Differences in onset of disease and severity of psychopathology between toxoplasmosis-related and toxoplasmosis-unrelated schizophrenia.

OBJECTIVE: Toxoplasmosis is a lifelong parasitic disease that appears to be associated to schizophrenia. However, no distinguishing attributes in Toxoplasma-infected schizophrenia patients have been described as yet. METHOD: We searched for differences in symptom profile, cognitive performance and treatment response between 194 Toxoplasma-free and 57 (22.7%) Toxoplasma-infected schizophrenia patients treated in Prague Psychiatric Centre between 2000 and 2010. RESULTS: Infected and non-infected patients differed in severity of symptoms (P = 0.032) measured with the Positive and Negative Symptom Scale (PANSS). Infected patients scored higher in positive subscale of PANSS, but not in the general and negative subscales. Infected men scored higher also in Total PANSS score, and negative, reality distortion, disorganisation and cognitive scores. Higher PANSS scores of positive, negative and disorganised psychopathology were associated with the lower titres of anti-Toxoplasma antibodies suggesting that psychopathology deteriorates with duration of parasitic infection. Infected patients remained about 33 days longer in hospital during their last admission than uninfected ones (P = 0.003). Schizophrenia started approximately 1 year earlier in infected men and about 3 years later in infected women, no such difference was observed in uninfected subjects. CONCLUSION: Latent toxoplasmosis in schizophrenia may lead to more severe positive psychopathology and perhaps less favourable course of schizophrenia.

Synthesis and characterization of the colistin peptide polymyxin E1 and related antimicrobial peptides.

Two strategies were developed to synthesize the acylated cyclic peptides know as polymyxins. Synthesis of polymyxin E1 and several analogs enabled us to evaluate the minimum inhibitory concentration of individual compounds against Gram-negative bacteria. In this study we also report the first identification of two component peptides in the complex polymyxin fermentation product colistin, a Thr2Ser isoform and an acyl group isomer. Both of these peptides, as well as a known component peptide, Leu7Ile, were similar to polymyxin E1 in potency, suggesting that conservative mutations in the colistin family are functionally inconsequential. In contrast, the acyclic analogs of all of these peptides were inactive, indicating that the characteristic lariat structure of the polymyxins is necessary for antimicrobial activity.

Lymphocytic hypophysitis. Report of 3 new cases and review of the literature.

Lymphocytic hypophysitis is an uncommon but increasingly recognized disorder characterized by chronic inflammation and destruction of the anterior pituitary. Three new cases are presented here with a review of the 27 previously reported cases. The disease affects primarily young women in late pregnancy or in the postpartum period but also has been described in postmenopausal women and in one man. It presents as an expanding intrasellar mass or as partial or panhypopituitarism. The etiology may be autoimmune. The natural history of this entity begins with enlargement of the pituitary secondary to inflammatory infiltration and progresses to atrophy of the gland with destruction of pituitary tissue and replacement with fibrosis. At least 1 patient had documented recovery of pituitary function, and the overall potential incidence of recoverable function is unknown. Our improved understanding of this disease has led us to conclude that surgical intervention is not always necessary.

Addisonian crisis while taking high-dose glucocorticoids. An unusual presentation of primary adrenal failure in two patients with underlying inflammatory diseases.

The diagnosis of acute hypoadrenalism seldom is considered in patients without known adrenal insufficiency who are taking supraphysiologic amounts of glucocorticoids. We report two patients who presented in acute addisonian crisis on more than one occasion while taking high doses of glucocorticoids (30 to 40 mg of prednisone daily) for underlying inflammatory disease (recurrent pleuropericarditis and sarcoidosis). Evidence of severe mineralocorticoid deficiency was present in each patient, and the conditions of both improved remarkably when mineralocorticoid was added to their regimens. The cause of primary adrenal failure and its acute presentation was unclear in both patients but is presumed to be related to the underlying inflammatory disease.

Bilateral luteomas of pregnancy in a patient with diabetes.

A patient with diabetes and luteomas of the ovaries demonstrated a significant and progressive rise in the serum levels of androstenedione and testosterone during pregnancy. The levels of these hormones were also elevated in cord blood and ovarian fluid. The increased insulin requirement to maintain euglycemia was observed at an earlier date in this pregnancy than in her previous pregnancy.

Measurements of respiratory ammonia and the chemical neutralization of inhaled sulfuric acid aerosol in anesthetized dogs.

The extent of neutralization of inhaled H2SO4 aerosol by endogenous NH3 has been measured in the surgically isolated upper airways of anesthetized dogs. Neutralization was observed to be inversely proportional to particle size. The H2SO4 particles with initial dry diameters of 0.5 micrometer and 1.0 micrometer underwent 0.28 (+/- 0.08) and 0.06 (+/- 0.06)% neutralization per ppb of laryngeal NH3, respectively, during passage through the mouth and out of the larynx at a flow of 0.1 L/s. At either particle size, neutralization is related to the route of entry, being greater for entry via the mouth than the nose. Limited measurements for entry via the mouth show more neutralization of 0.7 micrometer particles at 0.1 L/s than at 0.2 L/s. These results are consistent with a reaction that is limited by the rate of NH4 diffusion to the particle's surface.

