Thrombotic Micro‐Angiopathy with Sirolimus‐Based Immunosuppression: Potentiation of Calcineurin‐Inhibitor‐Induced Endothelial Damage?

Thrombotic microangiopathy is a rare but important finding in the context of organ transplantation. Acute renal insufficiency in the setting of hemolysis and thrombocytopenia, a triad that constitutes 'hemolytic uremic syndrome', can be associated with, or triggered by, conditions such as verocytotoxin-producing Escherichia coli, viral infections, malignant hypertension, scleroderma, allograft rejection, lupus erythematosus, pregnancy, and medications including mitomycin C, calcineurin inhibitors, and oral contraceptives. After renal transplantation, it can occur, as either a de novo episode, or recurrent disease. Calcineurin inhibitors have long been associated with post-transplantation thrombotic microangiopathy. Sirolimus has been used as a primary immunosuppressant in patients transplanted with a history of earlier hemolytic-uremic syndrome, and also as rescue therapy in patients with calcineurin-inhibitor-associated thrombotic microangiopathy. We describe four cases where there was significant thrombotic microangiopathy in the context of contemporaneous or contiguous calcineurin inhibitor and sirolimus usage. As the intrarenal cyclosporin concentration is thought to be significantly elevated when cyclosporin and sirolimus are used together, this may explain these findings, and mandates caution in their co-administration.     

Cardiac arrest in acute myocardial infarction: its signs, the effect of resuscitation and outcome

A study of 585 patients with acute myocardial infarction (285 with and 300 without cardiac arrest) showed the two groups to differ significantly in terms of clinical, laboratory and electrocardiographic findings. Resuscitation effectiveness depended upon the form of cardiac arrest (chi 2 = 209.25; p less than 0.001). A stable resuscitation effect (survival within and beyond 28 days after the onset of acute myocardial infarction) was achieved in 78.4% of cases of primary ventricular fibrillation, 24.0% of cases of secondary ventricular fibrillation, and 4.9% of asystolia cases. All cases of electromechanical dissociation were fatal. Long-term follow-up showed that 17.3% of patients with cardiac arrest and 21.9% of patients without cardiac arrest died over 4 years (p greater than 0.05).     

Initial findings on preventive intervention for families with parental affective disorders.

OBJECTIVE: The purpose of this study was to develop a clinician-based cognitive, psychoeducational, preventive intervention for families with parental affective disorder that would be suitable to widespread use, test its feasibility and safety, and define the areas affected by the intervention. The intervention was designed to increase understanding of parental illness and resilience in the children. METHOD: The authors studied the first seven families (14 parents) to receive the intervention. Enrollment criteria included affective disorder during the preceding year in at least one parent, presence of at least one child between the ages of 8 and 14 years who was not psychiatrically ill at the time of participation, and willingness to participate in the research study. The intervention consisted of parent, child, and family sessions. Assessment included semistructured interviews with parents about affective disorders, standard ratings of marital satisfaction and therapeutic alliance, and a recently developed semistructured interview to assess response to the intervention. RESULTS: Overall satisfaction with the intervention was rated moderate to high by parents. No harm was reported. Ten of 14 parent subjects reported five or more behavior and attitude changes that they attributed to the intervention. The most frequent behavior and attitudinal changes reported were increased discussion of the illness and related issues and increased understanding of information about affective illness. CONCLUSIONS: The authors conclude that the intervention is safe and feasible in families with parental affective disorder.     

Listeria species in domestic environments.

Using a direct isolation method Listeria spp. were detected in 101 (47.4%) of 213 houses investigated. L. monocytogenes was present in 45 houses (21.1%). Listeria spp. occurred at all sampling sites. Dish-cloths (37%) and surface samples round the drain in the bathroom (27.2%) were most frequently contaminated. Highest numbers (c. 10(4) c.f.u./object) were found in dish-cloths and washing-up brushes. Lower levels (up to 10(3) c.f.u./object) were obtained from kitchen sinks, refrigerator vegetable compartment samples and tooth brushes. In total, 132 isolations of Listeria spp. were made from 871 samples. L. innocua (53%) and L. monocytogenes (41%) were the predominant species in the positive samples. Other Listeria spp. were found in only 6% of the positive samples.     

