[Taxus poisoning: an unusual cause of acute heart failure]. / Das Gift der Eibe: eine ungewöhnliche Ursache der akuten Herzinsuffizienz.

Taxines are the active, poisonous constituents in yew plants (Taxus spp.) and can result in life-threatening cardiac toxicity. Rapid elimination of yew plant material and administration of active charcoal can limit absorption of toxins. Treatment is confined to supportive care. Therapeutic interventions such as utilization of digoxin immune fab, hemodialysis and temporary cardiac pacing may be utilized. Extracorporeal life support should be considered for severe cases.

[Venoarterial extracorporeal membrane oxygenation for out-of-hospital cardiac arrest. Case series of prehospital and in-hospital therapies]. / Venoarterielle extrakorporale Membranoxygenierung beim präklinischen Herz-Kreislauf-Stillstand. Fallserie prä- und innerklinischer Behandlungen.

Despite new concepts and strategies of basic and advanced life support, the outcome of patients with out-of-hospital cardiac arrest (OHCA) remains poor. The main reason accounting for these poor results is a low-flow phase during conventional cardiopulmonary resuscitation (CPR) with insufficient end organ perfusion. The early use of venoarterial extracorporeal membrane oxygenation (vaECMO) during CPR, i.e. extracorporeal resuscitation (ECPR) might improve OHCA survival rates as well as the neurological outcome in resuscitated patients. This article on a case series discusses the management of ECPR in three patients with OHCA. All patients suffered from a witnessed OHCA and received effective bystander CPR. After subsequent advanced cardiac life support could not achieve a return of spontaneous circulation (ROSC), vaECMO support was established as a bridge to therapy on site or after transportation to a primary or tertiary hospital. During the course of therapy two patients died and one patient was discharged after a full recovery. Early ECPR might improve the outcome in patients with prolonged cardiac arrest without ROSC. The use of ECPR should be based on the individual decision of an experienced ECPR team considering defined inclusion and exclusion criteria. As the outcome mainly depends on the duration and quality of conventional CPR, ECPR support should be requested immediately after establishing advanced life support (approximately 10-15 min).

[Obesity and heart failure]. / Adipositas und Herzinsuffizienz.

BACKGROUND: Obesity is an important risk factor for the development of heart failure. DIAGNOSTICS: In normotensive obese patients, a reduced peripheral resistance is typically observed and is accompanied by an increased fluid volume and an increase in cardiac work, resulting in hypertrophy and diastolic heart failure, which can be visualized with echocardiography. However, in the presence of arterial hypertension cardiac geometry is not different to hypertensive heart disease without obesity. Furthermore, the typical changes found with obesity, such as reduced peripheral resistance and increased blood volume, are no longer present. Obstructive sleep apnea (OSA) is very common in obesity and warrants screening but levels of the heart failure marker N-terminal pro-brain natriuretic peptide (NT-ProBNP) might be misleading as the values are lower in obesity than in normal weight controls. THERAPY: Body weight reduction is advisable but difficult to achieve and much more difficult to maintain. Furthermore, diet and exercise has not been proven to enhance life expectancy in obesity. However, with bariatric surgery, long-term weight reduction can be achieved and mortality can be reduced. CONCLUSIONS: With effective weight loss and improved clinical outcome after bariatric surgery, treatment of obesity has shifted much more into focus. Regardless of technical challenges in the work-up of obese patients, clinical symptoms suggestive of cardiac disorders warrant prompt investigation with standard techniques following recommendations as established for normal weight patients.

Knockdown of the gene encoding Drosophila tribbles homologue 3 (Trib3) improves insulin sensitivity through peroxisome proliferator-activated receptor-γ (PPAR-γ) activation in a rat model of insulin resistance.

AIMS/HYPOTHESIS: Insulin action is purportedly modulated by Drosophila tribbles homologue 3 (TRIB3), which in vitro prevents thymoma viral proto-oncogene (AKT) and peroxisome proliferator-activated receptor-γ (PPAR-γ) activation. However, the physiological impact of TRIB3 action in vivo remains controversial. METHODS: We investigated the role of TRIB3 in rats treated with either a control or Trib3 antisense oligonucleotide (ASO). Tissue-specific insulin sensitivity was assessed in vivo using a euglycaemic-hyperinsulinaemic clamp. A separate group was treated with the PPAR-γ antagonist bisphenol-A-diglycidyl ether (BADGE) to assess the role of PPAR-γ in mediating the response to Trib3 ASO. RESULTS: Trib3 ASO treatment specifically reduced Trib3 expression by 70% to 80% in liver and white adipose tissue. Fasting plasma glucose, insulin concentrations and basal rate of endogenous glucose production were unchanged. However, Trib3 ASO increased insulin-stimulated whole-body glucose uptake by ~50% during the euglycaemic-hyperinsulinaemic clamp. This was attributable to improved skeletal muscle glucose uptake. Despite the reduction of Trib3 expression, AKT2 activity was not increased. Trib3 ASO increased white adipose tissue mass by 70% and expression of Ppar-γ and its key target genes, raising the possibility that Trib3 ASO improves insulin sensitivity primarily in a PPAR-γ-dependent manner. Co-treatment with BADGE blunted the expansion of white adipose tissue and abrogated the insulin-sensitising effects of Trib3 ASO. Finally, Trib3 ASO also increased plasma HDL-cholesterol, a change that persisted with BADGE co-treatment. CONCLUSIONS/INTERPRETATION: These data suggest that TRIB3 inhibition improves insulin sensitivity in vivo primarily in a PPAR-γ-dependent manner and without any change in AKT2 activity.

