Allogeneic marrow transplantation for children with juvenile chronic myelogenous leukemia

Fourteen children between the ages of 2 and 5 years with juvenile chronic myelogenous leukemia were given cyclophosphamide, total-body irradiation, and marrow transplants. Unmodified marrow was given to six patients who received marrow from HLA-identical siblings and eight patients who received marrow from family members HLA identical for one haplotype but mismatched for one to three loci on the nonshared haplotype. Five patients died of transplant-related complications, and three relapsed at 48, 81, and 1,670 days posttransplant and died of leukemia. Six patients survive in continuous remission from 0.5 to 11.5 years posttransplant.     

Analysis of phorbol ester stimulated human megakaryocyte development

Megakaryocytes are relatively rare components of human bone marrow, making the study of their maturation difficult. Phorbol esters can act as differentiating agents in a number of cell systems including murine megakaryocytes. We report the effects of phorbol esters on the previously described long-term human megakaryocytic leukemia cell culture, EST-IU. While two nontransforming phorbols fail to affect these cells, the transforming phorbol 12-O-tetradecanoylphorbol-13- acetate (TPA) induces a phenotype with characteristics of more mature megakaryocytes in a dose-related manner. This phenotype includes an increased adherence to untreated plastic or glass, polyploidization, an increase in cell size, and increased expression of both platelet glycoproteins and factor VIII-related antigen. Two-color flow cytometric analysis allowed simultaneous determinations of DNA content and the expression of surface membrane antigens or alpha-granule constituents, providing evidence that nuclear, membrane, and cytoplasmic maturation occur in parallel in this cellular system. TPA- induced maturation of EST-IU cells provides an important new cellular model for the further study of human megakaryocyte development.     

The risks of central nervous system relapse and leukoencephalopathy in patients receiving marrow transplants for acute leukemia

The records of 415 patients who received allogeneic marrow transplants for acute leukemia were reviewed to assess the risk of central nervous system (CNS) relapse and leukoencephalopathy after marrow transplantation. The Kaplan-Meier estimates of the probability of CNS relapse posttransplant were 13% for patients with acute lymphoblastic leukemia (ALL) and 2% for patients with acute nonlymphoblastic leukemia (ANL). Previous CNS disease was significantly correlated with an increased risk of CNS relapse in patients transplanted for ALL but not for ANL. In contrast, bone marrow involvement with leukemia at the time of transplant was associated with an increased risk of CNS relapse in patients with ANL but not in patients with ALL. Seventy-one patients with ALL did not receive posttransplant intrathecal methotrexate (IT- MTX) and 127 did. The probability of CNS relapse in these two groups was 38% and 7%, respectively (P less than .02). This protective benefit from IT-MTX was present in patients both with and without a history of CNS involvement or marrow involvement at the time of transplant. In patients with ANL, 116 patients did not receive posttransplant IT-MTX and 101 patients did, but no protection from CNS relapse was observed from IT-MTX irrespective of a patient's previous CNS history or marrow status at the time of transplant. Leukoencephalopathy was seen exclusively in patients who had received radiation and/or intrathecal chemotherapy to the CNS before preparation for marrow transplantation and posttransplant IT-MTX. In such patients the risk of leukoencephalopathy was 7%. From our data, it appears that posttransplant IT-MTX is a significant benefit for ALL patients in preventing CNS relapse after marrow transplantation. A similar benefit from posttransplant IT-MTX for ANL patients cannot be established from this study. In both groups, increasing total CNS therapy was associated with an increasing risk of leukoencephalopathy.     

Activation of the kallikrein-kinin system after endotoxin administration to normal human volunteers

The objective of this study was to determine the role of the kallikrein- kinin system in healthy humans after intravenous administration of either Escherichia coli endotoxin or saline. We studied a total of 18 healthy nonsmoking volunteers, 23 to 38 years old, in an open-label study at the Critical Care Medicine Department, Clinical Center, National Institutes of Health (Bethesda, MD) in which some of the patients served as their own controls. After baseline data collection, the subjects received intravenously either E coli endotoxin (n = 15, 4 ng/kg of body weight) or saline (n = 8, controls). Signs, symptoms, systemic blood pressure, factor XII, plasma prekallikrein (PK), factor XI (FXI), antithrombin III (AT-III), high molecular weight kininogen (HK), and alpha 2-macroglobulin-kallikrein complexes were measured at baseline and 1, 2, 3, 5, and 24 hours after injection of either saline or endotoxin. After infusion of endotoxin, we found the functional plasma levels of FXI decreased at 2 hours (P < .05) and at 5 hours (P < .05). Functional PK was significantly depressed by 2 hours (P < .05), at 5 hours (P < .05), and at 24 hours (P < .01), whereas the PK antigen was only low at 5 hours (P < .05). These changes were accompanied by a significant increase in circulating alpha 2-macroglobulin-kallikrein complexes at 3 hours (P < .05) and 5 hours (P < .01). No significant changes occurred in the plasma levels of factor XII or HK. We concluded that clinical response to intravenous endotoxin in healthy human volunteers is associated with activation of the kallikrein-kinin systems. Further investigation is needed with specific inhibitors of the kallikrein-kinin system to define its primary or secondary role in the endotoxin-mediated reactions.     

