[Characteristics of the fetal and infant respiratory system : What the pediatric anesthetist should know]. / Besonderheiten des fetalen und kindlichen Atmungssystems : Was der/die (Kinder­)Anästhesist*in wissen sollte.

Respiratory complications are the most frequent incidents in pediatric anesthesia after cardiac events. The pediatric respiratory physiology and airway anatomy are responsible for the particular respiratory vulnerability in this stage of life. This article explains the aspects of pulmonary embryogenesis relevant for anesthesia and their impact on the respiration of preterm infants and neonates. The respiratory distress syndrome and bronchopulmonary dysplasia are highlighted as well as the predisposition to apnea of preterm infants and neonates. Due to the anatomical characteristics, the low size ratios and the significantly shorter apnea tolerance, airway management in children frequently represents a challenge. This article gives useful assistance and provides an overview of formulas for calculating the appropriate tube size and depth of insertion. Finally, the pathophysiology and adequate treatment of laryngospasm are explained.

[Fetal and pediatric cardiovascular physiology : Things you should know as an (pediatric) anesthesiologist]. / Fetale und kindliche Herz-Kreislauf-Physiologie : Was der/die (Kinder­)Anästhesist*in wissen sollte.

Immediately after birth the physiology of the cardiovascular system of the neonate undergoes some significant changes. The first breaths in life and the inflation of the lungs lead to a considerable drop in pulmonary arterial resistance. This results in the closure of the foramen ovale and ductus arteriosus; however, during the first weeks of life a sharp rise in pulmonary vascular resistance caused by hypoxia, hypercapnia and excessive positive pressure ventilation can lead to the reopening of the ductus arteriosus. This may result in subsequent strain of the left heart. In order to anticipate the reopening of the ductus arteriosus, it is recommended to measure the saturation of peripheral oxygen not only preductal (right hand), but also postductal (feet).An excessive volume therapy should be avoided as the neonatal myocardium is hallmarked by low cardiac compliance, reduced contractility and reduced ventricular filling.Until now there is still no uniform definition of hypotension in pediatric patients. Blood pressure values that are measured in awake children or are derived from the 50% age percentile values can thus only be used as approximate values. In all cases it is mandatory to recognize and consistently treat hypotension during pediatric anesthesia in order to prevent postoperative organ damage, particularly of the brain.The transcranial measurement of cerebral regional oxygen saturation (c­rSO2) by means of near-infrared spectroscopy (NIRS) provides valuable information about regional tissue oxygenation of the brain. This enables conclusions about the state of the multifactorial cerebral perfusion to be drawn. In this way monitoring of the hypoxia sensitive cerebral tissue can be accomplished and should be used in premature infants and neonates. When measuring a baseline in awake patients, a 20% drop of c­rSO2 from this baseline should be challenged and treated if necessary.

A study of dose-proportionality in the pharmacokinetics of the oral direct renin inhibitor aliskiren in healthy subjects.

OBJECTIVE: To evaluate the dose-proportionality of the pharmacokinetics of aliskiren, the first in a new class of orally active direct renin inhibitors approved for the treatment of hypertension. METHODS: This was an open-label, single-center, single-dose, randomized, 4-period crossover study. Following a 21-day screening period, 32 healthy male or female subjects (ages 18 - 45 years) were randomized to 1 of 4 aliskiren dosing sequence groups (8 subjects per group): 75, 150, 300 and 600 mg. Blood samples were obtained for determination of plasma aliskiren concentrations (HPLC/MS/MS) for 96 h post dose. Log-transformed pharmacokinetic parameters AUC and C(max) were analyzed to determine dose-proportionality using the power model, parameter = A*(Dose)(beta), where A = intercept and beta = dose-proportionality coefficient. The predefined dose-proportionality criteria over the dose range 75 â 600 mg were 90% confidence intervals (CI) for beta contained within the range 0.89 - 1.11. RESULTS: AUC and Cmax values increased with increasing doses of aliskiren. Both AUC and C(max) were associated with high variability (coefficient of variation 55 - 64% for AUC and 59 - 117% for C(max)). The estimated proportionality coefficients (beta) for AUC(0-infiniti), AUC(0-t) and C(max) were 1.18 (90% CI 1.10, 1.25), 1.29 (90% CI 1.22, 1.36) and 1.42 (90% CI 1.31, 1.52), respectively. Dose-proportionality was, therefore, not demonstrated across the entire 8-fold dose range. For the clinical dose range of 150 â 300 mg, increases of 2.3- and 2.6-fold were observed for AUC and C(max), respectively. All doses of aliskiren were well tolerated. CONCLUSIONS: Exposure to aliskiren was greater than proportional over the dose range of 75 - 600 mg. Over the therapeutic dose range of 150 â 300 mg approved for the treatment of hypertension, AUC and Cmax increased by 2.3- and 2.6-fold, respectively. The pharmacokinetics of aliskiren show relatively high intersubject variability.

