Long-term results of short segmental syngeneic small intestinal transplantation: comparison of jejunal and ileal grafts

A short-segment intestinal graft is favorable to reduce the rate of rejection and the incidence of graft-versus-host disease in recipients of small intestine transplantation. To determine whether a jejunal or an ileal graft is preferable with respect to intestinal morphology and function, syngeneic two-step small intestinal transplantations were performed using male Lewis rats (RT1(1)). They were divided into two groups according to the small intestine donor site (group 1 received 10 cm of jejunum; group 2 received 10 cm of ileum). There was no significant difference in the survival rate or weight gain between the two groups. Nearly all the hematologic findings, serum nutritional parameters, and results of liver function tests were normal for both groups. The only difference was that the serum total bile acid level was significantly higher in group 2. Fifty weeks after transplantation, the graft mucosa showed normal architecture, with adaptive hyperplasia of villi and crypt noted through histological study. The villus height of group 1 was 595 +/- 64 microns (control, 452 +/- 67 microns); that of group 2 was 732 +/- 53 microns (control, 217 +/- 20 microns). The crypt depth of group 1 was 228 +/- 35 microns (control, 165 +/- 24 microns); that of group 2 was 320 +/- 19 microns (control, 102 +/- 19 microns). These compensatory changes were more pronounced in group 2. The authors conclude that, on the basis of long-term functional capacity, there was no significant difference between jejunal and ileal grafts, and that both segments were suitable for transplantation. However, the ileal graft was considered to be better with respect to morphological adaptation.     

Tolerance in liver transplantation: facts and perspectives

Seven patients who had undergone a pneumonectomy for lung cancer developed a second tumor in the remaining lung after a mean time of 28.5 months and underwent a further resection. Preoperative evaluation was based on standard functional tests and on the "stair climbing test". Three patients were operated on using an extracorporeal oxygenator to work on a collapsed lung, three using standard anesthesiologic techniques, and one using high-frequency jet ventilation. There was no operative mortality. Complications occurred in two patients, requiring a temporary tracheostomy in one case. No patient required home oxygen supplementation. Four patients died of metastatic disease after 4, 8, 10, and 12 months, while two patients are alive and free of disease after 83 and 9 months, one is alive and free of symptoms but with a local recurrence after 29 months. Lung resection for bronchogenic carcinoma on a single lung can be safely performed provided that careful clinical judgment is used; long-term survival can be achieved with the resection of the new tumor.     

Kidney transplantation without previous dialysis: limitations, but also possibilities

Kidney transplantation guarantees a better quality of life than dialysis and is less costly. Transplantation without preceding dialysis is an attractive option. However, transplantation long before end-stage renal failure prolongs the period of exposure to immunosuppressive therapy, thereby increasing the risk of malignancy. Transplantation at one year before dialysis-dependency is expected would seem an acceptable compromise. Unfortunately, this option is purely theoretical because there is a long waiting-list due to the existing donor shortage. Patients are usually put on the waiting-list after dialysis has already been started. Extension of the list with pre-dialysis patients is currently only justifiable in exceptional cases. These limitations do not apply to patients who have received an offer of kidney donation from a living (related or unrelated) donor. In these patients transplantation can be done as soon as the creatinine clearance has reached a level of 10-12 ml per minute. More attention should be paid to this form of transplantation, because it can help to decrease the donor shortage.     

Arthroscopy: possibilities and limitations in the diagnosis and therapy of meniscus lesions

The menisci consist of fibrocartilage and are an important supporting structure of the knee joint. They are poorly vascularized and have to withstand a high mechanical strain and load; therefore, lesions are common, especially on the medial side. Meniscal lesions are among the most frequent surgical procedures in orthopedic surgery. Meniscal lesions are diagnosed by a careful clinical examination in 80% of all cases in spite of modern imaging techniques such as magnetic resonance imaging (MRI). In the last 15 years, arthroscopic meniscectomy has become the 'golden standard' of therapy. Arthroscopy provides a powerful tool to precisely locate and classify the type of meniscus injury and to perform arthroscopic meniscectomy at the same time. This means less morbidity, reduced hospitalization time and earlier return to work and hence reduced costs. The endoscopic technique allows to exactly remove the damaged parts of the meniscus with precision instruments (partial meniscectomy). Former open techniques only allowed the complete removal of the meniscus. The arthroscopic techniques used nowadays allow a preservation of the functionally important edge of the meniscus, which is responsible for the stability and the biomechanics of the knee joint and can thus prevent an early onset of arthrosis. In rare cases of peripheral meniscal tears in young patients, arthroscopic refixation is an advantageous treatment option. Partial arthroscopic meniscectomy and arthroscopic meniscus refixation are challenging therapeutic procedures that require a trained and experienced orthopedic surgeon. Today diagnostic arthroscopy is more and more abandoned in favour of noninvasive and reliable MRI techniques. MRI is also useful in cases of previous knee surgery and clinically unclear findings, but should not be used on a routine basis. In differential diagnosis, the orthopedic surgeon always has to evaluate the MRI findings as to their impact. Today, arthroscopic knee surgery is a reliable, technically sophisticated and standardized technique to treat meniscal damages of all patients. There is a relatively low rate of complications, provided that the indication for the procedure is critically applied and restricted to patients with sufficient clinical and MRI findings.     