Prevention of hypertensive crises in rats induced by acute and chronic norepinephrine excess.

Calcium Channel Blockers (CCBs), competitive α-adrenoceptor blockers, and phenoxybenzamine (POB) are used for preoperative treatment of pheochromocytomas. We analyzed the protection from hypertensive crisis provided by these drugs during acute and chronic norepinephrine excess. To ensure adaptive changes during chronic norepinephrine (NE) excess, we continuously exposed male Wistar rats to NE for 3 weeks (osmotic pumps). Afterwards, blood pressure (BP) was continuously measured while NE boli (0-1000 µg/kg, i. v.) were administered before and after antihypertensive treatment in anesthetized and catheterized rats. A single dose of urapidil (10 mg/kg), nitrendipine (600 µg/kg) and POB (10 mg/kg) lowered BP from 212 ± 12 mmHg by 52 ± 7%, 31 ± 9%, and 50 ± 6%, respectively. With NE boli a maximum BP of 235 ± 29, 240 ± 30 and 138 ± 3 mmHg was measured in urapidil, nitrendipine, and POB treated animals (p<0.05). The number of hypertensive episodes (delta BP >30 mmHg) was 3 (3), 1.5 (0-3), and 0 (0-1) (p<0.05). Because of inferiority, urapidil was excluded from further testing. Chronically NE exposed rats were treated with POB (10 mg/kg/d), nifedipine (10 mg/kg/d), or vehicle for 7 days. Marked BP elevations were observed at baseline (167 ± 7, 210 ± 7 , and 217 ± 7 mmHg, p<0.01) and maximum blood pressure was 220 ± 32, 282 ± 26, and 268 ± 40 mmHg (p<0.001) with NE boli. Further stabilization was achieved combining POB pretreatment with a continuous nifedipine infusion, which effectively prevented BP elevations during NE excess. POB was the most effective drug used in monotherapy, but BP stabilization was superior using a combination of POB pretreatment with a continuous nifedipine infusion in this model.

Measurement of end-expiratory lung volume by oxygen washin-washout in controlled and assisted mechanically ventilated patients.

OBJECTIVE: Assessing limits of agreement with helium dilution and repeatability of a new system (lung funcution, LUFU) that measures end-expiratory lung volume (EELV) in mechanically ventilated patients using the O(2) washin (EELV(Win)) and washout (EELV(Wout)) technique. LUFU consists of an Evita 4 ventilator, a side-stream oxygen analyzer, and a dedicated PC software. DESIGN AND SETTING: Prospective human study in a general ICU of a University hospital. PATIENTS: Thirty-six mechanically ventilated patients. INTERVENTIONS: We obtained 36 couples of both EELV(Win) and EELV(Wout) measurements in each patient (5 with healthy lungs, 9 with ALI, 22 with ARDS). Measurements were obtained with patients ventilated either by assisted (ASB, 16 measurements) or controlled (CMV, 20 measurements) ventilation. In 19 of 20 cases in CMV, we obtained helium dilution measurements (EELV(He)). MEASUREMENTS AND RESULTS: Bias for agreement with EELV(He) was -16 +/- 156 and 8 +/- 161 ml, respectively, for EELV(Win) and EELV(Wout). Bias for agreement between EELV(Win) and EELV(Wout) was 28 +/- 78 and 23 +/- 168 ml, respectively, for CMV and ASB. During CMV bias for repeatability were 8 +/- 92 and 23 +/- 165 ml, respectively, for EELV(Win) and EELV(Wout). During ASB bias for repeatability were 32 +/- 160 and -15 +/- 147 ml, respectively, for EELV(Win) and EELV(Wout). CONCLUSIONS: The LUFU method showed good agreement with helium, and good repeatability during partial and controlled mechanical ventilation. The technique is simple and safe.

