Transplanted pancreatic stem cells can reverse diabetes in mice
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Biomedical subjects
Publications and source records attributed to A Berger.
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The resident macrophages have been accepted as an important component of the peripheral nervous system as Schwann cells. To elucidate their role during Wallerian degeneration without interference from extrinsic hematogenous macrophages, we designed a culture system to investigate the behavior of resident macrophages in vitro. A total of 75 adult male Lewis rats were used; 2. 5-cm-length sciatic nerve explants were harvested. There were three groups. In the culture groups, the nerve explants were incubated in Dulbecco's modified Eagle's medium (DMEM) only or in DMEM supplemented with 2 microm forskolin and 10 microg/ml pituitary extract (mitogenic medium for Schwann cells). In vivo predegenerated nerves and normal nerves were used as the positive and negative controls, respectively. The observation periods extended to 3 weeks. Hematoxylin and eosin (H&E) stain was employed to estimate overall cell number in nerve explants. Macrophages were labeled with ED1; S-100 immunostaining was used to evaluate the presence of Schwann cells during Wallerian degeneration. Trichrome stain and toluidine blue stain were used to visualize the fate of myelin. In the culture groups, the number of resident macrophages increased continuously, although there were significantly fewer resident macrophages than hematogenous macrophages after 3 days of Wallerian degeneration (P < 0.01). Morphologically, resident macrophages contained densely small ED1-positive granules within their cytoplasm, even at later stages of observation, whereas hematogenous macrophages contained typical large ED1-positive foam vacuoles characteristic of their mature phagocytic ability. The cellular activity of Schwann cells was well preserved in the mitogenic medium; however, myelin removal was not significantly enhanced as compared with the DMEM groups (P > 0.05). The clearance of myelin debris was shown to be incomplete in culture groups as compared with the complete removal of myelin debris in the in vivo groups. Resident macrophages were actively involved in Wallerian degeneration, but their phagocytic and proliferation ability was limited. Schwann cells played an adjunctive role during the removal of myelin debris.
We report on our experience with Integra application in 22 patients treated from February 1996 through April 1999. Nine patients suffered a primary burn injury and 13 patients had secondary unstable scars. Integra is artificial skin that consists of a collagen/glycosaminoglycane matrix and a silicon layer. It was first used by Burke and Yannas in 1980 in the USA. The mechanical and biological features of Integra protect the tissue from fluid loss and bacterial invasion in the acutely burned patient. The integra-induced formation of a neodermis leads to functionally and aesthetically highly acceptable scar formation. We present our clinical experience with Integra in long-term follow-up.
We previously reported on a series of 27 newborn infants treated for posthemorrhagic hydrocephalus with external ventricular drainage during 1984 to 1989. In the present study we continued to evaluate this technique during the subsequent 8 years (37 patients; mean birthweight 1251+/-478 g; mean gestational age 29+/-2.9 weeks; 51 drains), and we now report on the long-term experience with this method, complications, and neurodevelopmental outcome of the survivors. The mean age at drain insertion was 21 days, and the mean duration of drainage 23 days. Eight infants died of causes unrelated to external ventricular drainage. Eleven of the survivors did not require a permanent shunt. Two patients experienced ventriculitis, resulting in an infection rate of 5.4% per patient and 3.9% per drain. The neurodevelopmental outcome was mainly dependent on the extent of the pre-existing parenchymal injury. We conclude that external ventricular drainage is a safe and effective technique for the management of preterm infants with posthemorrhagic hydrocephalus.