Virtual cystoscopy based on helical CT scan datasets: perspectives and limitations

The purpose of the study was to simulate cystoscopy based on three-dimensional helical CT scan datasets in real-time in patients with tumours of the urinary bladder. A helical CT scan with double detector technology was carried out pre-operatively in 11 patients with histologically confirmed carcinoma of the urinary bladder and one patient with chronic cystitis. A non-enhanced scan was first performed, followed by an examination in the early phase of contrast medium enhancement. Further images were acquired after adequate filling of the bladder with contrast medium, approximately 30 min after injection. These data were transferred to a separate graphic computer workstation and reconstructed. The results were then compared with the cystoscopic and histopathological findings. All tumours of the urinary bladder identified at fibreoptic cystoscopy were shown on virtual cystoscopy. The best reconstruction results were obtained from data acquired 30 min after injection of contrast medium. The ureteric orifices were not visualized at virtual cystoscopy. These data lead us to conclude that, at present, virtual cystoscopy has not reached the quality of fibreoptic examination and remains restricted to use in specific cases, for example patients with urethral strictures.     

Schwann cells, neurotrophic factors, and peripheral nerve regeneration

The peripheral nervous system retains a considerable capacity for regeneration. However, functional recovery rarely returns to the preinjury level no matter how accurate the nerve repair is, and the more proximal the injury the worse the recovery. Among a variety of approaches being used to enhance peripheral nerve regeneration are the manipulation of Schwann cells and the use of neurotrophic factors. Such factors include, first, nerve growth factor (NGF) and the other recently identified members of the neurotrophin family, namely, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4/5 (NT-4/5); second, the neurokines ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF); and third, the transforming growth factors (TGFs)-beta and their distant relative, glial cell line-derived neurotrophic factor (GDNF). In this review article we focus on the roles in peripheral nerve regeneration of Schwann cells and of the neurotrophin family, CNTF and GDNF, and the relationship between these. Finally, we discuss what remains to be understood about the possible clinical use of neurotrophic factors.     

Cloning using nuclear transfer in bovine species: results and perspectives

A all in vitro cloning technique was developed in which the reconstituted embryos from the first cycle nuclear transfer (cloning) were used as blastomere donor for the second cycle nuclear transfer (recloning). Such method permitted to produce 14.5% of morulae and 14.9% of blastocysts after the first and second cycles of nuclear transfer, respectively. The rates of birth obtained after transfer of such embryos were 21.4% et 20.8% for first and second cycles respectively, corresponding to 6 et 5 calves for 28 et 24 transferred embryos. Unfortunately, gestation pathologies and an increase of birth weights were observed. It seems that the in vitro presence of gametes and/or embryos may be responsible of an alteration in the control of gene expression.     

In vitro maintenance of Leishmania amastigotes directly from lesions: advantages and limitations

Leishmania amazonensis (MHOM/BR/77/LTB0016) amastigotes were obtained from mouse cutaneous lesions and maintained in vitro for 48 hr at pH 4.6, 33 C. These organisms were reproducing, capable of transformation to promastigotes, and did not display the promastigote-specific antigen, GP46. In contrast, 97% of the organisms maintained for 24 hr at 31 C, pH 7.3, were positive for GP46. Thus, short-term cultivation of this L. amazonensis strain under appropriate conditions can provide a high yield of amastigotes for various in vivo and in vitro studies. However, the possible interference of host immunoglobin on the surface of these amastigotes needs to be considered because fluorescent-labeled anti-mouse immunoglobulin was detected on 16% of lesion-derived amastigotes even after 114 hr of cultivation.     

