Mixed hematopoietic chimerism following bone marrow transplantation for hematologic malignancies

Twenty-nine of 172 patients (17%) who received an allogeneic bone marrow transplant (BMT) from histocompatible sibling donors for hematologic malignancies were mixed hematopoietic chimeras; ie, they had a mixture of donor and host hematopoietic or lymphohematopoietic cells at greater than or equal to 14 days after transplantation. Twenty- four of the 29 mixed chimeras (83%) have remained in continuous complete remission for up to 116 months (greater than 9 years) following BMT. Four of the 29 patients (14%) have had recurrent leukemia, and 7 of the 29 (24%) have had moderate or severe graft-v- host disease (GVHD). Twelve of these 29 patients have persisted as stable mixed chimeras for greater than or equal to 2 years after BMT, whereas other patients converted to all donor-type hematopoiesis. The incidence of mixed chimerism was independent of the pretransplant regimen, the donor or recipient age (less than 20 v greater than 20 years), remission status (first complete remission of acute leukemia and first chronic phase of chronic myelocytic leukemia v later stages of disease), and type of leukemia. Our data indicate that mixed hematopoietic chimerism is not rare after BMT for hematologic malignancies and that its presence is compatible with long-term disease- free survival. Prospective studies of mixed chimerism after BMT are warranted to achieve better understanding of its biologic importance.     

Frequency and factors influencing portal hypertensive gastropathy and duodenopathy in cirrhotic portal hypertension

Portal hypertensive gastropathy and duodenopathy are distinct clinical and endoscopic entities. Data on factors influencing the development of these lesions are still emerging. Data on portal hypertensive duodenopathy are scarce. We prospectively studied 230 patients with liver cirrhosis and oesophageal varices attending the liver clinic of the Sanjay Gandhi Post Graduate Institute of Medical Sciences. One hundred and forty-two patients had no history of upper gastrointestinal bleeding, while the remainder had bled in the past. Endoscopic appearances were recorded before starting patients on a sclerotherapy programme. Forty-four patients were re-evaluated after variceal eradication. The frequency of portal hypertensive gastropathy (PHG) and duodenopathy (PHD) was 61 and 14%, respectively. Mild PHG was present in 85% and was severe in the rest. Portal hypertensive duodenopathy was mild in 50%, while in the other half it was severe. There was no relationship of PHG and PHD to: (i) a history of upper gastrointestinal bleed; (ii) size of oesophageal varices; (iii) aetiology of liver cirrhosis; or (iv) liver function status as assessed by Child Pugh's scores (P=NS for all). The prevalence of PHG was higher in those patients with oesophagogastric varices (74 of 107; 69%) compared with patients with oesophageal varices alone (68 of 123; 55%; P<0.05). However, no such increase in frequency of PHD was noted in patients with oesophagogastric varices. Sclerotherapy increased the frequency of PHG. Twenty-four patients had PHG before starting sclerotherapy, while it was noted in 33 patients 1–3 months after variceal eradication (P< 0.05). In contrast, there was no increase in the prevalence of portal hypertensive duodenopathy after sclerotherapy (P=NS). There was no correlation between endoscopic and histological changes of PHG and PHD. In conclusion, PHG is quite frequent in patients with cirrhosis and its frequency increases with the presence of oesophagogastric varices and after sclerotherapy. However, the frequency of PHD is low and is not affected by the factors studied.     

Use of highly polymorphic DNA probes for genotypic analysis following bone marrow transplantation

The use of DNA markers known as restriction fragment length polymorphisms is a sensitive and informative method of distinguishing patient and allogeneic donor cells after bone marrow transplantation. To apply the test, it is necessary in each case to find DNA probes that display patient-specific and donor-specific bands in Southern transfer hybridization. We have isolated a set of 12 cloned DNAs from highly polymorphic loci by which siblings can usually be distinguished. With just four of these probes, we can expect to distinguish the genotypes of the recipient and a sibling donor in more than 99% of cases (except between identical twins). The availability of many highly polymorphic probes also allows selection of an optimal probe for each case, one that can detect both the patient and donor-specific bands in a single hybridization with maximum resolution and sensitivity. We have applied these probes to the analysis of cells from peripheral blood and bone marrow after transplantation and demonstrated their usefulness in confirming engraftment of donor cells or graft rejection, and in detecting mixed lympho-hematopoietic chimerism.     

Posttransplant T-cell lymphoproliferative disorders--an aggressive, late complication of solid-organ transplantation

T-cell non-Hodgkin's lymphomas are an uncommon occurrence after solid- organ transplantation. We describe a morphologically and immunophenotypically distinct group of T-cell lymphoproliferative disorders that occurred late in the course of six patients with solid- organ transplants. The patients ranged in age from 31 to 56 years (median, 43). Three were male; all were splenectomized. The interval from transplant to the diagnosis of lymphoma ranged from 4 to 26 years (median, 15). Symptoms at presentation were related to sites of involvement. Pulmonary, marrow, and CNS involvement were present in five, four, and one case, respectively. No patient had lymphadenopathy. Five patients had an elevated lactate dehydrogenase level (range, 226 to 4,880 IU/L; median, 1,220 IU/L). Five of six patients had a leukoerythroblastic reaction. All cases had large-cell histology and frequently contained cytoplasmic granules. Those cases tested expressed CD2, CD3, and CD8 and were negative for B-cell antigens. T-cell receptor beta- and gamma-chain genes were clonally rearranged in three of three and one of three cases, respectively. All T-cell posttransplant lymphoproliferative disorders (T-PTLDs) studied were negative for Epstein-Barr virus (EBV), human T-cell leukemia/lymphoma virus type 1 (HTLV-1), human T-cell leukemia/lymphoma virus type 2 (HTLV-2), and human herpes virus type 8 (HHV-8) genomes. Treatment with acyclovir (three patients) or chemotherapy (three patients) resulted in two responses. All patients had an aggressive course, with a median survival duration of 5 weeks. In conclusion, a clinically aggressive T- PTLD may be a late complication of solid-organ transplantation and does not appear to be related to EBV, HTLV-1, HTLV-2, or HHV-8 infection.     