Breast cancer sagittal/horizontal plane location influences axillary lymph node involvement.

AIM: To assess the influence of tumour location on axillary lymph node involvement (ALNI) and prognosis in breast cancer by evaluating the significance of the sagittal/horizontal alignment. METHODS: We compared 57 patients with superficially located breast carcinomas up to 3.0 cm with patients having lesions in posterior planes of the breast. Both groups were matched according to age, time of diagnosis, tumour size, grade, hormonal receptor status and tumour site within the frontal plane. Histologic evidence of skin involvement, excluding tumours fulfilling the criteria for pT4b, was defined as inclusion criteria and reference plane for superficial tumour location. RESULTS: Tumours situated in the superficial region of the breast, compared to those located in deeper planes, have an increased risk of ALNI (p=0.023), whereas no difference was observed with reference to disease-specific survival (p=0.203). CONCLUSION: This study shows that ALNI is dependent on sagittal/horizontal as well as frontal tumour location. Clinicians should be aware that tumours lying posteriorly may be at increased risk of occult spread outside axillary lymph nodes.

Indications and Route of Hysterectomy for Benign Diseases. Guideline of the DGGG, OEGGG and SGGG (S3 Level, AWMF Registry No. 015/070, April 2015)

Background: Official guideline "indications and methods of hysterectomy" to assign indications for the different methods published and coordinated by the German Society of Gynecology and Obstetrics (DGGG), the Austrian Society of Gynecology and Obstetrics (OEGGG) and the Swiss Society of Gynecology and Obstetrics (SGGG). Besides vaginal and abdominal hysterectomy, three additional techniques have been implemented due to the introduction of laparoscopy. Organ-sparing alternatives were also integrated. Methods: The guideline group consisted of 26 experts from Germany, Austria and Switzerland. Recommendations were developed using a structured consensus process and independent moderation. A systematic literature search and quality appraisal of benefits and harms of the therapeutic alternatives for symptomatic fibroids, dysfunctional bleeding and adenomyosis was done through MEDLINE up to 6/2014 focusing on systematic reviews and meta-analysis. Results: All types of hysterectomy led in studies to high rates of patient satisfaction. If possible, vaginal instead of abdominal hysterectomy should preferably be done. If a vaginal hysterectomy is not feasible, the possibility of a laparoscopic hysterectomy should be considered. An abdominal hysterectomy should only be done with a special indication. Organ-sparing interventions also led to high patient satisfaction rates, but contain the risk of symptom recurrence. Conclusion: As an aim, patients should be enabled to choose that therapeutic intervention for their benign disease of the uterus that convenes best to them and their personal life situation.

Prognostic and predictive significance of ErbB-2 breast tumor levels measured by enzyme immunoassay.

