Serial in vivo MR tracking of magnetically labeled neural spheres transplanted in chronic EAE mice.

Neural stem cell (NSC) transplantation has been shown to attenuate the severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Central to the future success of NSC transplantation in MS is the ability of transplanted cells to migrate from the site of transplantation to relevant foci of disease. Using magnetically labeled mouse neurospheres and human embryonic stem cell (hESC)-derived neurospheres, we applied serial magnetic resonance imaging (MRI) to assess the biodynamics of transplanted cell migration in a chronic mouse EAE model. Magnetic labeling did not affect the in vitro and in vivo characteristics of cells as multipotential precursors. Cell migration occurred along white matter (WM) tracts (especially the corpus callosum (CC), fimbria, and internal capsule), predominantly early in the acute phase of disease, and in an asymmetric manner. The distance of cell migration correlated well with clinical severity of disease and the number of microglia in the WM tracts, supporting the notion that inflammatory signals promote transplanted cell migration. This study shows for the first time that hESC-derived neural precursors also respond to tissue signals in an MS model, similarly to rodent cells. The results are directly relevant for designing and optimizing cell therapies for MS, and achieving a better understanding of in vivo cell dynamics and cell-tissue interactions.     

Corridor4DM: the Michigan method for quantitative nuclear cardiology.

Quantitative software for the analysis and review of myocardial perfusion emission computed tomography images is an indispensable tool in the nuclear physician's evaluation of patients with known or suspected heart disease. The Corridor4DM (4DM) application (formerly known as 4DM-SPECT), developed at the University of Michigan Medical Center, is a quantitative software application providing automated processing, analysis, and reporting of myocardial perfusion and function from cardiac emission computed tomography studies in a tightly integrated, user-centered environment. With health care placing increased emphasis on higher quality and efficiency in diagnostic imaging, quantitative analysis and review software applications need to provide a comprehensive environment supporting correlative review of multimodality images, integrated report generation, and remote review capabilities. The current and future design capabilities of the 4DM software application are discussed with respect to the changing landscape of imaging, where cardiac computed tomography, positron emission tomography, structured reporting, and remote review are expanding the base requirement specifications for quantitative software.     

Use of antibiotic and analgesic drugs during lactation.

During lactation, multiple situations can arise that require maternal pharmacological treatment. Because of the many health advantages of human milk to infants, breast feeding should be interrupted only when the needed drug might be harmful to the nursing child and exposure via the breast milk will be sufficient to pose a risk. Since the majority of drugs have not been shown to cause adverse effects when used during lactation, and even temporary interruption of breast feeding can be difficult for the nursing dyad, decisions regarding maternal medication use during breast feeding should be based on accurate and up-to-date information. This article reviews available data on the most commonly used antibiotics and analgesics. The use of most antibiotics is considered compatible with breast feeding. Penicillins, aminopenicillins, clavulanic acid, cephalosporins, macrolides and metronidazole at dosages at the low end of the recommended dosage range are considered appropriate for use for lactating women. Fluoroquinolones should not be administered as first-line treatment, but if they are indicated, breast feeding should not be interrupted because the risk of adverse effects is low and the risks are justified. Paracetamol (acetaminophen), low-dose aspirin (acetylsalicylic acid) [up to 100 mg/day] and short-term treatment with NSAIDs, codeine, morphine and propoxyphene are considered compatible with breast feeding. Safer alternatives should be considered instead of dipyrone, aspirin at a dosage >100 mg/day and pethidine (meperidine). In the light of the many safe alternatives for pain control, breast-feeding mothers should not be allowed to experience pain or be made to feel that they must choose between analgesia and breast feeding.     

Treatment of perianal infection following bone marrow transplantation

PURPOSE: Bone marrow transplantation (BMT) is often associated with profound neutropenia. Allogeneic transplant recipients also have defects in both humoral and cellular immunity and thus are subject to increased risk of serious, often life-threatening, infection even beyond the period of granulocyte recovery. The current study was undertaken to evaluate patients who required operative intervention for perianal sepsis following BMT. METHODS: The bone marrow transplant database at a single institution was used to identify all patients diagnosed with perianal infections after autologous or allogeneic BMT. Charts were reviewed in a retrospective manner. RESULTS: Over a ten-year period ending in November 1993, 963 BMT were performed at the City of Hope National Medical Center. Twenty-four patients were diagnosed with perianal infections foEowing their transplants. Fifteen patients did not have purulent collections requiring drainage and were treated with antibiotics and supportive measures alone. Nine patients (37.5 percent) required surgical intervention between 10 and 380 days following transplantation. At the time of surgical intervention, seven patients had purulent collections and two patients had acute and chronic inflammation, tissue necrosis, and fibrosis. Of the two patients with an absolute neutrophil count less than 1,000, a purulent collection was found in one of the patients. Cultures taken from perianal abscesses were almost all polymicrobial, and the most common organisms were Escherichia coli, Bacteroides, Enterococcus,and Klebsiella.For those patients undergoing surgical intervention, mean time to complete wound closure by secondary intention was 37.6 days; five patients healed in less than 15 days, two patients healed at 93 and 114 days, and two patients had persistent, open wounds at time of death, which was unrelated to their perianal disease. Five patients were receiving systemic steroids at time of surgical intervention; this did not appear to affect time to wound healing. CONCLUSIONS: Perianal infections are a rare complication of BMT. Majority of these infections are polymicrobial, and organisms isolated are similar to those seen in the perianal infections of nonimmunosuppressed patients. Despite steroid use, granulocytopenia does not exclude the possible presence of purulent collections, and clinical examination should guide the decision for surgical drainage. In general, perianal wound healing is not prolonged in BMT patients.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Montreal, Quebec, Canada, May 7 to 12, 1995.     

