Unrelated donor marrow transplantation between 1977 and 1987 at four centers in the United Kingdom

Retrospectively we analyzed the histocompatibility data and clinical results of bone marrow transplantation in 51 patients who received marrow from unrelated donors (UD) from 1977 to 1987 at one of four UK BMT centers. We compared the results with those obtained in 51 transplants carried out at the same centers using HLA-identical (ID) sibling donors. Of the UD/recipient pairs 32 (63%) were serologically identical for HLA A, B, and DR antigens, and 37% showed varying degrees of mismatch. UD-BMT primary diagnoses were: severe aplastic anemia or Fanconi's anemia (n = 17), acute leukemia (n = 11), chronic myeloid leukemia (n = 21), and other conditions (n = 2). T cell depletion of the graft was associated with a significant improvement in survival in both UD and ID-BMT. Graft failure was more common in recipients of UD than of ID transplants (13 [25%] vs. 5 [10%] P = 0.05) but there was no significant difference in the frequency of acute or chronic graft-versus-host disease. Actuarial survival was superior for recipients of ID transplants (UD vs. ID: 49% vs. 78%, respectively, at 3 months; 32% vs. 63% at one year). Reduced survival for recipients of UD-BMT was confirmed in case control regression analysis (relative risk 3.0, P = 0.01). Nevertheless in patients whose only alternative is a partially mismatched family donor we think that UD-BMT is justified.     

Adipokines in cord blood and risk of wheezing disorders within the first two years of life

BACKGROUND: Adipokines are involved in the regulation of many inflammatory processes and are present at very high concentrations in cord blood of term infants. OBJECTIVE: We analysed data of a large prospective birth cohort study to examine whether adiponectin and leptin concentration in cord blood are determinants of wheezing disorders in children within the first 2 years of life. METHODS: Seven hundred and forty mothers and their newborns were included in this analysis. Adiponectin and leptin concentrations were measured in cord blood. The cumulative incidence of physician-reported asthma or obstructive bronchitis was recorded during a 2-year follow-up. RESULTS: During the first 2 years of life, asthma or obstructive bronchitis was reported by the caring paediatricians for 157 (19.6%) of the children. We found a strong interaction of cord blood adiponectin and history of atopic disease in the mother with respect to the risk of physician-reported asthma or obstructive bronchitis (P=0.006). Compared with children with cord blood levels in the middle quintile (reference category), the odds ratios for physician-reported asthma or obstructive bronchitis in the bottom quintile and top quintile were 0.14 [95% confidence interval (CI) 0.02-0.90] and 2.12 (95% CI 0.67-6.66), respectively (P for trend=0.0003), among children of mothers with a history of atopy. This association was independent of other established risk factors. Leptin levels in cord blood were not associated with risk of asthma or obstructive bronchitis. CONCLUSIONS: In children of mothers with a history of atopy, concentrations of adiponectin in cord blood could play an important role in determining risk of wheezing disorders in early childhood.     

Triquetral-lunate arthritis secondary to synostosis

Until recently the problem of painful, symptomatic arthritis of the wrist secondary to congenitally incomplete separation of carpal bones has been infrequently recognized. Five patients with either excessive stress loading or trauma had eight symptomatic wrists with congenitally incomplete separation of the triquetral-lunate joint. Three of these patients had bilateral symptoms. Six of the wrists had been treated by a limited wrist arthrodesis of the triquetral-lunate joint resulting in asymptomatic wrists and improved range of motion. It appears that patients with this congenital condition poorly tolerate stress loading or trauma secondary to deficient intra-articular cartilage formation resulting in a clinical and anatomic state similar to degenerative arthritis. We suggest a limited wrist arthrodesis as definitive treatment for symptomatic congenitally incomplete separation of the triquetral-lunate joint, with possible application in incomplete separation of the other intercarpal joints.     

Immunological and echocardiographic evaluation of decellularized versus cryopreserved allografts during the Ross operation.