Scanning laser ophthalmoscopy. Its value in macular diseases

The scanning laser ophthalmoscope provided a high quality television image of the fundus with minimal illumination of the retina. This new device based on a totally new electro-optical principle allowed a detailed exploration of macular function directly under simultaneous fundus control. The focused beam of a yellow krypton laser (568,2 nm) was swept up and down, rights and links across the fundus to form a raster of parallel lines on the retina. The S.L.O. illuminated only a single retinal point at a time and illumination was reduced to less than 70 microw/cm2 versus 100,000 microns/cm2 for indirect ophthalmoscopy and 4,000,000 microw/cm2 for fluorescein angiography. The intensity of the laser beam could be modified with the microcomputer by means of an acousto-optic modulator. It was possible to produce static or dynamic graphic designs that were simultaneously viewed by the patient and observed by the examiner on the patient's fundus on the video monitor. Further computerized analysis of the videotaped scanning laser ophthalmoscopic images gave a functional retinal map with correction for shifts of stimulus position due to fixational saccadic eye movements. The map showed true retinal location of 1. fixation area; 2. scotoma. The clinical evaluation was completed with 3. measurement of visual acuity in any foveal or parafoveal location. The results of scanning laser ophthalmoscopy were illustrated with the report of datas in a patient with diffuse retinal pigment epithelial decompensation.     

Semipermeable Hollow Fiber Membranes in Hepatocyte Bioreactors: A Prerequisite for a Successful Bioartificial Liver?

Abstract: Recent studies have shown that liver support systems based on viable hepatocytes can prolong life in animal models of acute liver failure. Now the time has come to elucidate the design characteristics that are essential to construct an efficient bioreactor. The gold standard remains the intact liver. Despite the very high cell density in this organ, individual cell perfusion is guaranteed resulting in low diffusional gradients which are essential for optimal mass transfer. These conditions are not met in bioreactors based on hollow fiber membranes. Moreover, the semipermeable membranes can foul and act as a diffusional barrier between the hepatocytes and the blood or plasma of the recipient. We devised a novel bioreactor for use as a bioartificial liver that does not include hollow fiber membranes for blood or plasma perfusion. The device is based on an integral oxygenator and a nonwoven polyester matrix material for hepatocyte culture as small aggregates. The efficacy of this original design was tested in rats with liver ischemia. Preliminary results show statistically significantly improved survival; life was prolonged 100% compared to the control experiments.     

Recurrence risk for germinal mosaics revisited.

A formula to calculate recurrence risk for germline mosaicism published by Hartl in 1971 has been updated to include marker information. For practical genetic counselling new, more elaborate tables are given.     

Reproducible model of post-infarction left ventricular dysfunction: haemodynamic characterization by conductance catheter.

OBJECTIVE: The understanding of pathophysiology and cellular mechanisms of chronic heart failure requires the creation of appropriate and accurately characterized animal models, thus enabling meaningful evaluation of evolving medical and surgical therapies. METHODS: The left anterior descending and its diagonal branch were ligated in 12 sheep to induce left ventricular dysfunction. RESULTS: Study of left ventricular pressure-volume loops 3 months post-operatively showed a significant deterioration of both systolic and diastolic indexes of left ventricular function. The left ventricular end-diastolic pressure increased from 3+/-1 to 7+/-1 mmHg (P<0.001) along with a substantial increase in end-diastolic volume from 78+/-8 to 121+/-6 ml (P=0.002) and a significant decrease in cardiac output from 2+/-0.2 to 1.5+/-0.2 l/min (P=0.001). The left ventricular end-systolic pressure-volume relationship deteriorated from 2.7+/-0.37 to 0.7+/-0.16 mmHg/ml (P=0.0002) along with a significant reduction in the pre-load recruitable stroke work (P=0.001). The ejection fraction decreased from 34+/-2% to 16+/-4% (P<0.001) with a significant decrease in +dp/dt and -dp/dt (P=0.009). The mean systemic blood pressure, however, was maintained due to a substantial increase in the systemic vascular resistance (P=0.007). CONCLUSION: This study describes a reproducible large animal model of left ventricular dysfunction. This model is potentially useful to study the pathogenesis of remodelling, surgical management of heart failure and development of novel treatment strategies.