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OBJECTIVES: The aim of this study was to evaluate the time course of S-100beta and neuron-specific enolase serum levels after cardiac surgery and their clinical relevance in predicting postoperative adverse neurologic outcomes; the 2 proteins are only released in peripheral blood in association with nervous system lesions. METHODS: We neurologically assessed 190 consecutive patients undergoing elective cardiac operations for coronary artery bypass (n = 147), valve replacement (n = 29), or both (n = 14), before as well as after the operation. Postoperative outcome was classified as type I (uncomplicated), type II (confusion, agitation, disorientation, or epileptic seizures), or type III (stroke, stupor, or coma). Levels of S-100beta and neuron-specific enolase were evaluated in venous blood samples drawn preoperatively and then daily in the first 5 postoperative days. RESULTS: Levels of S-100beta and neuron-specific enolase differed significantly among the 3 groups (type III > type II > type I) throughout the postoperative period and had a diagnostic specificity and specificity of 89% and 79%, respectively, in identifying patients with type III outcome. S-100beta (but not neuron-specific enolase) levels were identified as significant independent predictors for type II and III outcomes (odds ratio 16.2, P <.0004). The same was true for duration of cardiopulmonary bypass (odds ratio 1.02, P <.006). CONCLUSIONS: Serum levels of S-100beta are reliable markers for adverse neurologic outcomes after cardiac surgery.
In the last decade, it has been possible to trace the areas of the human brain involved in a variety of cognitive and emotional processes by use of imaging technology. Brain networks that subserve attention have been described. It is now possible to use these networks as model systems for the exploration of symptoms arising from various forms of pathology. For example, we can use the orienting network to understand the effects of lesions that produce neglect of sensory information either by brain damage or by restricting transmitter input. Frontal attention networks may provide similar understanding of pathologies at higher levels of cognition. Evidence relating these networks to attention deficit and hyperactivity disorder (ADHD) is considered.
BACKGROUND: Epidemiological data suggest that chronic hepatitis C virus (HCV) infection may contribute to the development of diabetes mellitus. Therapy of HCV infection with recombinant interferon-alpha (r-IFN-alpha) can also impair of glucose metabolism. METHODS: To investigate the impact of HCV infection and the therapy with r-IFN-alpha on glucose metabolism we measured insulin sensitivity, glucose effectiveness, and first and second phase insulin secretion, using the minimal modelling analysis of frequently sampled intravenous glucose tolerance tests in 13 nondiabetic patients with HCV-induced liver disease before and after therapy with r-INF-alpha (6 x 106 U, subcutaneously, three times a week over 4 months). Liver biopsy was performed to evaluate and score liver fibrosis as a marker of HCV-induced cell injury. RESULTS: Insulin sensitivity (r = - 0.59, P < 0.05) and first phase insulin secretion (r = - 0.66, P < 0.03) were negatively related to the fibrosis score. Insulin sensitivity rose from 1.96 (SEM 0.37, n = 8) to 5.69 (SEM 0.99, n = 8) 10-4 min-1 per microU mL-1 (P < 0.01) in responders and from 2.51 (SEM 0.61, n = 5) to 6.95 (SEM 1.99, n = 5) in nonresponders after 4 months r-INF-alpha therapy. Fasting free fatty acids decreased significantly to about 50% (P < 0.01) in patients with and without therapy response after 4 months, whereas first phase insulin secretion did not change. CONCLUSIONS: HCV-induced liver injury is related to the deterioration of insulin sensitivity and first phase insulin response, thus impairing glucose homeostasis in these HCV-infected patients. The administration of r-INF-alpha three times a week over 4 months is not associated with an impairment of glucose homeostasis.
The effect of physiological stress on the magnitude of inbreeding depression in plants has been the subject of few studies and is currently controversial because of contradictory results. We measured the inbreeding depression at three drought stress levels, precisely defined by a preliminary physiological experiment. We also tested the hypothesis that more highly self-compatible populations exhibit reduced inbreeding depression due to purging of deleterious mutations. The study was conducted on two populations of the annual and allogamous plant Crepis sancta collected from the French Mediterranean region and two other populations from marginal areas with various self-incompatibility levels. Drought stress did not increase inbreeding depression in terms of plant mortality but significantly increased the inbreeding depression for the date of first flowering, number of heads per plant and relative growth rate. The most self-fertile marginal population showed an absence of inbreeding depression in most of the measured traits indicating that purging could have taken place in this population. The three others populations showed relatively low and similar estimates of inbreeding depression (delta approximately 0.35). The relatively low values obtained compared to the results found in allogamous plants suggests that the absence of competition for C. sancta in our experiment probably underestimated the effects of inbreeding in natural populations where competition occurs.