PURPOSE: A retrospective analysis to assess the prognostic and predictive clinical value of breast tumor ErbB-2 receptor expression quantified by enzyme immunoassay (EIA), to compare levels measured by EIA with ErbB-2 status determined by immunohistochemistry (IHC), and to correlate receptor content with levels of phosphorylated (Y1248-P) ErbB-2, a measure of functional tyrosine kinase activity. MATERIALS AND METHODS: EIA quantification of ErbB-2 was performed on membrane extracts from 3,208 well-characterized primary breast cancers. Overall, relapse-free, distant disease-free, and local/regional-free patient survival data were available on 1,123 of these tumors. IHC scoring for ErbB-2 status (HercepTest; DAKO, Glostrup, Denmark) was performed on adjacent sections of 151 cases, and receptor functionality was measured in 230 tumors by an antibody specific for phosphorylated (Y1248-P) ErbB-2. RESULTS: Unlike nonmalignant breast tissues, breast tumors showed increased ErbB-2 levels in a bimodal distribution, with 12% constituting a distinct set of ErbB-2-overexpressing tumors. The intermodal threshold value for ErbB-2 overexpression distinguished tumors with reduced estrogen and progesterone receptor content, high IHC score for ErbB-2, and significantly increased levels of phosphorylated (Y1248-P) ErbB-2 receptor. By multivariate analysis, EIA-determined ErbB-2 overexpression predicted significantly reduced patient survival that was unaffected by tamoxifen or cyclophosphamide, methotrexate, and fluorouracil adjuvant therapy. CONCLUSION: Determination of ErbB-2 receptor expression by EIA offers a clinically valuable alternative to semiquantitative IHC assessment of breast tumor ErbB-2 overexpression and affords the opportunity to evaluate ErbB-2 phosphorylation, which may represent an important predictive parameter of receptor functionality.

Blood transfusion-modulated tumor recurrence: first results of a randomized study of autologous versus allogeneic blood transfusion in colorectal cancer surgery.

PURPOSE: Allogeneic blood transfusions have reportedly been associated with a poor prognosis in patients with curatively resected cancer. To control for immunosuppression induced by a speculatively causal allogeneic blood transfusion, we designed a randomized study in which the control group received autologous blood transfusions not related to any condition of immunosuppression. PATIENTS AND METHODS: One hundred twenty patients with potentially curative resectable colorectal cancer and the capability to predeposit autologous blood were randomly selected to receive either standard allogeneic blood transfusion or predeposited autologous blood. RESULTS: In curatively resected cancer patients, the number who needed allogeneic blood transfusions was reduced from 60% in the allogeneic blood group to 33% in the autologous blood group (P = .009). After a median follow-up duration of 22 months (range, 8 to 48) tumor recurrence was observed in 28.9% of the allogeneic blood group and 16.7% of the autologous blood group. Life-table analysis established a tendency toward a shorter tumor-free survival for the allogeneic blood group (log-rank P = .11). The problem with this analysis was the strong association of allogeneic blood transfusions with tumor recurrence, which interfered in 33% of patients in the autologous blood group who required additional allogeneic blood transfusions. Multivariate analysis of established risk factors for tumor recurrence and surgery-related variables reflecting potential immunosuppressive conditions showed that only pT stage (relative risk, 6.61; 95% confidence interval [CI], 1.82 to 23.99; P = .004), pN stage (relative risk, 8.39; 95% CI, 3.15 to 22.33; P < .001), and the need for allogeneic blood (relative risk, 6.18; 95% CI, 2.20 to 17.37; P < .001) were independent predictors of tumor recurrence. Subgroup analysis of patients who received a transfusion of < or = 2 U blood found a significantly higher risk of tumor recurrence in the allogeneic blood group (relative risk, 5.16; 95% CI, 1.13 to 23.62; P = .034), which was reduced to borderline significance (relative risk, 3.54; 95% CI, 0.76 to 16.51; P = .107) by adjustment for tumor (T) and node (N) stage. CONCLUSION: As indicated by these first results, the blood transfusion modality has a significant effect on tumor recurrence after surgical treatment of colorectal cancer. A change in the practice of blood transfusion might thus potentially surpass the impact of any recent adjuvant treatment strategies.

