Adrenoleukodystrophy in a Chinese boy.

We report the first Chinese boy with adrenoleukodystrophy (ALD) who presented with hyperpigmentation, behavioral change and demyelination shown in magnetic resonance imaging of the brain. ALD was confirmed by the elevation of very long chain fatty acid in the serum and biochemical evidence of adrenal insufficiency. A trial of special diet with restriction of very long chain fatty acid and addition of glyceryl trierucate/glycerol trioleate oil (GTEO or Lorenzo's oil) failed to prevent clinical deterioration. The child had progressive visual loss and spastic tetraparesis despite dietary manipulation, adrenal steroid replacement and intravenous gammaglobulin treatment.     

SRTR Center-Specific Reporting Tools: Posttransplant Outcomes

Measuring and monitoring performance—be it waiting list and posttransplant outcomes by a transplant center, or organ donation success by an organ procurement organization and its partnering hospitals—is an important component of ensuring good care for people with end-stage organ failure. Many parties have an interest in examining these outcomes, from patients and their families to payers such as insurance companies or the Centers for Medicare and Medicaid Services; from primary caregivers providing patient counseling to government agencies charged with protecting patients.
The Scientific Registry of Transplant Recipients produces regular, public reports on the performance of transplant centers and organ procurement organizations. This article explains the statistical tools used to prepare these reports, with a focus on graft survival and patient survival rates of transplant centers—especially the methods used to fairly and usefully compare outcomes of centers that serve different populations. The article concludes with a practical application of these statistics—their use in screening transplant center performance to identify centers that may need remedial action by the OPTN/UNOS Membership and Professional Standards Committee.     

Rectus sheath haematoma requiring laparotomy

Rectus sheath haematoma is a well‐documented but unusual cause of acute abdomen. Combination of clinical features and appropriate radiological investigations can make for a prompt diagnosis. Most authors advocate conservative management and it has been reported that patients were directly discharged from the emergency department. We report a case of rectus sheath haematoma which progressed with clinical deterioration and necessitated surgical intervention for clot evacuation. Causes, physical signs, radiological features and classification of rectus sheath haematoma are discussed. It may be necessary to continue close clinical monitoring after diagnosis of rectus sheath haematoma.     

Hemodynamic disturbances associated with endovascular embolization in newborn infants with vein of Galen malformation.

OBJECTIVE: To examine hemodynamic changes following endovascular embolization in newborn infants with vein of Galen malformation and severe cardiac failure in the first week of life. STUDY DESIGN: Over a recent 5-year period, nine such infants were identified. In seven of these infants, changes in arterial blood pressure were analyzed in relation to the timing of embolization procedures. RESULTS: A significant increase in arterial blood pressure was noted after most embolizations. In two infants, this systemic hypertension was severe and treated using intravenous antihypertensive drugs. Both infants subsequently developed complete infarction of both cerebral hemispheres with sparing of the brainstem and cerebellum. Mortality in the nine infants was 33%, and 83% of the survivors were neurologically normal or near normal at follow-up. CONCLUSION: The systemic hypertension observed following endovascular embolizations may provide a protective mechanism to maintain cerebral blood flow after reperfusion injury. Lowering blood pressure in this situation may therefore be detrimental.     

Improved purification and characterization of hemolysin BL, a hemolytic dermonecrotic vascular permeability factor from Bacillus cereus.

Bacillus cereus causes diarrheal and emetic food poisoning syndromes as well as a variety of mild to severe infections. A dermonecrotic vascular permeability (VP) factor has been implicated as a virulence factor in these illnesses. Hemolysin BL was previously identified as a unique tripartite hemolysin possessing VP activity. In this study, a high-yield purification scheme, which allowed quantitative characterization of hemolysin BL activity and determination of the molecular weight, pI, and N-terminal sequence of each component, was developed. Milligram quantities of the B, L1, and L2 components were highly purified by a combination of anion-exchange and hydroxylapatite chromatographies. The combined components had VP activity at low doses and were necrotic at higher doses. The toxin exhibited an unusual dose-response zone phenomenon in turbidometric hemolysis assays. Activity increased at doses up to 200 ng/ml, then decreased at doses up to 350 ng/ml, and was constant at doses up to at least 2,500 ng/ml. This behavior may provide an explanation for the unusual discontinuous pattern typical of hemolysin BL in gel diffusion assays. At high concentrations of one or two components, the presence of low amounts of the complementary component(s) resulted in full hemolytic activity. Erythrocytes were protected from lysis by Zn2+ at micromolar concentrations but not by Ca2+ and Mg2+ at concentrations up to 25 mM. These data provide guidelines for future work on this toxin and indicate that hemolysin BL is the dermonecrotic VP factor implicated as a B. cereus virulence factor.     

