rate of 47.3%. The initial monitored rhythm recorded at the time of arrest was asystole in 99 (58.6%) patients, ventricular tachycardia/fibrillation in 59 (34.9%) and pulseless electrical activity in 7 (4.1%) patients. The respective survival rates were 46 (54.8%), 31 (36.9%) and 5 (6.0%) to hospital discharge. Of the 80 patients that survived to hospital discharge 75 (93.8%) achieved good cerebral recovery (CPC 1 or 2) and were alert and fully oriented on discharge; 4 patients (5.0%) were severely disabled (CPC 3), while 1 (1.2%) remained unconscious and was reported dead five days after discharged to another local hospital. Illness severity as assessed by SAPS II score on admission was 38.8 +/- 16.0. None of our patients with > 40 SAPS II score 24 hours after CPR survived to be discharged from the ICU. Our study showed that nearly half the patients that had cardiac arrest in our hospital ICUs had a favourable outcome despite initial rhythms that are traditionally associated with a poor outcome. This confirms that good results are achievable in these groups of patients.

Aged↗

[To resuscitate or not? The emergency physician's decision in the prehospital setting].

OBJECTIVE: To identify factors affecting the decision to withhold resuscitative attempts or to terminate cardiopulmonary resuscitation (CPR) in the prehospital setting. METHODS: In a physician-based emergency medical system (EMS) standardised interviews with the emergency physicians were performed within 24 hours after unsuccessful or withheld CPR-efforts. RESULTS: Over a period of one year 170 prehospital cardiac arrests were evaluated. 47 patients (28 %) were declared dead on arrival by the emergency physician. The decision to withhold CPR was based on obvious clinical signs of death (32 patients) or the diagnosis of cardiac arrest due to severe trauma (8 patients). In 4 cases the terminal state of a fatal illness was the emergency physician's criterion not to initiate resuscitative efforts. In 3 patients an extended response time (more than 10 minutes) was mentioned, in combination with a primary rhythm of either asystole or electromechanical dissociation and additional information given by the family doctor. In 123 patients CPR was attempted. In 72 cases (59 %) resuscitative efforts were terminated as no return and stabilisation of spontaneous circulation was achieved. In 58 patients the decision to stop CPR was based on the evidence of cardiac death. Additional criteria for the termination of the resuscitation attempt were the duration of CPR, an extended response time, pre-existing diseases, age, pupillary status, missing brain stem reflexes, the reason of cardiac arrest, information given by the family or the family doctor and secondarily evolving signs of death. In 14 patients the emergency physicians reported that their decision to terminate CPR was primarily based on these co-factors, the evidence of cardiac death was not explicitly mentioned in these cases. CONCLUSION: In the pre-hospital setting the decision to withhold or to withdraw CPR is mostly based on reliable criteria such as obvious clinical signs of death, fatal trauma or evidence of cardiac death. Nevertheless, in a small but considerable number of cases exceptions to this rule are made by emergency physicians.

Adolescent↗

Surface and intracellular Fas expression associated with cytokine-induced apoptosis in rodent islet and insulinoma cells.

During the process of insulitis in the pathogenesis of type I (insulin-dependent) diabetes mellitus, proinflammatory cytokines induce expression of the death receptor Fas on the surface of pancreatic beta-cells and thereby contribute to the enhanced susceptibility of beta-cells for apoptosis. The aim of this study was to compare cell-surface and intracellular Fas expression associated with cytokine-induced apoptosis in commonly used beta-cell models such as isolated islets and insulinoma lines derived from mouse and rat. The cell line NIT-1 responded to the interleukin (IL)-1beta+interferon (IFN)-gamma stimulus with translocation of Fas to the cell surface. Likewise, islet cells from non-obese diabetic (NOD) mice and BB/OK rats expressed increasing amounts of the Fas receptor on their surfaces after exposure to IL-1beta in combination with IFN-gamma and tumour necrosis factor-alpha. Moreover, islets obtained from BB/OK rats at an age near the onset of diabetes had an increased surface expression of Fas compared with young rats. In contrast, western blot analysis of cell lysates from cytokine-exposed islets and insulinoma cells revealed total Fas expression levels comparable to those of untreated controls. In conclusion, islets from BB/OK rats and NOD mice, in addition to NIT-1 insulinoma cells, responded to cytokine exposure with surface expression of the Fas receptor, whereas in cell lysates the levels of expression of Fas were found to be independent of cytokine exposure. Taken together, the findings indicate that cytokine-treated beta-cells might possess two pools of Fas protein, one of which is inducible by cytokines and accounts for surface Fas expression, whereas the other is constitutively expressed in cytoplasmic compartments. The underlying mechanisms, including possible interactions between these two sources of cellular Fas expression, need to be investigated in future studies.