Cardioprotection by aldosterone receptor antagonism in heart failure. Part I. The role of aldosterone in heart failure.

In recent years understanding of the role of aldosterone has expanded beyond the known classic effects of promoting renal sodium retention and potassium and magnesium loss. It is now well documented that aldosterone causes myocardial and perivascular fibrosis, blocks the myocardial uptake of norepinephrine, and increases plasminogen activator inhibitor levels. In conjunction with angiotensin II, aldosterone causes vascular damage, endothelial dysfunction, and decreased vascular compliance. Therefore, the renin-angiotensin-aldosterone system (RAAS) plays a major role in the development of both hypertension and heart failure and is therefore, a key target for therapeutic interventions. Commonly prescribed medications for control of hypertension and congestive heart failure are inhibitors of the RAAS, including angiotensin converting enzyme inhibitors (ACE-I) and Angiotensin II (A-II) receptor antagonists. There is a well-documented increase in aldosterone levels that occurs over several months during chronic treatment with an ACE-I or A-II receptor antagonist. Such suppression of circulating aldosterone however, is transient, as exemplified by the term "escape" used to describe the phenomenon. This rebound of aldosterone even occurs when patients receive both an ACE-I and A-II receptor antagonist. In addition, ACE-I and A-II receptor antagonists are less effective in controlling BP in the estimated 60% of hypertensive patients who are salt (volume) sensitive and more prone to hypertension-associated morbidity such as black patients and type 2 diabetics. Thus chronic and complete blockade of aldosterone action requires an aldosterone receptor antagonist. The "Randomized Aldactone Evaluation Study" (RALES) trial results in patients with severe heart failure NYHA class III or IV and a left ventricular ejection fraction of no more than 35 percent showed that administration of a sub-hemodynamic dose of spironolactone (25 mg a day) as an add on therapy to ACE-I plus standard treatment resulted in a significant mortality reduction due both to decreased death from progressive heart failure and sudden cardiac death. These findings support the pivotal role of aldosterone in the pathophysiology of progressive heart failure. Although it is an effective antialdosterone agent, widespread use of spironolactone in humans is limited by its tendency to produce undesirable sexual side effects. At standard doses, impotence and gynaecomastia can be induced in men, whereas pre-menopausal women may experience menstrual disturbances. Data on a selective aldosterone receptor antagonist, eplerenone, appear promising for the effective blockade of aldosterone and its harmful effects without the sexual disturbances of spironolactone. Recently Eplerenone was successfully introduced for the treatment of hypertension and heart failure. Growing number of experimental studies are finding a broader role for Aldosterone in driving the pathophysiology of both heart failure and hypertension. When added to conventional therapy aldosterone receptor blockers show benefits which are in addition to those conferred by ACE-I and/or AII receptor blockers.

A double-blind dose response comparison of oral enoximone and placebo for congestive heart failure.

Enoximone (MDL 17,043), a newly synthesized imidazole derivate, has been shown to possess both positive inotropic and vasodilating properties. Sixteen patients with congestive heart failure were allocated to receive either enoximone, 50, 100 or 150 mg, or placebo, each given 3 times daily for 4 weeks, to investigate the dose-related efficacy and tolerability of oral enoximone. Symptom-limited exercise capacity improved in 5 of 10 patients in the enoximone group. The ejection fraction increased from 28% to 36% after 4 weeks, to 36% after 8 weeks and to 35% after 12 weeks in the enoximone group. Exercise duration and ejection fraction did not change in the patients in the placebo group. With enoximone, heart rate, blood pressure, Holter monitoring and laboratory tests showed no significant drug-related changes. The addition of oral enoximone to existing therapy with digitalis and diuretics may improve the clinical condition and left ventricular function in patients with congestive heart failure. Enoximone shows clinical efficacy at dosages of 50 mg and 100 mg 3 times daily. With the higher dosage, unwanted side effects increased but efficacy did not. Enoximone did not increase ventricular ectopy in the doses given.

