Cost-effective multiplexing before capture allows screening of 25 000 clinically relevant SNPs in childhood acute lymphoblastic leukemia.

Genetic variants, including single-nucleotide polymorphisms (SNPs), are key determiners of interindividual differences in treatment efficacy and toxicity in childhood acute lymphoblastic leukemia (ALL). Although up to 13 chemotherapeutic agents are used in the treatment of this cancer, it remains a model disease for exploring the impact of genetic variation due to well-characterized cytogenetics, drug response pathways and precise monitoring of minimal residual disease. Here, we have selected clinically relevant genes and SNPs through literature screening, and on the basis of associations with key pathways, protein-protein interactions or downstream partners that have a role in drug disposition and treatment efficacy in childhood ALL. This allows exploration of pathways, where one of several genetic variants may lead to similar clinical phenotypes through related molecular mechanisms. We have designed a cost-effective, high-throughput capture assay of ∼25,000 clinically relevant SNPs, and demonstrated that multiple samples can be tagged and pooled before genome capture in targeted enrichment with a sufficient sequencing depth for genotyping. This multiplexed, targeted sequencing method allows exploration of the impact of pharmacogenetics on efficacy and toxicity in childhood ALL treatment, which will be of importance for personalized chemotherapy.

Transfer of hypercalcemia discriminant functions between local hospitals.

Transferability of discriminant functions is potentially useful both from an economical point of view and because, in general, medical knowledge, in this case discriminant functions, should be transferable. In the present study we have evaluated the transferability of discriminant functions, estimated from routine laboratory analysis, age and sex in two consecutively recorded populations with hypercalcemia including 162 and 257 patients with hypercalcemia. Discriminant functions were developed for each sex to distinguish between hypercalcemia associated with malignancy and hypercalcemia associated with other medical diseases. The total diagnostic accuracy in Herlev was 82 and 78%, in women and men, and increased to 87 and 86% in both sexes considering cases classified with posterior probability levels of 60%. In Hvidovre the total diagnostic accuracy was 81 and 84% in women and men, and increased to 83 and 89% at posterior probability levels higher than 60%. Transfer of the discrimination functions between the hospitals was followed by a decrease in diagnostic accuracy of 6-16%. At a posterior probability of 60% the diagnostic accuracies were 79% or more in the receiving hospital, in both sexes, except for men in Hvidovre. In relation to these results the concept of genuine and non-genuine transfer factors is introduced and discussed.

Within-centre evaluation of hypercalcaemia discriminant functions 5 years after their development.

Diagnostic hypercalcaemia discriminant functions, discriminating between clinically significant and non-significant hypercalcaemia, were tested 5 years after their development in order to evaluate the impact of time on their diagnostic capacity. Two populations, consisting of 257 and 129 patients with hypercalcaemia, were consecutively recorded, during six and three months respectively, 5 years apart under similar circumstances. The prevalence of hypercalcaemia was comparable in both populations, being 2.57 and 2.38% respectively (non-significant) (NS). The female/male ratio was 1.9 and 1.7 (NS). The discriminant functions correctly classified 81 and 80% of the women, respectively (NS) and respectively 75% and 64% of the men (NS) in the first and second recorded populations.

[Statistical study of workload at a birthing unit]. / Statistisk undersøgelse af arbejdsbelastningen på en fødegang.

The work consists of a statistical study of the workload on a labour ward. This included a study of the admission/birth frequency and an investigation of the factors that influenced the process of admissions and the time spent on the ward. Also the relation between the number of midwives and women in labour present on the ward was investigated. It was found that the variation in the number of spontaneous admissions/births could be described reasonably well by a Poisson distribution. A simple statistical model was proposed to calculate the number of midwives necessary at any given birth frequency. For a specific choice of parameters the model fitted the actual distribution very well. The relative frequency of complications was highest for women with no previous births and smallest for women with one previous birth. The time spent on the labour ward depended significantly on the number of times the woman had given birth before and on whether the present delivery was complicated.

Do local hospitals meet the analytical goals for the use of common reference intervals?

Blood samples were obtained from 183 blood donors and measured in two hospitals in the same geographical area using identical reference intervals and measuring equipment. The analytical bias of the clinical chemical analyses was investigated through paired measurements. The results showed that out of 15 routine analyses only four meet the goals for acceptance of common reference intervals, of which at least three were of clinical significance. The problems were reflected in the quality assessment results but, nevertheless, no action seems to have been taken.

[Spiral fracture of the humerus during arm wrestling]. / Spiralfraktur af humerus ved armlaegning.

The authors present the case of a body-builder who sustained a spiral fracture of the humerus during arm wrestling (Indian wrestling). The cause of the fracture and the underlying mechanism are discussed and it is concluded that it appears appropriate to warn body-builders and weight-lifters against arm wrestling.

Respective roles of 25 hydroxy-vitamin D, PTH, phosphate and renal function for the 1-alpha-hydroxylase activity in primary hyperparathyroidism.

Forty-three women (mean age 67 years, range 34-84 years) with primary hyperparathyroidism were investigated in an effort to examine the regulation of the 1-alpha-hydroxylase. This enzyme catalyzes the 1-hydroxylation of 25-hydroxy-vitamin D [25(OH)vit D] to 1,25-dihydroxy-vitamin D [1,25(OH)2vit D]. Serum 25(OH)vit D, 1,25(OH)2vit D, PTH, ionized calcium, phosphate and the 24-hour clearance of creatinine were measured. Different linear regression models were calculated with 1,25(OH)2vit D as the dependent variable. 25(OH)vit D was found to be definitely important for the regulation. The role of PTH for the 1,25(OH)2vit D production was discussed. Both renal function and phosphate concentration were found to influence the 1-alpha-hydroxylation.

[Supracondylar fracture of the femur following total knee replacement]. / Suprakondylaer femurfraktur efter total knaealloplastik.

A total of 157 cases of well-documented supracondylar fractures of the femur in patients with knee replacement on the ipsilateral side are reviewed. Predisposing factors and methods of treatment are described and a possible therapeutic model is presented.

[Spontaneous bilateral rupture of the extensor system of the knee in a patient with renal transplantation. Apropos of a case]. / Rupture spontanée bilatérale de l'appareil extenseur du genou chez un transplanté rénal. A propos d'un cas.

A case of bilateral spontaneous rupture of the extensor apparatus of the knee in a renal transplant recipient is reported. According to the literature the incidence of spontaneous ruptures is increasing, especially in uremic patients. The occurrence of such lesions should be borne in mind.

Fracture of the femur after knee arthroplasty.

The supracondylar fracture of the femur is a serious complication after total knee arthroplasty. We report our experience in the management of 16 patients with this complication and suggest that the main line of treatment should be conservative. Open reduction and plate fixation is precarious. In displaced fractures, however, the Rush pin technique was useful.

Popliteal aneurysm after plate osteosynthesis. A case report.

A false aneurysm of the popliteal artery caused acute ischemic symptoms 23 years after plate osteosynthesis of a distal femoral fracture. The protruding tip of a screw was found in the center of the aneurysmal sac.

Haemorrhagic compression of the femoral nerve complicating anticoagulation therapy. Case report.

Haemorrhagic compression of the femoral nerve is a rare complication of anticoagulation therapy. Two cases of femoral neuropathy secondary to such medication are presented and the literature is reviewed. The therapeutic approach to the problem is discussed.