Quantitative indices of intra-aortic balloon pump (IABP) dependence during post-infarction cardiogenic shock.

This study attempts to quantitate post-infarction cardiogenic shock IABP dependence in instances of massive myocardial infarction with the use of hemodynamic indices plotted over time-course trajectories. Mortality is predicted when age and hemodynamic performance are also considered. It appears that post-infarction IABP dependence can be quantitated and that such information can be useful in considering diagnostic and therapeutic alternatives during the course of IABP support and cardiogenic shock. The analysis suggests that such IABP-dependent patients could be considered for therapeutic alternatives. They do not expire during the first 50 hours of IABP support and neither improve nor deteriorate during the second 50 hours of support. They remain in Class B without the occurrence of life-threatening ventricular dysrhythmias for a sufficient time for cardiac catheterization to determine the appropriateness of corrective procedures.

The chemical neutralization of inhaled sulfuric acid aerosol.

We hypothesize that gaseous ammonia (NH3) released into respiratory airways can neutralize inhaled acidic particles and alter or mitigate their toxicity. To test this hypothesis, we have examined the relationship between respiratory NH3 and the chemical neutralization of inhaled sulfuric acid (H2SO4) aerosol in the surgically isolated upper airways of anesthetized dogs. With air entering via the mouth, the NH3 concentration measured at the larynx, ranged between 30 and 225 parts per billion (ppb). The extent of neutralization at this point ranged from 8%-70% (n = 16) for the 0.5-micrometer particles and 7%-22% (n = 16) for the 1.0-micrometer particles. With air entering via the nose, the laryngeal NH3 concentrations ranged between 50 and 220 ppb. Neutralization values were between 15%-65% (n = 8) for 0.5-micrometer particles, and between 16%-18% (n = 3) for 1.0-micrometers particles. For both routes of entry, the extent of neutralization was correlated with the laryngeal NH3 concentration. We conclude that the chemistry of acidic particles is significantly altered by respiratory NH3 during inhalation. The extent of neutralization is related to both the NH3 concentration in the airway and the size of the particle entering the airway. The extent of neutralization per ppb of laryngeal NH3 is related to the route of entry, being greater for the mouth than the nose.

RIGHT AND LEFT VENTRICULAR HEMODYNAMIC INDICES AS PREDICTORS OF THE NEED FOR AND OUTCOME OF POST-CARDIOTOMY MECHANICAL INTRAAORTIC BALLOON PUMP SUPPORT.

Preoperative cardiac catheterization data of 21 patients requiring intraaortic balloon pumping (IABP) for weaning from cardiopulmonary bypass were analyzed and compared with similar data in 28 patients who underwent nearly similar operative procedures, but did not require IABP for weaning. Cardiac index (CI) and systemic vascular resistance (SVR) were found to have predictive value for the need of IABP for weaning from cardiopulmonary bypass and differentiated survival from non-survival. Left ventricular end diastolic pressure (LVEDP) was not found to be predictive. Ejection fraction (EF) was significantly lower in those who required IABP than those who did not; EF did not predict the outcome. Pulmonary capillary wedge pressure ([unk]), pulmonary artery pressure ([unk]) and pulmonary vascular resistance (PVR) were predictive of the need for IABP, but not the outcome. Left ventricular minute work index (LVMWI) was significantly lower in those requiring IABP, right ventricular minute work index (RVMWI) was predictive of survival with IABP. Together, LVMWI and RVMWI were predictive of the need for and outcome of IABP following cardiopulmonary bypass. Twenty-seven of 28 control RVMWI's were normal. No patient requiring IABP had depressed RVMWI's preoperatively. Elevated preoperative RVMWI's were associated with 80% survival with postcardiotomy IABP; normal RVMWI's were associated with a 56% survival with post-cardiotomy IABP. Elevated preoperative RVMWI's reflected moderate to maximal right ventricular compensatory capacity in response to depressed left ventricular function. Normal preoperative RVMWI's in the presence of depressed LVMWI's were indicative of decreased right ventricular compensatory capacity in post-cardiotomy IABP-support settings. Right ventricular function is as important as left ventricular function as a prognosticator for the need and outcome of IABP support of the failing post-cardiotomy circulation.

CLINICAL TRIALS OF THE ABDOMINAL LEFT VENTRICULAR ASSIST DEVICE (ALVAD): PROGRESS REPORT.