Animals↗

Cell surface trafficking of Fas in NIT-1 cells and dissection of surface and total Fas expression.

The appearance of Fas receptor at the surface of pancreatic beta-cells affected by progressive insulitis strongly suggests that Fas-mediated beta-cell apoptosis plays an important role in the pathogenesis of type 1 diabetes. In support of this concept, the present study has shown that islet cells from NOD mice and the beta-cell line NIT-1 respond to the proinflammatory cytokines IL-1beta and IFN-gamma with Fas surface expression in a dose- and time-dependent manner. Moreover, the prevention of cytokine-induced surface Fas expression by actinomycin D, cycloheximide, and brefeldin A demonstrated that trafficking of Fas to the beta-cell surface requires RNA and protein synthesis and, in addition is critically dependent on intracellular protein transport. Compared with total cellular Fas protein, the amount of Fas at the cell surface was relatively small and indicated that Fas is preferentially expressed in cytoplasmic compartments of NIT-1 cells. It is concluded that inflammatory insults specifically induce translocation of Fas to the beta-cell surface and that interference with cell surface Fas expression is a new strategy to improve beta-cell survival in inflamed islets.

Animals↗

Oestrogen, its receptors and function in the male reproductive tract - a review.

Oestrogen is synthesized in the male reproductive system by at least three different cell types; Sertoli, Leydig and germ cells. Although testosterone is recognized as the primary sex steroid in man, oestrogen is produced in sizable quantities in the testis, as well as the brain and is found in extremely high concentrations in the semen of several species. The high concentration of oestrogen in rete testis fluid of the rodent is now thought to be derived from the conversion of testosterone to estradiol by P450 aromatase in germ cells of the testis and spermatozoa traversing the reproductive tract. This new major source of oestrogen would target oestrogen receptors in the male reproductive tract, in particular the efferent ductules, which contain the highest concentration of oestrogen receptor-alpha. This recent data raises new hypotheses regarding the role of oestrogen in the function of the male reproductive system. The oestrogen receptor-alpha knockout mouse was used to help define the function of oestrogen in the male. It was found that oestrogen receptor-alpha is essential for fluid reabsorption in the efferent ductules and in the absence of expression the male is infertile.

Animals↗

[Attempted CPR in nursing homes - life-saving at the end of life?].

AIM: We studied the course and success rate of cardiopulmonary resuscitation (CPR) attempted on nursing home residents by a physician-staffed pre-hospital advanced cardiac life support (ACLS) team. METHODS: Ambulance records of nursing home residents from Goettingen/Germany who had a cardiac arrest were examined retrospectively. RESULTS: During a seven-year period (1992 - 1998) the ACLS team was called to 71 residents (mean age 81.8 years) who sustained cardiac arrest. In 25 patients no CPR was attempted: 20 were pronounced dead by the arriving emergency physician, though only in 7 patients obvious clinical signs of death were present. Five patients suffered from a continuous deterioration of their health status and the ACLS team arrived after the process of dying had already started. No CPR attempt was initiated. The ACLS team performed CPR on 46 nursing home residents. In 33 patients (72 % of CPR attempts) no return of spontaneous circulation (ROSC) was achieved. In three patients (6%) palpable pulse returned only transiently. Ten patients (22 %) who showed ROSC were transported to the hospital. Six patients died within 24 hours after having been admitted to the hospital, two patients within the next 8 days. Two patients survived to hospital discharge. The first was a 79-year old woman who returned to the nursing home after three weeks and survived severely mentally disabled another five days. The second was an 83-year-old man who was hospitalised for 20 days, returned in a persistent vegetative state to the nursing home and died 10 months later. A comparison of the arrest characteristics demonstrated that in patients with successful CPR there was a higher incidence of a witnessed collapse, bystander CPR, ventricular fibrillation and cardiac aetiology of arrest. CONCLUSION: In a high rate (35 %) the ACLS team with the emergency physician at the scene withheld CPR efforts in nursing home residents. Even if CPR was initiated, the benefits were very limited with only two patients (4,3 %) surviving severely disabled to hospital discharge.

Aged↗

Estrogen regulation of ion transporter messenger RNA levels in mouse efferent ductules are mediated differentially through estrogen receptor (ER) alpha and ER beta.