Complications of choledochal cysts in adulthood

Choledochal cyst is a well-recognised entity, presenting primarily in infants and young children. Where symptoms are delayed until adulthood, associated hepatobiliary pathology may complicate the presentation. These problems may be aggravated by previous treatment with bypass surgery rather than resection. We report seven cases from our recent experience presenting with complications in adulthood. These included cholangitis, hepatic abscess, pancreatitis and malignancy within the cyst. Two patients presented during pregnancy. These complications and their implications for management are discussed.     

HELLP syndrome associated with factor V R506Q mutation

The pathogenesis of HELLP (haemolysis, elevated liver enzyme and low platelet count) syndrome, a severe presentation of pre-eclampsia, is still an enigma. Activated protein C resistance resulting from a mutation in coagulation factor V has recently emerged as the leading cause of thrombosis in pregnancy. We report on two patients with HELLP syndrome who were found to be heterozygous for factor V R506Q mutation, leading to activated protein C resistance. These findings suggest that the pathogenesis of HELLP syndrome is associated with a thrombotic process, and point to the potential benefit of anti-thrombotic therapy in this condition.     

Use of current situational information and causal inference: Do dysphoric individuals make “unwarranted” causal inferences?

According to Beck's original theory, depressives make unwarranted negatively biased personal inferences. Specifically, Beck suggested that depressives ignore current positive situational information and are unduly influenced by current negative situational information in making inferences. To test Beck's theory, we used Kelley's normative model of causal inference to examine the utilization of causally relevant situational information by dysphoric, nondepressed, and very nondepressed subjects in making causal attributions for personal success and failure. We used Stevens and Jones' classic method from social psychology and embedded the relevant causal information in the natural flow of events. Results showed that dysphoric, nondepressed, and very nondepressed subjects did, to an equal degree, use such information to make causal attributions. Although dysphoric and both groups of nondepressed subjects used current situational information consistently with Kelley's model, clear-cut baseline differences in the content of their causal attributions existed. Thus, the results supported the reformulations of Beck's theory that emphasize content, rather than process, differences between depressive and nondepressive cognition for dysphoria.Preparation of this article was supported by a Vilas Award, a University of Wisconsin Graduate School Grant, a Romnes Fellowship, a Biomedical Grant, and NIMH Grant R01MH43866 to Lyn Y. Abramson.     

The effect of endothelium-derived nitric oxide on ex vivo whole blood platelet aggregation in man

Summary The effects of changes in endogenous endothelium-derived nitric oxide (NO) on forearm blood flow and ex vivo platelet aggregation have been studied in 7 healthy volunteers.Measurements were made of forearm blood flow and ex vivo collagen-stimulated platelet aggregation during unilateral brachial artery infusions of saline, acetylcholine (ACh), N^G monomethyl-L-arginine (L-NMMA), and prostacyclin (PGI₂). The uninfused arm acted as a control.Forearm blood flow was increased by ACh, an agent which stimulates NO release, and decreased by L-NMMA, an agent which stereospecifically inhibits NO synthesis.Collagen-stimulated platelet aggregation measured ex vivo in whole blood draining the infused arm was unaltered by either ACh or L-NMMA. Conversely, PGI₂, an agent which acts independently of NO, caused an increase in forearm blood flow which was accompanied by significant inhibition of platelet aggregation.The results suggest that release of endothelium-derived NO in quantities sufficient to cause substantial changes in blood vessel tone does not lead to changes in platelet aggregation in the blood flowing through the vessels. It is, however, still possible that endothelium-derived NO modulates platelet activity at the level of the endothelium. Present address: Department of Medicine and Therapeutics, University of Aberdeen Polwarth Building, Forrester Hill, Aberdeen, UK