Adrenocortical carcinoma -- improving patient care by establishing new structures.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and highly malignant tumour with a poor prognosis. Patients present with signs of steroid hormone excess (e.g., Cushing's syndrome) or symptoms due to an abdominal mass. DIAGNOSIS: In case of an adrenal mass, hormonal workup before surgery is required for differential diagnosis, perioperative management, and for follow-up. The imaging of choice is CT or MRI with MRI being of additional use when invasion of big vessels is suspected. Apart from that, the use of 18-FDG-PET is becoming increasingly established. TREATMENT: Surgical resection is the therapeutic option of choice in stages 1 - 3. In stage 4, the adrenolytic compound mitotane is part of the first-line treatment, but often needs to be combined with cytotoxic chemotherapy. Most patients will eventually have a recurrence, so adjuvant treatment (mitotane/tumour bed radiation) has to be considered in high risk patients, even if randomized controlled trials on adjuvant treatment are still lacking. STRUCTURAL PROGRESS: Several national and European structures have recently been established in order to increase our knowledge of ACC, improve therapeutic options and diagnostic procedures, and promote research. GANIMED, as a Germany-wide network of experts on adrenal diseases, has been founded allowing for improved gathering of data and joint studies. ENSAT (European Network for the Study of Adrenal Tumours) has been brought to life, aiming at European standards for therapy, diagnosis and tumour banking. Since 2003, patients can be enrolled in the German ACC Registry. France and Italy have also developed a central registry to collect nationwide data from patients with ACC. For the first time, patients with metastatic/unresectable ACC can participate in a prospective controlled randomized trial comparing two different cytotoxic chemotherapy regimes (FIRM-ACT).

Estimation of pulmonary blood flow from sinusoidal gas exchange during anaesthesia: a theoretical study.

We simulated the use of simultaneous sinusoidal changes of inspired O2 and N2O (Williams et al., J Appl Physiol, 1994; 76: 2130-9) at fractional concentrations up to 0.3 and 0.7, respectively, to estimate FRC and pulmonary blood flow (PBF) during anaesthesia, using O2 as an insoluble indicator. Hahn's approximate equations, which neglect the effect of pulmonary uptake and excretion on expiratory flow, estimate dead space and alveolar volume (VA) with systematic errors less than 10%, but yield systematic errors in PBF which are approximately proportional to FIN2O in magnitude. A correction factor (1 - P)-1 for Hahn's equations for PBF (where P is the mean partial pressure of the soluble indicator) reduces the dependence of PBF estimates of FIN2O, and the solution of equations describing the simultaneous mass balance of both indicators yields accurate results for a wide range of mean FIN2O. However, PBF estimates are sensitive to measurement errors and a third gas must be present to ensure that the indicator gases behave independently.

Time course evolution of ventilatory responses to inspiratory unloading in patients.

Inspiratory muscle unloading decreases ventilatory drive. In this study, we examined the time course of this effect in patients with chronic obstructive pulmonary disease receiving two modes of ventilatory support: pressure support ventilation (PSV), during which each cycle was assisted, and biphasic positive airway pressure (BIPAP), set up in such a manner that one spontaneous breath took place between two consecutive pressure-assisted breaths. The first breath following the switch from spontaneous breathing to PSV was associated with an increase in tidal volume (VT) and a drop in mean transdiaphragmatic pressure (mean Pdi) and inspiratory work (WI) performed per liter but with unchanged values of esophageal occlusion pressure at 100 ms (Pes 0.1), diaphragmatic electrical activity (EMGdi), and WI performed by breath. The same phenomena were observed for the assisted breath of BIPAP as compared with the preceding spontaneous breath. During the subsequent breaths of PSV, Pes 0.1, EMGdi, and WI performed per breath decreased progressively up to the sixth to eighth breaths, and VT returned to pre-PSV values. We conclude that in patients with chronic obstructive pulmonary disease the decrease in ventilatory drive associated with PSV takes place from the first breath onwards but requires six to eight breaths to be fully achieved. During BIPAP, as a consequence of the kinetics of the PSV-induced downregulation of ventilatory drive, assisted breaths following spontaneous breaths are characterized by an enhanced inspiratory efficiency.

Elevated environmental lead levels in a day care setting.