Expression of Kit in neurofibromin-deficient human Schwann cells: role in Schwann cell hyperplasia associated with type 1 neurofibromatosis

Type 1 Neurofibromatosis (NF1) is characterized by the formation of neurofibromas, benign tumors composed mainly of Schwann cells, which can turn malignant to form neurofibrosarcomas. Neurofibromin, the protein product of the Nf1 gene, is believed to act as a tumor suppressor, accelerating the conversion of the oncogene Ras to its inactive form. The absence of neurofibromin could therefore lead to higher Ras activity in Schwann cells, resulting in uncontrolled growth through a cascade of events not yet elucidated. We describe the abnormal expression of high levels of the Kit tyrosine kinase receptor in both NF1-derived Schwann cell lines and tissue, as compared to primary Schwann cells or schwannoma-derived cells. High levels of Kit expression in the neurofibrosarcoma-derived Schwann cells correlate with a decrease in neurofibromin expression. Using inhibitors of tyrosine kinase receptors, we found that proliferation of the neurofibrosarcoma-derived cells is dependent upon activation of a subclass of tyrosine-kinase receptors. The proliferation of these cells is not dependent upon an autocrine loop involving typical Schwann cell mitogens. Finally, the proliferation of the neurofibrosarcoma-derived Schwann cells can be increased by stimulation with Kit ligand. These data implicate Kit as one of the components leading to the Schwann cell hyperplasia observed in NF1.     

The effect of denervated muscle and Schwann cells on axon collateral sprouting

The effects of denervated muscle and Schwann cells on collateral sprouting from peripheral nerve were studied in the peroneal and tibial nerves of 48 Sprague-Dawley rats. Three groups were prepared. In group MSW (muscle-Schwann cell-window), the peroneal nerves were transected 3 mm below the sciatic bifurcation. The proximal stumps were sealed in a blocked tube to prevent regeneration and the distal stumps were implanted into denervated muscle cells that were wrapped around the ipsilateral tibial nerve, which had a window of perineurium resected. Schwann cells from the ipsilateral sural nerve were implanted into the muscle. Group MS (muscle-Schwann cell) was similar to group MSW, except that the tibial nerve perineurium was kept intact. In group MW (muscle-window), the muscle was prepared without Schwann cells and the tibial nerve perineurium was windowed. S-100 immunostain was used to identify the Schwann cells surviving 1 week after transplantation. After 16 weeks of regeneration, horseradish peroxidase tracer was used to label motor neurons and sensory neurons reinnervating the peroneal nerve. Myelinated axons of the reinnervated peroneal nerves were quantified with the Bioquant OS/2 computer system (R&M Biometrics, Nashville, TN). A mean of 169 motor neurons in group MSW, 64 in group MW, and 26 in group MS reinnervated the peroneal nerve. In the dorsal root ganglion, the mean number of labeled sensory neurons was 1,283 in group MSW, 947 in group MS, and 615 in group MW. The mean number of myelinated axons in the reinnervated peroneal nerve was 1,659 in group MSW, 359 in group MS, and 348 in group MW. Reinnervated anterolateral compartment muscles in group MSW were significantly heavier than those in group MS or MW. This study demonstrates that the transplantation of denervated muscle and Schwann cells promotes motor and sensory nerve collateral sprouting through a perineurial window.     

Two perspectives on the validation of developmental constructs: Psychometric and theoretical limitations in research on egocentrism.

Extends the present author's (see record 1980-05161-001) earlier analysis of the egocentrism construct and the psychometrically oriented reanalysis of H. S. Waters and V. S. Tinsley (see record 1985-22354-001) by offering a theoretically focused perspective on the validation of developmental constructs. It suggests that chronic psychometric problems in construct validation research can usually be attributed to underlying theoretical problems. Concrete examples of the limitations of cognitive-developmental theory in guiding research on egocentrism are provided and new theoretical directions are outlined. These alternative explanatory frameworks include, contextual theory developed by D. H. Feldman (1980), the cognitive-processing theory of M. Chapman (1981), and the living-systems theory of D. H. Ford (in press) and the present author (1984). (17 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neurocircuitry of conditioned inhibition of analgesia: effects of amygdala, dorsal raphe, ventral medullary, and spinal cord lesions on antianalgesia in the rat

