Collection of blood mononuclear cells by leukapheresis for transplantation in a yucatan miniature swine model

A large animal model is needed to evaluate new apheresis technologies. These technologies include novel methods of harvesting the blood mononuclear cell population which contains the hematopoietic stem cells needed to restore hematopoiesis in recipients of hematopoietically lethal therapy and the use of cytokines to provide a safe and predictable method of manipulating these circulating hematopoietic stem cells. We describe the methods used to collect mononuclear cells by leukapheresis from Yucatan miniature swine. These animals are of sufficient size to tolerate the procedures and have many physiologic and hematologic similarities to man. They are of good temperament and are easily trained. Long-term venous access was obtained using single lumen silicone rubber catheters placed in the inferior vena cava. The animals were apheresed while fully awake using a Haemonetics Model V50 machine and a modified lymphocyte collection protocol. The procedure was highly efficient for the collection of mononuclear cells and a 10 pass procedure yielded a product which contained 19.7 × 10⁹ mononuclear cells, 10.7 × 10⁹ granulocytes, and 17 ml of erythrocytes in a volume of approximately 100 ml. This product can be cryopreserved and used for subsequent transplantation. The content of four apheresis procedures provides hematopoietic reconstitution of lethally irradiated swine on a time scale equivalent to transplantation of optimal numbers of bone marrow cells. © 1992 Wiley-Liss, Inc.     

A multicenter clinical trial of gadolite oral suspension as a contrast agent for MRI

The purpose of this study was to assess the effectiveness and safety of Gadolite Oral Suspension as a gastrointestinal (GI) contrast agent for MRI in a phase II and two phase III multicenter clinical trials. Gadolite was administered to 306 patients with known or suspected abdominal and/or pelvic disease. MRI with T1- and T2-weighted sequences was performed before and after ingestion. Efficacy was evaluated by having two masked readers rate the certainty of their MR diagnosis (0 = uncertain, 1 = probable, 2 = definite) on randomly presented pre- and post-Gadolite Oral Suspension enhanced images. Principal investigators also evaluated the images and established the final diagnosis. Vital signs, clinical chemistries, and adverse events were documented. Blood and urine samples were analyzed for gadolinium content to determine whether Gadolite Oral Suspension was absorbed systemically. Certainty in MR diagnosis increased significantly (P < .001) for both blinded readers between pre- and post-Gadolite images (.49–1.18 for reader 1; .46–1.53 for reader 2). Sensitivity, specificity, and accuracy also increased for both masked readers. No gadolinium was detected in blood or urine samples. There were no serious adverse events and no apparent drug-related trends in mean vital signs or laboratory values. Gadolite is a highly effective, safe, and well tolerated contrast agent for clinical use with MRI.     

The effect of mode of delivery on neonatal mortality in very low birthweight infants born in Victoria, Australia: Caesarean section is associated with increased survival in breech-presenting, but not vertex-presenting, infants

To determine whether the improved survival of very low birthweight (VLBW) infants (< 1500 g) born in Australia can be attributed to currently high rates of Caesarean section, we examined the associations between neonatal mortality and Caesarean section in singleton liveborn VLBW infants (500–1499 g) born during 1986–93 in Victoria, Australia, using data from the Victorian Perinatal Collection Unit. The infants included in this study had completed > 23 weeks of gestation, had no life-threatening malformations and had not been delivered by a repeat Caesarean without a trial of labour (n = 2763). For infants weighing 500–749 g, 750–999 g, 1000–1249 g and 1250–1499 g, the neonatal mortality rates were 56.1%, 25.7%, 13.0% and 4.3% respectively, and the Caesarean section rates were 33.1%, 42.3%, 54.8% and 55.8%. Nearly half of these births (n = 1269) were associated with one or more obstetric indications for Caesarean section (non-breech malpresentaion, fetal distress, prolapsed cord, placenta praevia, pre-eclampsia and hypertension). Overall, the odds ratio (OR) for neonatal death associated with Caesarean section was 0.92 [95% confidence interval 0.60–1.41], after adjustment for gestational age, birthweight, year of birth, type of hospital, presence or absence of labour, presentation and obstetric indications for Caesarean section. However, when the vertex-presenting (n = 1702) and breech-presenting (n = 746) infants were considered separately, the adjusted ORs for neonatal death were 1.98 [0.96–4.10] and 0.52 [0.29–0.96] respectively. For those infants without obstetric indications for Caesarean section, the adjusted ORs for neonatal death in vertex-presenting (n = 950) and breech-presenting (n = 446) infants were 3.80 [1.11–13.0] and 0.47 [0.23–0.6]. These recent population - based data support the view that Caesarean section does not enhance the neonatal survival of VLBW babies when obstetric complications are absent.     

Neointimal hyperplasia in balloon-injured rat carotid arteries: the influence of hyperhomocysteinemia.

PURPOSE: Hyperhomocyst(e)inemia (hH[e]) is a risk factor for atherosclerosis. Neointimal hyperplasia (NH) after vessel injury can contribute to atherosclerosis. In this study, we investigated the effects of hH(e) on NH formation after arterial balloon injury in rats. METHODS: Lewis rats that were given a hH(e)-inducing (high methionine, low folate) or normal diet for 150 days underwent common carotid artery (CCA) balloon injury. Two and 4 weeks after injury, CCAs were formalin perfusion-fixed, sectioned, and stained for elastin. Neointimal index (NI, percent lumen occlusion) and neointima (N) and media (M) area were measured by using computer-interfaced microscopy. RESULTS: Plasma homocyst(e)ine (H[e]) levels were elevated in rats given the study diet compared with rats given the normal diet at days 40 and 90 (69 +/- 8 and 73 +/- 9 micromol/L vs 4 +/- 0.4 and 4 +/- 0.6 micromol/L, P <.001). After balloon injury, the CCA NI and N/M ratio, but not the M area, were increased by hH(e) compared with normal plasma H(e) (2 weeks [n = 6,7]: NI = 7.3 +/- 1.7 vs 2.9 +/- 0.7, P =.002, and N/M = 0.31 +/- 0.08 vs 0.08 +/- 0.02, P <.001; 4 weeks [n = 4,7]: NI = 13.1 +/- 2.2 vs 6.3 +/- 1.3, P =.002, and N/M = 0.36 +/- 0.08 vs 0.17 +/- 0.03, P <.001). CONCLUSION: hH(e) accelerates NH in a rat CCA balloon-injury model. The effect of hH(e) on NH may contribute to increased atherosclerosis in humans with hH(e).     

Implosive therapy for the treatment of combat-related PTSD

Implosive therapy for the treatment of post-traumatic stress disorder is based on the principle of exposing the patient to trauma-related cues until there is a reduction in the anxiety associated with the cues. It is a relatively specialized procedure regarding which few clinicians receive extensive supervised training, despite the numerous case studies that demonstrate its effectiveness. The present paper addresses a number of procedural issues and offers guidelines for conducting implosive therapy with traumatized combat veterans. Elements of controversy regarding the application of implosive therapy are discussed.