OBJECTIVE: To determine the risk of lead poisoning among children enrolled in day care centers with elevated environmental lead burdens. DESIGN: Survey. SETTING: Six day care centers on properties owned by a major state-supported university. PATIENTS AND OTHER PARTICIPANTS: One hundred fifty-five of 234 eligible children (mean age, 4.8 years) enrolled in these centers were screened by questionnaire for risk factors of lead exposures. Blood samples for lead levels were also obtained. Observations of day care activities relative to lead exposure risks were recorded. Analyses of lead levels in paint, dust, and/or soil samples at the six centers were obtained. MAIN OUTCOME MEASURES: Prevalence of elevated blood lead levels and associated behavioral risk factors for lead exposure in children attending day care centers. RESULTS: Elevated levels of lead in paint (2.4% to 40% lead) were present in all day care facilities. Three day care centers had elevated lead levels in windowsill dust (62,000 to 180,000 micrograms [corrected] of lead per square meter) or soil (530 to 1100 mg of lead per kilogram): Questionnaires documented low risk for lead exposure to children in the home environments. Direct observations in the day care setting revealed optimal supervision and hygiene of the children. Blood lead levels were less than 0.5 mumol/L (10 micrograms/dL) in all but one of the 155 children screened. CONCLUSIONS: Children attending day care centers with high environmental lead burdens need further documentation of blood lead levels, at-risk behaviors, and lead exposure risks in the home environments as an adjunct to the instigation of lead abatement procedures at the day care centers.

Immune thrombocytopenia and elemental mercury poisoning.

Three cases of severe mercury toxicity occurring within a family are reported. Two cases of thrombocytopenia occurred in this family and represent the second such report in the literature of an association between elemental mercury toxicity and thrombocytopenia. Three of the children presented with a combination of dermatologic and neurologic manifestations reminiscent of acrodynia or pink disease. Each of the four children in this family were treated with dimercaptosuccinic acid. The hazard of vacuuming spilled mercury and appropriate clean-up procedures are described.

Cutaneous vasculitis in the newborn of a mother with cutaneous polyarteritis nodosa.

Vasculitis in an infant of a woman who had a long history of cutaneous polyarteritis nodosa is reported. During the neonatal period the child developed cutaneous vasculitis manifested by livedo reticularis, cutaneous nodules, and acral necrosis. The infant's vasculitis remitted by age 7 months. This is the third such report and strongly suggests the presence of a circulating factor that is capable of crossing the placenta and inducing cutaneous polyarteritis nodosa.

Lead intoxication in Iowa children.

In Iowa, there are over 600,000 residential units built before 1950 which are high risk environments for children due to deteriorating lead paint. However, there are relatively few lead screening programs in Iowa, and only selected children in Iowa have been screened.

Fluid requirements in the preterm infant.

Fluid requirements in the newborn are related to net fluid expenditures, normal changes in body water composition, and the integrity of renal regulatory functions. A variety of clinical conditions and therapeutic modalities also have an important effect on fluid requirements. Fluid therapy must be individualized to meet the specific needs of the infant. Appropriate fluid therapy will facilitate physiologic changes of body water composition and decrease neonatal morbidity.

Renal hemodynamic responses to hypoxemia during development: relationships to circulating vasoactive substances.

Chronically catheterized fetal lambs (n = 11, gestational age 111-139 days) and neonatal lambs (n = 20, postnatal age 4-30 days) were studied to explore during development the relationship of renal hemodynamic responses during hypoxemia to plasma epinephrine concentration (E), plasma norepinephrine concentration (NE), plasma arginine vasopressin concentration (AVP), and plasma renin activity (PRA). A low oxygen gas mixture (11.1 +/- 0.1% O2) was administered for 30 min to the pregnant ewe or neonatal lamb to induce hypoxemia with maintenance of normal arterial pCO2 and pH. Arterial blood pressure was recorded continuously and renal blood flow (RBF) was determined by the radiolabeled microsphere technique. Moderate hypoxemia (pO2 16 +/- 2 torr and 33 +/- 6 torr in fetus and neonate, respectively) induced increases in E, NE (measured by radioenzymatic assay), and AVP (measured by radioimmunoassay) in both fetus and neonate. PRA (measured by radioimmunoassay) also increased in response to hypoxemia in neonatal lambs. The change in mean arterial pressure with hypoxemia (delta MAP) was significant in fetuses (delta MAP 8 +/- 14%, p less than 0.05) but not in lambs (delta MAP 1 +/- 10%, p greater than 0.5). Similarly, the change in renal blood flow with hypoxemia (delta RBF) was significant (delta RBF -51 +/- 24%, p less than 0.001) in fetuses but not in neonatal lambs (delta RBF -9 +/- 38%, p greater than 0.1). These results reflected a change in renal vascular resistance with hypoxemia (delta RVR) that was significant in fetal lambs (delta RVR 169 +/- 168%, p less than 0.01) but not in neonatal lambs (delta RVR 51 +/- 180%, p greater than 0.2).(ABSTRACT TRUNCATED AT 250 WORDS)