Earlier studies have shown that the efferent ductules (ED) of the male mouse are a target for estrogen. The loss of estrogen receptor (ER) function through either knockout technology (alpha ERKO mouse) or chemical interference (pure antagonist, ICI 182 780) results in a failure of a major function of the ED, the reabsorption of testicular fluids. The purpose of this study was to test the hypothesis that estrogen controls fluid (water) reabsorption in the ED by modulating ion transporters important for passive water movement through a leaky epithelium such as the ED. Northern blot analysis was used to detect the mRNA levels for key ion transporters in the following experimental groups: 1) wild-type (WT) control for the 14-day experiment, 2) ER alpha knockout (alpha ERKO) control for the 14-day experiment, 3) WT treated with ICI 182 780 (ICI) for 14 days, 4) alpha ERKO treated with ICI for 14 days, 5) WT control for the 35-day experiment, and 6) WT treated with ICI for 35 days. Estrogen differentially modulated the mRNA levels of key ion transporters. ER alpha mediated carbonic anhydrase II mRNA abundance, and there was a decrease in Na(+)/H(+) exchanger 3 mRNA levels in the alpha ERKO that appeared to be a cellular effect and not a direct estrogen effect. The loss of ER alpha control resulted in an increase in mRNA abundance for the catalytic subunit of Na(+)-K(+) ATPase alpha 1, whereas an increase in the mRNA abundance of the Cl(-)/HCO(3)(-) exchanger and the chloride channel cystic fibrosis transmembrane regulator was significantly ER beta mediated. Our results indicate for the first time that estrogen acting directly and indirectly through both ER alpha and ER beta probably modulates fluid reabsorption in the adult mouse ED by regulating the expression of ion transporters involved in the movement of Na(+) and Cl(-).

Animals↗

Resuscitation in Europe: a tale of five European regions.

AIM: To describe cardiac arrest data from five emergency medical services (EMS) systems in Europe with regard to survival from an out-of-hospital cardiac arrest. METHODS: Based on recommendations from various countries in Europe EMS systems were approached with regard to survival from out-of-hospital cardiac arrest. Five EMS systems were asked to report their cardiac arrest data according to the Utstein style. RESULTS: The five selected EMS systems were: Bonn (Germany), Göttingen (Germany), Helsinki (Finland), Reykjavik (Iceland) and Stavanger (Norway). For patients with a bystander witnessed arrest of cardiac aetiology the percentage of patients being discharged alive from hospital in these regions were: 21, 33, 23, 23 and 35. The corresponding percentages for patients fulfilling criteria as above and being found in ventricular fibrillation were: 32, 42, 32, 27 and 55. CONCLUSIONS: Many EMS systems in Europe show extremely good results in terms of survival after an out-of-hospital cardiac arrest. Some of the results should be interpreted with caution since they were based on relatively small sample sizes. Furthermore, the results from one of the regions (Stavanger) was unit based and not community based.

Cardiopulmonary Resuscitation↗

[Emergency and intensive care medicine as an interdisciplinary training requirement].

While substantial and practical qualification for medical practice within the framework of emergency medical services have to be proven by an advanced training, there are no special training programs for in-hospital emergency situations. As in the emergency room a transparent in-hospital emergency management has to be established including definite competencies to avoid time delays and inadequate treatment due to disputes about competence. Especially surgical intensive care medicine is an interdisciplinary task, requiring the participation of the surgeon as a responsible partner. Thus, the physician working in ICUs needs professional qualification and specialized knowledge as well as marked competence to co-operate. In any case the final clinical responsibility has to be taken over by physicians who not only have performed their internship on a ICU but are highly qualified in the whole range of intensive care medicine including all topics required in advanced intensive care medicine curricula.

Clinical Competence↗

A role for oestrogens in the male reproductive system.

Oestrogen is considered to be the 'female' hormone, whereas testosterone is considered the 'male' hormone. However, both hormones are present in both sexes. Thus sexual distinctions are not qualitative differences, but rather result from quantitative divergence in hormone concentrations and differential expressions of steroid hormone receptors. In males, oestrogen is present in low concentrations in blood, but can be extraordinarily high in semen, and as high as 250 pg ml(-1) in rete testis fluids, which is higher than serum oestradiol in the female. It is well known that male reproductive tissues express oestrogen receptors, but the role of oestrogen in male reproduction has remained unclear. Here we provide evidence of a physiological role for oestrogen in male reproductive organs. We show that oestrogen regulates the reabsorption of luminal fluid in the head of the epididymis. Disruption of this essential function causes sperm to enter the epididymis diluted, rather than concentrated, resulting in infertility. This finding raises further concern over the potential direct effects of environmental oestrogens on male reproduction and reported declines in human sperm counts.