Pain inhibition (analgesia) is produced by learned danger signals and inhibited by learned safety signals (antianalgesia). Conditioned analgesia is mediated by brain-to-spinal pathways releasing spinal endogenous opiates. Spinal morphine mimics learned danger signals in producing analgesia, which is inhibited by antianalgesia. The circuitry mediating antianalgesia is unknown. These experiments demonstrate that raphe dorsalis, raphe magnus, and spinal dorsolateral funiculus lesions abolish antianalgesia. Other lesions had no effect on antianalgesia. More important, lesions that blocked development of conditioned analgesia did not block development of antianalgesia. Thus, neural circuitries mediating analgesia and antianalgesia were found to be distinct, and conditioned inhibition of analgesia was found to act by inhibiting the most distal part of the conditioned analgesia circuit, namely, the spinal cord.     

Mode of locomotion of Schwann cells migrating in vivo

The manner of locomotion of Schwann cells during normal development was studied by means of repeated observations and photomicrographs of individual cells at closely spaced time intervals and focal levels. In developing tadpole peripheral nerves, Schwann cells move sporadically with brief periods of rapid translation of the whole cell interspersed with longer intervals when the cell shows little or no overall movement. Highest rates of locomotion averaged 5 micrometer/minute with a duration of no greater than four to six minutes. Net rates of speed measured over at least 20 minutes were always considerably lower, with the average being 1.9 micrometer/minute. Rapid locomotion involves protrusion and growth of several pseudopodia, while the cell body remains in place, followed by attachment of these processes to an axonal surface, and finally detachment of the trailing portions of the cell as the entire cell hitches forward, "inchworm-style".     

Pediatric lung transplantation. Indications, techniques, and early results

From July 1990 to April 1993, 36 lung transplantations in 33 patients were performed in our pediatric transplant program (0.25 to 23 years, mean age 10.3 years). Eight children had been continuously supported with a ventilator for 3 days to 4.5 years before transplantation and three were supported by extracorporeal membrane oxygenation. Indications for lung transplantation in this pediatric population included the following: cystic fibrosis (n = 13), pulmonary hypertension, and associated congenital heart disease (n = 10), pulmonary atresia, ventricular septal defect and nonconfluent pulmonary arteries (n = 3), pulmonary fibrosis (n = 6), and acute respiratory distress syndrome (n = 1). Three children underwent retransplantation for acute graft failure (n = 2) or chronic rejection (n = 1). Pulmonary fibrosis was related to complications of treatment of acute of myelogenous leukemia with bone marrow transplantation in two children and to bronchiolitis obliterans, bronchopulmonary dysplasia, interstitial pneumonitis, and Langerhans cell histiocytosis in four others. Thirteen children underwent lung transplantation and concomitant cardiac repair. Bilateral lung transplantation, ventricular septal defect closure and pulmonary homograft reconstruction of the right ventricular outflow tract to the transplanted lungs was performed in three children by means of a new technique that avoids the need for combined heart-lung transplantation. Two patients had ventricular septal defect closure and single lung transplant for Eisenmenger's syndrome, two had ligation of a patent ductus arteriosus and transplantation, three additional children underwent atrial septal defect closure and lung transplantation, and two underwent lung transplantation for congenital pulmonary vein stenosis. Eight early deaths and three late deaths occurred (actuarial 1-year survival 62%). Lung transplantation in children has been associated with acceptable early results, although modification of the adult implantation technique has been necessary. Lung transplantation and repair of complex congenital heart defects is possible; heart-lung transplantation may only be required for patients with severe left heart dysfunction and associated pulmonary vascular disease. Bronchiolitis obliterans remains a major concern for long-term graft function in pediatric lung transplant recipients.     

In utero haematopoietic stem cell transplantation: current perspectives and future potential

In utero transplantation (IUT) of haematopoietic cells is a new therapeutic option for families with increased risk of having a child with an inherited disorder. Immunological naiveté and the rapidly expanding haematopoietic system in the first trimester human fetus, make therapeutic intervention by IUT a real possibility for those disorders which can be diagnosed early in gestation. Fewer cells are required than in postnatal BMT and therapy can be offered before the pathological sequelae of a disorder become manifested. However, only a few cases of IUT have been performed in humans and it is imperative that consensus is reached quickly on issues such as cell numbers/cell types so that the benefits of this approach to treatment can be realised. This review presents the current status of IUT, the cases thus far recorded and offers a prospective view of developments in this rapidly expanding area.