Self-inflicted disorders of wound healing were diagnosed in two women (aged 24 and 25 years) after long years of history. A detailed medical history and the characteristic course helped to confirm the diagnosis. The artificial wounds were an expression of a severe psychic disturbance in both young women. Operative therapy was able to restore the local findings, the basic psychological disorder required a long-term psychotherapeutic treatment to prevent irreversible, partially iatrogenic co-induced somatic mutilations, due to an exceptionally high recurrence rate.
In a retrospective study, including 60 patients, after free latissimus dorsi transplantation (FLDT) to the lower leg, we found persistent pedicle blood flow up to ten years postoperatively. After uncomplicated FLDT, the pedicle supported the flap in all cases. After complicated FLDT (hematoma, thrombosis, infection) only 50% of all flaps after ten years were perfused by the vascular pedicle.
The necessity for routine angiography in evaluation of the vasculature of recipient legs prior to microsurgical free-tissue reconstruction still remains controversial. This prospective study was designed to determine the indications and limitations of angiography pertinent to this issue. The protocol consisted of palpation of dorsalis pedis and posterior tibial artery pulsation and lower-limb angiography prior to surgery, as well as intraoperative observation of the posterior tibial, anterior tibial, and peroneal arteries. Thirty-six patients were included who were treated from November, 1993 to December 1998. In five patients either the posterior tibial pulse (1), the dorsalis pedis pulse (3), or both pedal pulses, including the popliteal pulse (1) were not palpable preoperatively. These clinical findings correlated with the vascular lesion images on angiography. In two patients, pedal pulse palpation could not clearly be evaluated because of the injury. Among the 29 patients with both pedal pulses palpable, three patients angiographically presented an injury of the peroneal artery, and one patient a pseudoaneurysm of the anterior tibial artery. In none of the cases with at least one palpable pedal pulse (33), did preoperative angiography add relevant information which led to a plan change in the free-flap transfer. However, in two cases, severe scarring and fibrosis required an intraoperative change of the recipient vessel in one case, and a change of the anastomosis level and use of a vein graft, in the other case, although the angiography had demonstrated normal vascularity in both. The authors conclude that preoperative angiography is indicated only when both pedal pulses are not palpable, and that normal preoperative angiography does not guarantee the presence of vessels suitable for anastomosis.
The aim of this study was to obtain further insights about muscle regeneration processes in free neurovascular flaps. In cases of insufficient functional return of muscle strength, several factors, such as diminished axonal ingrowth, fatty degeneration, or connective tissue proliferation are discussed. In the study, free neurovascular latissimus dorsi (LD) flaps were examined after a regeneration period of 2 to 6 years. Clinical function (M1 to M4) and histopathologic characteristics of the muscle grafts were correlated. The rare instances of secondary procedures, such as tenolysis or scar correction, were used for biopsies of the muscle graft. Free neurovascular LD flaps were examined after a regeneration period between 2 and 6 years. The grafted LD was compared to normal, healthy LD muscle. Normal LD muscle showed a typical homogeneous pattern of types 1 and 2 fibers in a ratio of almost 1:1. No significant differences concerning fiber distribution and fiber diameters in three anatomic areas of the LD (proximal, medial, caudal) could be detected. After regeneration, the authors found the following: type grouping of muscle fiber types, fiber splitting, and groups of hypertrophic and atrophic fibers. Most of the muscle fibers were not reinnervated by axons and were atrophic or degenerated. The essential proliferation of connective and fatty tissue was absent. Normal and hypertrophic fibers were found mainly in the muscle grafts with good clinical results. In muscle grafts with good contraction force (M4), 46 percent of reinnervated muscle fibers were found; M3 contractility was correlated with 31 percent of reinnervated muscle fibers; M2 with 24 percent; and M1 with 21 percent of reinnervated fibers. The force of a free muscle graft seems to depend mainly on the quality of nerve regeneration. Characteristics of the muscle fiber itself were not examined extensively, because the single-fiber contractility of the regenerated fibers was similar to the contractility of normal, healthy fibers.