Animals↗

The decision to terminate resuscitative efforts: results of a questionnaire.

Despite all the progress made in emergency medicine, out-of-hospital resuscitative efforts still remain unsuccessful in the majority of cases and a decision concerning termination of cardiopulmonary resuscitation (CPR) has to be made. We used a multi-question survey to assess the attitude of emergency physicians towards the duration of an unsuccessful resuscitation attempt in non-traumatic cardiac arrest, and to identify the criteria affecting the decision to terminate CPR in the prehospital setting. More than 400 physicians participated in the inquiry on CPR in adults. If spontaneous circulation cannot be restored, the majority (65%) abandon the resuscitation attempt at the latest after performing advanced cardiac life support for 45 min. The participants indicated the following factors as criteria for the termination of unsuccessful CPR: pre-existing diseases (92%), presumed interval between onset of arrest and application of CPR (92%), duration of the resuscitation attempt (90%), age of the patient (89%), electrocardiographic (ECG) alterations such as persistent asystole/ventricular fibrillation or electromechanical dissociation (83%), persistent fixed and dilated pupils (78%), lack of brain stem reflexes (31%), body temperature (12%) and suspected drug intoxication (8%). The answers reflect the physicians opinions on termination of CPR even if they do not present real decisions under emergency conditions. The results indicate that in addition to the failure to restore spontaneous circulation, other factors are involved in decision making at the scene. A high rate of respondents include criteria of weak diagnostic value such as the pupillary status, or factors of doubtful prognostic significance such as the patient's age. Concerning the patient's history and underlying diseases, the emergency physician often has to resort to presumptions. We conclude that the decision to terminate CPR is made by most physicians considering the specific circumstances of the cardiac arrest.

Adult↗

Skills of lay people in checking the carotid pulse.

American Heart Association as well as European Resuscitation Council require the carotid pulse check to determine pulselessness in an unconscious victim and to decide whether or not cardiopulmonary resuscitation (CPR) should be initiated. Recent studies on the ability of health professionals to check the carotid pulse have called this diagnostic tool in question and led to discussions. To contribute to this discussion we performed a study to evaluate skills of lay people in checking the carotid pulse. A group of 449 volunteers (most had participated in a first aid course) were asked to check the carotid pulse in a young healthy, non-obese person by counting aloud the detected pulse rate. Time intervals until correct detection of the carotid pulse were registered. Overall the volunteers needed an average of 9.46 s, ranging from 1 to 70 s. Only 47.4% of the volunteers were able to detect a pulse within 5 s, and 73.7% within 10 s. A level of 95% volunteers detecting the pulse correctly was reached only after 35 s. Based on these findings we conclude that the intervals established for carotid pulse check may be too short and that perhaps the value of pulse check within in the scope of CPR needs to be reconsidered.

Adult↗

Influence of different types of recovery positions on perfusion indices of the forearm.

BACKGROUND: Basic life support guidelines of the European Resuscitation Council (ERC) suggest a modified type of recovery position compared to that recommended by the American Heart Association (AHA). However, anecdotal reports and the results of a small study by Fulstow and Smith (Resuscitation 1993; 26: 89-91) gave evidence that the new ERC position may cause an impairment of perfusion of the lower forearm. The aim of our study was to evaluate the effects of different recovery positions on arterial perfusion and venous drainage of the forearm. METHODS: We placed 20 young healthy volunteers randomly in either ERC or AHA position for 15 min first, and in the other position thereafter. Before and between volunteers were positioned supine. In a second series 10 volunteers were positioned according to the same protocol in semiprone positions as described by Morrison, Mirkhur and Craig (MMC), and Rautek's position, respectively. Forearm perfusion indices of the dependent arm were continuously assessed by photoplethysmographic pulsatility change, photoplethysmographic volume change, invasive peripheral venous pressure and non-invasive blood pressure amplitude. Subjective discomfort was assessed non-qualitatively. RESULTS: All indices of arterial perfusion demonstrated an impairment of arterial inflow in ERC, MMC and Rautek's position as well as venous congestion in these three positions. On the contrary, AHA position was associated with no significant changes of arterial flow and only moderate, insignificant signs of venous congestion. CONCLUSION: The results of this study suggest that AHA position causes less circulatory disturbances than the ERC, MMC and Rautek's positions.

Adult↗