Dopamine transporter imaging with novel, selective cocaine analogs.

RTI-121 and RTI-122 are 3 beta-substituted phenyltropane analogs of cocaine that have high, selective binding affinity for dopamine transporters. [123I]RTI-121 and [123I]RTI-122 bind to dopamine transporters in vivo after intravenous administration and permit imaging of the transporters.     

Management of metastatic breast cancer

Systemic treatment almost certainly prolongs the median survival of women with metastatic breast cancer, and it may prolong the survival of a small number of patients substantially. Even with conventional therapy, 10% or more patients may live into the second decade after recurrence. However, the disease cannot be eradicated, and the primary goal of treatment remains palliation and improvement of the quality of life. Because of the great variability in the pattern and course of the disease from one patient to another, therapy should be selected judiciously to maximize response and minimize toxicity. In some clinical situations, such as pathologic fractures and brain metastases, local therapies alone, such as surgery or irradiation, are the treatments of choice. Patients who will respond to endocrine therapy are well defined, and all patients with the characteristics of an endocrine responder deserve a chance at palliation with this modality alone because of its limited toxicity. A number of new forms of endocrine therapy with more specific targets at estrogen and progesterone receptor sites are now in clinical trials. When used appropriately, chemotherapy significantly improves patient quality of life despite its toxicity. No drug combinations, schedules, or doses have been shown to prolong survival or provide better net palliation than classic CMF (oral cyclophosphamide with intravenous methotrexate and 5-fluorouracil) or CAF (intravenous cyclophosphamide, doxorubicin, and 5-fluorouracil). Treatment with these combinations in excess of 6 to 9 months provides only marginal additional benefits and no survival advantage. The role of high dose chemotherapy with autologous bone marrow transplantation remains a promising area of investigation, but the available survival data are entirely compatible with the possibility that this modality will eventually prove inferior to conventional therapy. Many new cytotoxic agents with unique mechanisms of action are currently under investigation, including taxol, taxotere, Topotecan, and amonafide. Taxol may be the most promising therapy now available for patients whose disease has become refractory to doxorubicin. Biologic therapies using monoclonal antibodies against a specific oncogene or its product have entered clinical trials, and novel drug delivery systems using liposomes are under evaluation.

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Resumen El tratamiento sistémico casi ciertamente prolonga la supervivencia media de las mujeres con cáncer mamario metastásico y logra prolongar la sobrevida de un muy pequeño número de pacientes en forma muy sustancial. Aún con terapia convencional, 10% o más de las pacientes sobreviven hasta la segunda década después de una recurrencia. Sin embargo, la enfermedad no puede ser erradicada y el objetivo primario del tratamiento sigue siendo paliativo para mejorar la calidad de vida. Teniendo en cuenta la gran variabilidad del patrón y de la evolución de la enfermedad entre una y otra paciente, la terapia debe ser cuidadosamente seleccionada a fin de lograr la máxima respuesta y minimizar la toxicidad. En algunas situaciones clínicas, tales como las fracturas patológicas y las metástasis cerebrales, las solas modalidades de terapia local, tales como la cirugía o la irradiación, constituyen los tratamientos de elección. Las pacientes que puedan responder a la terapia endocrina están bien definidas, y todas las pacientes con las características de ser una de las que responda al manejo endocrino merece la oportunidad de paliación con esta modalidad, en virtud de su limitada toxicidad. Variadas y nuevas formas de terapia endocrina con miras más específicas en cuanto a receptores de estrógeno y de progesterona se encuentran en ensayo. Cuando la quimioterapia es utilizada en forma apropiada, ésta mejora significativamente la calidad de vida a pesar de su toxicidad. Ninguna combinación de drogas, programas o dosificaciones ha demonstrado prolongar la sobrevida o lograr mejor paliación que el régimen clásico CMF (ciclofosfamida oral con metotrexato IV y 5-fluorouracilo). El tratamiento con estas combinaciones por más de 6–9 meses provee apenas beneficios adicionales marginales y ninguna ventaja en cuanto a sobrevida. El papel de la quimioterapia de altas dosis con trasplante autólogo de médula ósea permanece como una promisoria área de investigación, pero la información sobre supervivencia hasta ahora disponible es enteramente compatible con la posibilidad de que esta modalidad llegue a demostrar ser inferior a la terapia convencional. Muchos nuevos agentes citotóxicos con mecanismos de acción únicos están siendo investigados en la actualidad. Estos incluyen el taxol, el taxotere, el Topotecan y el amonafide. El taxol puede ser la forma más promisoria de terapia actualmente disponible para pacientes cuya enfermedad se ha hecho resistente a la doxorubicina. Las terapias biológicas usando anticuerpos monoclonales contra un oncogene específico o su producto han ingresado a los ensayos clínicos y novedosos sistemas de administración de drogas, utilizando liposomas, también se hallan en proceso de investigación.