Long-term treatment with oral enoximone for chronic congestive heart failure: the European experience.

The long-term safety and efficacy of the inotropic/vasodilatory agent enoximone (50 to 100 mg 3 times daily) were evaluated in 30 patients with chronic congestive heart failure (New York Heart Association classes II to IV). Nineteen patients had idiopathic dilated cardiomyopathy and 11 had ischemic heart disease. Patients were receiving maintenance therapy of digitalis and diuretics. Cardiac function was assessed at 12 week intervals (physical examination, exercise testing, chest x ray, echocardiography, radionuclide angiography, 24-hour Holter monitoring and blood chemistry). During a mean follow-up of 40 weeks, 6 patients died, due to noncardiac (n = 1) and sudden death (n = 1) and to cardiac failure (n = 4) within 36 weeks of drug treatment. In the remaining patients New York Heart Association class improved in 18, was stationary in 5 and deteriorated in 1. Exercise capacity increased during the first 26 weeks and was maintained improved thereafter. Clinical improvement appeared not to wane with time. No change in heart rate, blood pressure and cardiothoracic ratio was observed. Echocardiographic left ventricular dimensions did not change significantly; however, the fractional shortening increased from baseline (14%) to 19% after 12 weeks, 17% after 26 weeks and 21% after 52 weeks (p less than 0.05). The preejection period/left ventricular ejection time ratio decreased from 0.74 to 0.35, 0.44 and 0.43 (p less than 0.05), respectively. There was an increase in radionuclide ejection fraction from 23% to 27% (difference not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Certain batches of albumin solutions influence the expression of endothelial cell adhesion molecules.

OBJECTIVE: Increased levels of soluble adhesion molecules, a decreased PO2/FIO2 ratio and a tendency to worsened outcome have been reported following the use of human albumin in critical illness. The reasons are not yet understood. Since albumin solutions have previously been shown to contain proinflammatory mediators, a direct upregulation of adhesion molecules by contaminated batches may explain these findings. To examine this, we studied the effects of different albumin preparations on endothelial cell adhesion molecules in vitro. DESIGN: Experimental study. SETTING: Laboratory for cell biology. METHODS: Human umbilical venous endothelial cell cultures (n = 4) were incubated for 6 h at 5 mg/ml with four different human albumin solutions (HA1-4) from different manufacturers. Medium served as the control. Using flow cytometry, the effects on E-selectin, ICAM-1 and VCAM-1 expression were determined on unstimulated cells and on cells stimulated with tumour necrosis factor alpha at 0.5 ng/ml for 4 h. MEASUREMENTS AND RESULTS: On unstimulated cells, HA1 and HA4, two different batches from the same manufacturer, increased ICAM-1 by 22% and 15%, respectively. After stimulation, both solutions resulted in a 19% increased expression of E-Selectin. In addition, HA4 decreased VCAM-1 on stimulated cells (p < or = 0.05). Two albumin preparations from other manufacturers did not produce significant effects. CONCLUSIONS: Some albumin solutions directly modulate adhesion molecule expression on endothelial cells. This may, at least in part, explain the previous finding of increased soluble adhesion molecules and a decreased PO2/FIO2 ratio in critically ill patients undergoing volume replacement with human albumin.

The new phosphodiesterase inhibitor enoximone in patients following cardiac surgery--pharmacokinetics and influence on parameters of coagulation.