A randomised control trial of the effectiveness of personalised letters sent subsequent to school dental inspections in increasing registration in unregistered children

Background  

Recent studies have cast doubt on the effectiveness and efficiency of school based dental screening programmes in improving dental attendance or improving dental health. In 2002 the National Dental Inspection Programme was introduced in Scotland which categorises children by their dental health and informs parents of the findings via a personalised letter home and encourages dental registration. In addition, epidemiological data for local and national planning purposes is collected. This replaced an earlier school screening system in Lothian where a generic letter urging registration was sent to children who were identified as not being registered with a dentist. The objective of this study is to compare dental registrations rates among unregistered children in these two school inspection systems with a system where letters were sent home but no dental inspection was carried out.     

Trapezoid fracture caused by assault

In this report we describe an open fracture of trapezoid and break in anterior cortex of capitate due to assault in a young adult male. Direct impact force of a sharp object to the first web space caused the above fractures. Open reduction and internal fixation of the trapezoid was carried out using Kirschner wires. Cut extensor tendons, extensor retaniculum, capsule, adductor pollicis muscle, first dorsal interosseous muscle, soft tissue and overlying skin were sutured primarily. Three months after the operation the patient has made a complete recovery. There is no similar case reported in the literature.     

Twenty-Two-Year Follow-Up in the VA Cooperative Study of Coronary Artery Bypass Surgery for Stable Angina

We evaluated the 22-year results of initial coronary artery bypass surgery with saphenous vein grafts compared with initial medical therapy on survival, incidence of myocardial infarction, reoperation, and symptomatic status in 686 patients (average age 51) with stable angina in the Veterans Affairs Cooperative Study of Coronary Artery Bypass Surgery. Between 1972 and 1974, 354 patients were assigned to medical treatment and 332 to surgical revascularization. In the surgical cohort, 312 patients underwent operation (operative mortality 5.8%) and 25% subsequently underwent repeat operation (operative mortality 10.3%). In the medical cohort, 160 patients crossed over to surgery (operative mortality 4.4%) and 21% of these patients had reoperation (operative mortality 9.1%). Neither crossover nor reoperation was predictable by angiographic or clinical risk factors measured at baseline. The overall 22-year cumulative survival rates were 25% and 20% in the medical and surgical cohorts (p = 0.24). Corresponding rates in low-risk patients who had 1 or 2 vessels diseased, or 3 vessels diseased with normal left ventricular function were 31% and 24% (p = 0.024). Although significant at 10 years, there was also no long-term survival benefit for high-risk patients assigned to bypass surgery. The probabilities of remaining free of myocardial infarction and of being alive without infarction were significantly higher with initial medical therapy, 57% versus 41% (p = 0.02) and 18% versus 11% (p = 0.0031), respectively. This trial provides strong evidence that initial bypass surgery did not improve survival for low-risk patients, and that it did not reduce the overall risk of myocardial infarction. Although there was an early survival benefit with surgery in high-risk patients (up to a decade), long-term survival rates became comparable in both treatment groups. In total, there were twice as many bypass procedures performed in the group assigned to surgery without any long-term survival or symptomatic benefit.     

Comparison of growth rates of bovine retinal and brain microvascular pericytes in different oxygen concentrations in vitro

Background: The hyperoxic injury of the microcirculation in the central nervous system appears to be specific to the retina in premature mammals. Oxygen tensions in normal adult mammalian retina and brain vary between nearly 0 and 90 mmHg. This study sought to compare the in vitro replication of retinal and brain microvascular pericytes in normal glucose medium and in 1 %, 5% and 20% oxygen (equivalent to 15 mmHg, 35 mmHg and 150 mmHg, respectively).
Methods: A preliminary study, using oxygen micro-electrodes, confirmed that the pericellular oxygen tension of pericytes, cultured in medium under air, was within 13 mmHg of the tension of the gas phase above the media.
Pericytes were highly enriched by magnetic antibody cell sorting with the anti-pericyte monoclonal antibody (3G5) to 95% to 99% purity, to remove cell contaminants which may have invalidated the mitogenic assay.
Results: Mitogenic assays showed that brain pericytes replicated faster than their counterparts from retina (f< 0.0001, averaged for data from all culture conditions using three-way ANOVA). Reduction of oxygen tension from 150 to 15 mmHg led to significantly increased replication of retinal pericytes ( P =0.01), but an insignificant increase for brain pericytes.
Conclusions: We have found that pericytes from the brain and retina cultured conventionally in fetal calf serum consume a relatively low amount of oxygen. Decreasing the oxygen tension to 1% (15 to 20 mmHg) increased the replication of retinal pericytes but not brain pericytes in normal glucose concentrations and in fetal calf serum. That retinal pericyte replication is sensitive to variation in oxygen tensions, indicates that the retinal microvascular cells have a unique biological response. This growth sensitivity to oxygen may be important in the pathogenesis of retinopathy of prematurity.