OBJECTIVE: Compare the immunological and echocardiographic data of decellularized versus cryopreserved allografts used for RVOT reconstruction during Ross operation. METHODS: From 16/01/03 thru 07/10/03, 20 Ross operations were performed using decellularized (n=11) or cryopreserved (n=9) allografts. Echocardiography was done at discharge, 1, 3, 6 and 12 months and annually thereafter. Samples for determination of antibodies against HLA class I and II were obtained preoperatively and at days 5, 10, 30, 90 and 180 postoperatively. These samples were tested by the ELISA method in LAT-M dishes (unspecific) for identification of circulating antibodies and the results expressed as mean sample values (Is=DO/cutoff). If positive, LAT-E (specific) was performed and PRA levels determined. RESULTS: There was no mortality. Cryopreserved allografts showed marked Is values elevations for class I and II antibodies which started at the first month and remained elevated up to 6 months. In contrast, of the patients receiving decellularized allografts, seven remained negative, two patients had only marginal elevation of class I antibodies and two patients showed abnormal elevations of PRA levels. This response happened earlier than in the cryopreserved group, starting on the 5th postoperative day and has returned to baseline levels in one case. Echocardiography showed mild, but significant, elevation of gradients in cryopreserved valves but none in the decellularized. CONCLUSIONS: Decellularized allografts had normal function up to 18 months and showed important reduction of the immunogenic response when compared to cryopreserved valves.     

Effect of conjugated estrogens on platelet function and prostacyclin generation in CRF

In a double-blind, randomized, placebo-controlled cross-over study, we investigated in seven patients with chronic renal failure the effect of conjugated estrogens (0.6 mg/kg/day for 5 days) on template bleeding time and on thromboxane A2 (TxA2), beta-thromboglobulin (beta-TG) and prostacyclin (PGI2) concentrations in blood emerging from the template bleeding time incisions. Administration of conjugated estrogens resulted in a significant shortening of the bleeding time in six out of seven patients with a maximum effect 7 and/or 14 days following treatment. Both TxA2 (measured as thromboxane B2, TxB2) and beta-TG release in bleeding time blood were significantly higher following administration of conjugated estrogens as compared to placebo administration. No difference was seen in endothelial PGI2 (measured as 6-keto-prostaglandin F1 alpha) formation when patients were treated with conjugated estrogens as compared to placebo administration over the 28 day observation period. We conclude that in patients with chronic renal failure, infusion of conjugated estrogens results in a significant shortening of the bleeding time together with an increase in platelet reactivity, as indicated by an increase of TxA2 and beta-TG concentration in the microvasculature. No effect was seen on PGI2 production, thereby excluding a major effect on vascular prostaglandin metabolism.     

6-Hydroxydopamine treatment does not affect the young rat's ability to modify its response when changing from food to water deprivation

In this study we examined whether depletion of forebrain noradrenaline would affect latent learning as predicted on the basis of the role attributed to the dorsal noradrenergic bundle in attention. Either 6-hydroxydopamine (6-OHDA) or saline was injected into the lateral ventricles of male Wistar pups on postnatal day 12. Immediately after weaning the rats were food deprived and trained to choose the left arm of a Y-maze which contained food while the right arm provided access to water. Once they had learnt to enter the left arm they were allowed access to food but not to water for one day and then tested again. All the rats quickly adjusted their behavioural response to the fact that they were deprived of water. The 6-OHDA-treated rats' behaviour did not differ significantly from that of the controls.     

Morbidity among employees engaged in the manufacture or formulation of chlorpyrifos.

The prevalence of selected illnesses and symptoms during 1977-85 was compared between 175 employees potentially exposed to the organophosphate insecticide chlorpyrifos and 335 matched controls with no history of exposure to organophosphates. Subjects were subdivided into three exposure intensity groups on the basis of job title and air monitoring data for dose response testing. This classification scheme was shown roughly to correlate with plasma cholinesterase inhibition in the workers. No statistically significant differences in illness or prevalence of symptoms were observed between the exposed and unexposed groups or among the three exposure subgroups. Potentially exposed employees did report symptoms of dizziness and of malaise and fatigue relatively more often than subjects from the comparison group; however, further analyses by exposure level, process area, or time did not support a relation with exposure. No cases of peripheral neuropathy were seen among the exposed workers. Although the sample size was small and the statistical power limited, the cumulative exposures likely to have been experienced by this workforce exceed those to be expected for individuals using the product as recommended. The absence of exposure related adverse effects, including neurological impairment, is reassuring.