Enoximone is a selective inhibitor of the phosphodiesterase-III enzyme (PDE-III) and possesses positive inotropic and vasodilatory properties. The PDE-inhibitor amrinone has been associated with adverse effects on coagulation by decreasing platelets. To investigate the influence of enoximone on hemostasis, 18 patients undergoing elective aorto-coronary bypass grafting and receiving enoximone were compared to a control group (n = 18). In addition, the plasma levels of enoximone and its major metabolite (enoximone-sulfoxide) were studied following a single injection (0.5 mg/kg) and during a continuous infusion (5 and 10 micrograms/kg.min) before, during and after extracorporeal circulation (ECC). No difference between study and control groups was found for the parameters of coagulation during the investigation period; in particular there were no differences in platelet count and platelet function (thrombelastography). Following the single bolus, peak plasma levels decreased during ECC to ineffective levels. Continuous infusion, however, maintained effective plasma levels of enoximone; sulfoxide levels were twice as high as enoximone concentrations up until the end of the investigation period. It is concluded that enoximone can be judged to be safe in respect to its effects on coagulation even following ECC and at relatively high doses. The use of continuous infusion results in plasma levels which remain at an effective concentration through to the time that the patient is transferred to the intensive care unit.

Lack of effect of enoximone on the pharmacokinetics of digoxin in patients with congestive heart failure.

The aim of this study was to investigate if the concomitant administration of the positive inotropic drug enoximone (100 mg tid) has any effect on the morning through levels of the cardiac glycoside digoxin in 17 patients with congestive heart failure (NYHA II-IV). Plasma concentrations of digoxin were 1.05 +/- 0.37 ng/mL before enoximone, 0.95 +/- 0.31 ng/mL at the end of the enoximone treatment period of 1 week and 0.95 +/- 0.36 ng/mL 1 week after cessation of enoximone treatment. Thus, concomitant administration of enoximone had no effect on plasma concentrations of digoxin while on the other hand the hemodynamics as assessed by NYHA-classification and determination of the heart volume improved significantly.

Efficacy and tolerability of glaucine as an antitussive agent.

One hundred and thirty out-patients, affected by acute and chronic cough caused by upper respiratory tract inflammation, took part in two clinical studies aimed at evaluating the efficacy and tolerability of glaucine , a new antitussive agent. The first study involved 90 patients in a double-blind comparative trial of glaucine and codeine: both treatments were administered as a syrup at a dosage of 30 mg 3-times daily for 7 days. The cough suppressant effect of the two treatments was checked by the physician and the patient using a 4-point scale (from absent to severe), and by the patient using a visual analogue scale. Mean scores of the physician's evaluation decreased from 3.0 to 1.10 after codeine and from 3.0 to 0.47 after glaucine (p less than 0.001 between treatments). Mean values of the patients' visual analogue scales decreased from 83 mm to 17 mm after codeine, and from 85 mm to 7 mm after glaucine (p less than 0.001 between treatments). Constipation and nausea were reported by 9 patients on codeine and by no patient on glaucine (p less than 0.01). One patient on codeine was withdrawn from the study after 3 days because of vomiting, constipation and nausea. The second study was an open trial in 40 patients who received glaucine capsules at a dosage of 30 mg 3-times daily for 28 days. The antitussive effect of the treatment was evaluated on the basis of the same criteria as in the first study. The mean score of the physician's evaluation decreased from 3.0 to 0.15 (p less than 0.001); the mean value of the patients' visual analogue scales decreased from 93 mm to 1 mm (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Transthoracic and transesophageal echocardiography to diagnose ventricular septal rupture: importance of right heart infarction.