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Résumé Le traitement par voie systémique prolonge la survie médiane des patientes ayant un cancer métastatique du sein et peut également prolonger, sans doute, la survie d'un petit nombre d'autres patientes quel que soit le dégréé de sévérité de la maladie. Même avec une thérapeutique conventionnelle, 10% ou plus des patientes peuvent espérer survivre plus de 10 ans après leur récidive. La maladie ne peut, dans ce cas cependant, être enrayée et le but de la thérapeutique restera palliatif et d'améliorer la qualité de vie. En raison de la grande variabilité du type et de l'évolutivité de la maladie d'une patiente à l'autre, chaque protocole thérapeutique se doit d'être élaboré de façon à maximaliser la réponse tout en minimisant la toxicité. Dans certaines situations cliniques, telles les fractures pathologiques ou les métastases cérébrales, les thérapeutiques locales, telles la chirurgie ou l'irradiation, sont de modalités thérapeutiques de choix. On connaît aussi une catégorie de patientes qui répondent bien au traitement hormonal, qui devraient toutes être traitées par cette modalité étant donnée le peu de toxicité. Un certain nombre de ces traitements hormonaux sont actuellement l'objet d'essais thérapeutiques. Utilisée judicieusement la chimiothérapie améliore de façon significative la qualité de vie, et ce souvent, malgré sa toxicité. Aucune combinaison de médicaments ni de régimes ou de doses ne se sont montrés plus efficaces pour prolonger la survie ou améliorer le confort mieux que la classique association CMF (cyclophosphamide per os, methotrexate et 5-Fluorouracil par voie intraveineuse) ou la CAF (cyclophosphamide, doxorubicine, 5-fluorouracil par voie intraveineuse). Un traitement par ces combinaisons pendant plus de 6–9 mois n'apporte guère d'avantages, sans prolonger la survie pour autant. Le rôle de la chimiothérapie à hautes doses combinée avec la greffe de moelle osseuse était une voie prometteuse mais pour le moment, il semble exister de preuves en faveur de son infériorìté par rapport aux traitements conventionnels. D'autres nouvelles substances cytotoxiques, faisant intervenir d'uniques mécanismes d'actions, sont actuellement en cours d'évaluation. Ces nouveaux médicaments comprennent le taxol, le taxotère, le Topotécane, et l'amonafide. Le taxol est probablement celuì qui a le plus d'intérêt, semble-t'il, e cas de résistance à la doxorubicine. Des traitements biologiques, utilisant des anticorps spécifiques dirigés contre tel on tel oncogèn ou son produit, ainsi que de nouveaux systèmes d'apport des médicaments sont également au stade d'évaluation clinique.

     

Extracellular ATP induces rapid cell rounding in cultured human Chang liver cells.

Extracellular ATP (7 microM-14 mM) induced monolayer Chang liver cells (ATCC CCL 13) to retract and round up in dose-dependent and time-dependent manners. ATP-induced rounding was concomitant with raised intracellular pH (7.3 to 7.8) and suppressed (a) in sodium-free medium (250 mM sucrose), (b) with the addition of 1 mM quinidine, an inhibitor of Na+/H+ exchanges, and (c) with the addition of 10 nM staurosporine, a potent inhibitor of protein kinase C that is known to activate Na+/H+ exchanges. These findings suggest that ATP-induced cell rounding is due to activation of Na+/H+ antiporters.     

Inhaled budesonide aerosols in treatment of childhood asthma

Twenty-six children with chronic bronchial asthma, 19 boys and 7 girls, aged between 6 and 16 years with duration of asthma ranging from 1-12 years, were studied by a control, oral prednisolone 5 mg twice a day and inhaled budesonide 200 micrograms twice daily, each for 3 weeks. The clinical efficacy assessed daily by day and night symptom scores of cough, wheeze, sleep disturbance, limitation of activity, symptomatic inhaled terbutaline usage, daily morning and afternoon Peak Expiratory Flow Rate (PEFR), and weekly PEFR and Forced Expiratory Volume in 1 second (FEV1) in percent of predict, showed statistically significant improvement during the inhaled budesonide aerosol and oral prednisolone treatment periods in comparison with the control. No side effect was observed during any study periods.