Novel non-resorbable polymeric-nanostructured scaffolds for guided bone regeneration

Clinical Oral Investigations - The aim of this study was to evaluate the bone-regeneration efficiency of novel polymeric nanostructured membranes and the effect of zinc, calcium, titanium, and bone...     

A reliable frozen section technique for basal cell carcinomas of the head and neck

Basal cell carcinomas (BCCs) of the head and neck treated by conventional techniques of surgical excision, curettage, cryotherapy and radiation therapy have recurrence rates of up to 42%. Mohs micrographic surgery (MMS) decreases the recurrence rate but can be expensive, delay definitive reconstruction and is limited in its availability.The authors report a series of 50 patients with head and neck BCCs treated by a surgeon-directed ‘en face’ frozen section technique that immediately evaluates the entire peripheral and deep margins during BCC resection, and potentially offers a more efficient and equally effective alternative to MMS.Patient demographics, pathology results, operative time, technique and outcomes are all reported. With a mean follow-up of three years, there was only one recurrence (1.7%). Mean total operative time was 1 h 47 min. The authors conclude that this surgeon-directed ‘en face’ frozen section technique does not require any specialized training, enables more rapid and reliable results than standard frozen section techniques that are currently used, and provides outcomes equivalent to MMS in the surgical treatment of head and neck BCCs.     

Early-onset colorectal cancer: A separate subset of colorectal cancer

Colorectal cancer (CRC) has a great impact on the world population. With increasing frequency, CRC is described according to the presenting phenotype, based on its molecular characteristics. Classification of CRC tumors according to their genetic and/or epigenetic alterations is not only important for establishing the molecular bases of the disease, but also for predicting patient outcomes and developing more individualized treatments. Early-onset CRC is a heterogeneous disease, with a strong familial component, although the disease is sporadic in an important proportion of cases. Different molecular alterations appear to contribute to the apparent heterogeneity of the early-onset population and subgroups can be distinguished with distinct histopathologic and familial characteristics. Moreover, compared with late-onset CRC, there are characteristics that suggest that early-onset CRC may have a different molecular basis. The purpose of this review was to analyze the current state of knowledge about early-onset CRC with respect to clinicopathologic, familial and molecular features. Together, these features make it increasingly clear that this subset of CRC may be a separate disease, although it has much in common with late-onset CRC.     

Is ictal cognitive dysfunction predictable?

Objective

Accurate prediction of electrographic seizure onset may reduce injuries and improve quality of life in pharmaco-resistant epileptics. However, because sub-clinical, far out-number clinical seizures, indiscriminate issuance of warnings may have a paralyzing effect on these patients. This study investigates the predictability of ictal cognitive dysfunction.

Methods

Latency and percentage of correct responses to a reaction time test triggered by automated seizure detections were compared to those obtained inter-ictally in 14 subjects undergoing surgery evaluation. Since accurate prediction of seizures is elusive, early detection was used, as it indirectly but reliably investigates for the existence of a cognitive pre-ictal state.

Results

Significant differences between ictal and inter-ictal cognitive performance were not uncovered until late into the temporal evolution of “focal” seizures.

Conclusions

These observations suggest that cognitive dysfunction is unpredictable in seizures originating from discrete cortical regions, as the transition into unawareness seems abrupt.

Significance

Prediction of electrographic seizure onsets with worthwhile accuracy would likely result in large numbers of daily warnings, the great majority for sub-clinical seizures. This outcome would considerably increase, without safety justification, patients’ psychological burden inherent to each forecast, thus further diminishing quality of life.     

Control of blood pressure levels in patients with premature coronary artery disease: Results from the Genetics of Atherosclerotic Disease study

High blood pressure (BP) is the major cardiovascular‐risk factor for coronary artery disease (CAD), principally in young patients who have an important and increasing socioeconomic burden. Despite the Seventh Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC‐7), recommended BP target <140/90 mm Hg for patients with stable CAD, in 2017 the American College of Cardiology and the American Heart Association (ACC/AHA) updated BP target to <130/80 mm Hg. We aimed to analyze the prevalence of BP control in patients with premature CAD using both criteria. In addition, antihypertensive therapy, lifestyle, clinical, and sociodemographic characteristics of the patients were evaluated in order to identify factors associated with the achievement of BP targets. The present study included 1206 patients with CAD diagnosed before 55 and 65 years old in men and women, respectively. Sociodemographic, clinical, and biochemical data were collected. The results indicate that 85.6% and 77.5% of subjects with premature CAD achieved JNC‐7 non‐strict and ACC/AHA strict BP target, respectively. Consistently, number of antihypertensive drugs and hypertension duration >10 years were inversely associated with BP targets, whereas total physical activity and smoking were directly associated with BP targets, regardless of BP criteria. Considering that age, gender, and hypertension duration are non‐modifiable cardiovascular‐risk factors, our results highlight the need for more effective strategies focused on increase physical activity and smoking cessation in young patients with CAD. These healthier lifestyles changes should favor the BP target achievement and reduce the socioeconomic and clinical burden of premature CAD.