BACKGROUND: Rapid and accurate diagnosis of ventricular septal rupture (VSR) remains difficult, and the monitoring of hemodynamic deterioration is a prerequisite for the institution of adequate therapy. The timing of surgical repair is a matter of controversy. METHODS: Transthoracic, transesophageal, color Doppler, and contrast echocardiography were evaluated in 17 patients with VSR in whom the diagnosis was confirmed by catheterization, surgery, or necropsy. RESULTS: Routine transthoracic echocardiography visualized VSR in four out of 17 patients and, with additional views, in 12 out of 17 patients. Color Doppler echocardiography identified the rupture in 15 out of 16, and contrast echocardiography in 11 out of 11 patients. VSR was identified using transesophageal echocardiography in six out of nine patients, and using color Doppler and contrast echocardiography in all patients. Eight out of 10 patients who developed right heart myocardial infarction (RMI) died, whereas all patients without RMI survived (P = 0.0070). Similarly, eight out of 10 patients with shock died, whereas all patients without survived (P = 0.0070). Shock occurred more often in patients with RMI (eight out of 10) than in patients without (two out of six). All patients with both RMI and shock died, whereas those without both conditions survived (P = 0.0002). CONCLUSION: Modern echocardiography is the method of choice in the diagnosis of VSR. Right ventricular function should be evaluated in patients with VSR because patients with RMI are at high risk of hemodynamic deterioration, with poor outcome. RMI, visible as abnormal wall motion, was identified better with transesophageal than with transthoracic echocardiography.

Comparison of dobutamine and enoximone for low output states following cardiac surgery.

Low output syndrome sometimes complicates early postoperative states following cardiac surgery. A comparative study of haemodynamic responses to enoximone and dobutamine was carried out in two groups of 20 patients each, during a 24-hour postoperative observation period. Parameters in addition to routine measurements were determined using a pulmonary artery catheter. Enoximone, 1 mg/kg i.v. in total, was given in the first 20 minutes. The infusion was then reduced to 3-20 micrograms/kg/minute for the next 24 hours. Dobutamine was administered in a continuous dose of 5-7 micrograms/kg/minute over the same period. After 15 minutes' therapy with enoximone, cardiac index increased from 2.31 +/- 0.34 litres/minute/m2 to 3.30 +/- 0.38 litres/minute/m2; after 120 minutes to 3.83 +/- 0.60 litres/minute/m2 and after 24 hours to 4.34 +/- 0.50 litres/minute/m2. Pulmonary capillary wedge pressure at the same intervals decreased from 15.21 +/- 1.65 mm Hg initially to 12.11 +/- 2.83, 11.2 +/- 4.50 and 8.77 +/- 2.98 mm Hg. After dobutamine, cardiac index rose from 2.33 +/- 0.60 litres/minute/m2 to 2.90 +/- 0.81 (15 minutes), 3.52 +/- 0.74 (120 minutes) and 4.12 +/- 1.07 litres/minute/m2 (24 hours). The pulmonary wedge pressure values decreased in this group, from 15.20 +/- 3.14 mm Hg at the beginning to 13.74 +/- 3.02 (15 minutes), 12.17 +/- 5.25 (120 minutes) and 9.81 +/- 4.23 mm Hg (24 hours). The enoximone group showed a diminution of systolic arterial pressure of 14% in the first 120 minutes, with a return to initial values after 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell death in the mosaic epididymis of sex reversed mice, heterozygous for testicular feminization.

Sex reversed mice heterozygous for testicular feminization are genetic females which are converted to males by the autosomal Sxr ("sex reversed") mutation, thus imitating the Y-chromosome. They carry on one of their X-chromosomes the mutation for testicular feminization. Then, X-inactivation leads to the formation of a mosaic of androgen insensitive XTfm and androgen sensitive X+ cells. In the epididymis the Tfm cells are maintained into adulthood as undifferentiated flat cells. There are however, always less Tfm cells than expected from random X-inactivation. Therefore, in the present study the role of cell death in the modification of the original mosaic is investigated before and after castration. It is shown that survival or elimination of Tfm cells depends on the structure of the smooth muscle layers around the epididymal duct. In addition to elimination of whole Tfm sections, a steady loss of single cells, not only in the Tfm but also in the wild-type fraction occurs. In the connective tissue distinct necrotic areas are present. After castration massive necroses appear in both cell types. In Tfm sections disintegration of the wall layers again leads to elimination of Tfm cells and to protrusion of epithelial cells in the interstitium which later on may be organized as abnormal sprouts and ducts. The observations indicate that the testosterone dependent trophic principle is based on short-range intercellular interactions and presumably arises in the connective tissue component of the epididymis.