An abdominal left ventricular assist device (ALVAD) is undergoing controlled clinical trials in our institution. The ALVAD is pneumatically-actuated, synchronously or asynchronously with an external console and is interposed between the apex of the left ventricle and the infrarenal abdominal aorta. It is an order of magnitude more effective than conventional intraaortic balloon pumping. Thus far, we have implanted this pump in 21 patients (15 males and six females). The average age has been 50. The duration of cardiopulmonary bypass with intensive pharmacologic support and IABP until ALVAD implantation has been nearly 4 hours. The plasma hemoglobins prior to ALVAD implantation have averaged 168 mg%. The platelet counts at implantation have averaged 68,000 mm(3). The average duration of ALVAD support has been in excess of one day and the longest trial extended for one week. We have been able to remove the pump after ventricular recovery in two instances and effected cardiac allografting in one instance of ALVAD dependency. We have found that (1) the profoundly depressed left (and right) ventricles can recover if totally supported with this device; (2) the device can function in the presence of ventricular fibrillation and/or standstill; (3) the device can effectively replace both left and right ventricular function in the presence of normal pulmonary vascular resistance and microcirculatory hemodynamics; and (4) in the presence of impending multiple organ failure, procrastination in use is to be avoided.

ULTRASTRUCTURAL ANALYSES OF STONE HEART SYNDROME AT ONSET AND SIX DAYS LATER FOLLOWING TOTAL SUPPORT OF THE CIRCULATION WITH A PARTIAL ARTIFICIAL HEART OR LEFT VENTRICULAR ASSIST DEVICE (ALVAD).

Ischemic myocardial contracture developed in a 21-year-old man following aortic and mitral valve replacement. The patient's circulation was supported totally for 6 days with an abdominal left ventricular assist device (ALVAD). Cardiac allografting was then undertaken. Samples of myocardium taken at the original operation and 6 days later at transplantation were analyzed ultrastructurally. At the onset of ischemic cortracture, left ventricular abnormalities included hypercontraction of myofibrils, loss of normal A-band and Z-band patterns, mitochondrial swelling with fusion of cristae, interfibrillar edema and glycogen depletion. Capillaries demonstrated swelling of endothelial cells and basement membrane disruption. Six days later, ultrastructural morphology showed further degeneration. The myofibrils remained hypercontracted, but were more fragmented. Degenerative changes in mitochondria were more advanced and calcium deposition in cristae was present. No glycogen was seen. The right ventricular myocardium exhibited significantly fewer ultrastructural abnormalities. The principal right ventricular changes were endothelial swelling and basement membrane disruption. Glycogen granules were present. Ischemic contracture affects the left ventricle more than the right, and the morphology becomes more abnormal with time. To our knowledge, this is the first instance wherein morphologic progressions of the ultrastructural alterations of ischemic contracture have been documented.

A system for rapid measurement of lung function in small animals.

A semiautomated system has been developed to facilitate the rapid measurement of a variety of pulmonary functional parameters in small animals. They include lung volumes, mechanics, flow-volume curves, nitrogen washout curves, and diffusing capacity. The animals are anesthetized, intubated, and ventilated mechanically. The construction of the system is described in detail and the results obtained on rats are compared with those published by other investigators.

Intra-aortic balloon pumping: theory and practice. Experience with 325 patients.

Intra-aortic balloon pumping to support the failing circulation is now an accepted therapeutic modality. The device is simple. Insertion can be accomplished rapidly and efficiently in emergency rooms, coronary care units, cardiac catheterization suites and operating rooms, preoperatively, intraoperatively and postoperatively. The hemodynamic effects are immediate and predictable, and the accruing clinical results show increasing survival and hospital discharge rates. In these institutions, mechanical support of the circulation by this and more advanced methods has been formalized within the responsibility of a Circulatory Support Service. The purpose of this report is to summarize some observations and analyses which have been made during care of 325 consecutive postcardiotomy and/or postinfarction cardiogenic shock patients. Historical, theoretical, basic, and applied aspects and current results are included. Foremost are the straightforward concepts of considering the heart as a pump, the failing heart as a failing pump and intra-aortic balloon pumping as a temporary intravascular, auxiliary pump, capable of stabilizing or reversing that failure if utilized early in its evolution.

Molecular, microscopic, microstructural and mechanical methods of analyzing pseudoneointimal linings within partial artificial hearts in man and the calf.

Ex vivo molecular, microscopic (cellular), microstructural and mechanical methods have been utilized to evaluate biologic, blood-interfacing linings (pseudoneointimal) formed on textured, fibril-flocked pumping surfaces within abdominal left ventricular assist devices (ALVADs) on partial artificial hearts. Thus far, seventeen human and twenty bovine pseudoneointimal linings (1--28 day pumping durations) have been evaluated by these methods. The results indicate that pseudoneointima begins developing within 24 hours after contact of the pumping surface with blood and is well developed at five days. The linings exhibit surface immunofluorescent fibrinogen activity, viable surface macrophages and histiocytes and scattered erythrocytes at ALVAD removal. Structurally similar linings (20 micrometer to 500 micrometer in thickness) develop in calves and in man. Mechanically, pseudoneointima is a stable, adherent, highly compliant, isotropic structural material. It is linearly elastic and strain-rate independent, with small viscous energy losses under physiologic strains. The methods employed for the evaluation of pseudoneointima provide useful information to determine the suitability of textured or rough surfaces for blood interfacing. The cumulative results indicate that the textured surface approach is useful for intermediate-term clinical ALVAD utilization.