Recent developments in clinimetric instruments

Summary.  Assessment of impairment and function is essential in order to monitor joint status and evaluate therapeutic interventions in patients with haemophilia. The improvements in the treatment of haemophilia have required the development of more sensitive tools to detect the more minor dysfunctions that may now be apparent. This paper outlines some of the recent developments in this field. The Haemophilia Joint Health Score (HJHS) provides a systematic and robust measure of joint impairment. The MRI Scoring System has been designed to provide a comprehensive scoring system combining both progressive and additive scales. The Functional Independence Score for Haemophilia (FISH) has been developed to assess performance of functional activities and can be used in conjunction with the Haemophilia Activities List (HAL) which provides a self report measure of function. It is recommended that both measures are evaluated as these tools measure different constructs. Further refinement and testing of the psychometric properties of all of these tools is in progress. More widespread use of these tools will enable the sharing of data across the world so promoting best practice and ultimately enhancing patient care.     

PCR-positivity in harvested bone marrow predicts relapse after transplantation with autologous purged bone marrow in children in second remission of precursor B-cell acute leukaemia

Purging of autologous bone marrow (BM) grafts of children in second remission after a relapse of precursor B acute lymphoblastic leukaemia (ALL) in the BM has been carried out in our laboratory since 1987, initially by complement mediated cell lysis. This protocol was extended by performing an immunorosette depletion before lysis with complement. The aim of the present study was to assess by polymerase chain reaction the presence of residual leukaemic cells in the BM grafts before and after purging. The results were then correlated to clinical outcome. In 24/28 patients a PCR product was obtained by amplification of IgH and/or TcR junctional regions. BM before purging was available for analysis in 13 patients. We found that leukaemic cells could be detected in 8/13 (62%) of these grafts before purging . All these eight patients experienced a relapse, regardless of whether the purging procedure had been successful (defined as achievement of PCR-negativity) or not. In contrast, none of the five patients with PCR-negative grafts before purging relapsed ( P  = 0.0008). One patient died due to transplant-related toxicity. Of the remaining 23 patients, nine patients received a PCR-positive BM graft after purging. All these nine patients experienced a relapse as compared to 6/14 whose BM was PCR-negative after purging ( P  = 0.0072). Two of eight PCR-positive BM grafts could be purged to PCR-negativity. Thus, improvements both in treatment of leukaemia and in purging efficacy are still needed.     

Prevention and treatment of musculoskeletal disease in the haemophilia population: role of prophylaxis and synovectomy

Summary.  Prophylaxis is defined as primary (started before the onset of joint damage) or secondary (started after the onset of joint damage). The aim of primary prophylaxis is to prevent recurrent bleeding into joints and the development of chronic arthropathy in later life. When started early, and at most after two joint bleeds, the result is predictably excellent if there is compliance with the primary prophylaxis regimen. In order to decrease the need for central venous access devices to assure reliable venous access, a number of centres start primary prophylaxis with once weekly infusions with dose-escalation based on frequency of joint bleeding. A major unanswered question is whether primary prophylaxis can be safely discontinued in adolescents/young adults and if so, when. A promising predictor for the milder bleeding phenotype in persons with severe haemophilia is a later onset of joint bleeding. Once joint damage has occurred as a result of recurrent bleeding, secondary prophylaxis can only retard, but not prevent, ongoing joint damage. Other strategies to decrease recurrent bleeding from target joints include surgical synovectomy (ideally performed using an arthroscopic technique), radionuclide synovectomy and chemical synovectomy. These interventions have very good outcomes when performed by an experienced team. Given the very high cost of factor concentrates required for programmes of prophylaxis prospective studies that document benefits to the child and family, e.g. quality of life are to be encouraged.     

The spermatogenic cycle in the blue fox (Alopex lagopus): relative frequency and absolute duration of the different stages

The spermatogenic cycle of the blue fox was divided into eight distinct stages, based on an analysis of different cell associations of the seminiferous epithelium. The criteria used for classification of the stages were the type of spermatogonia, the occurrence of meiotic figures, and the shape and location of spermatids. The relative frequencies of the stages I to VIII were 25.7, 9.8, 8.7, 5.9, 13.8, 9.9, 10.6 and 15.5%, respectively. The duration of one cycle of the seminiferous epithelium was 12.0 +/- 0.2 days as determined from the progression of 5-bromo-2-deoxyuridine (BrdU)-labelled cells at various time intervals. The absolute duration of stages I to VIII was calculated to be 3.1, 1.2, 1.0, 0.6, 1.7, 1.2, 1.3 and 1.9 days, respectively. The estimated life span of primary spermatocytes was 19.2 days, of secondary spermatocytes less than 0.6 days, of spermatids with round nuclei 9.2 days and of spermatids with elongated nuclei 8.9 days.     

Muscle Water and Electrolytes in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis

ABSTRACT. Muscle water and electrolytes were determined in percutaneous muscle biopsy material from m. quadriceps femoris in 33 uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD) for 1–38 months, and in 34 normal subjects. The patients showed increased muscle contents of water, sodium, and chloride relative to fat-free solids (FFS); both intra- and extracellular water contents were increased. The total water content was inversely correlated with the duration of CAPD. The muscle potassium content was increased, both relative to FFS and to magnesium, whereas the intracellular potassium concentration was normal. Despite hypermagnesemia, the muscle content of magnesium was normal and the intracellular concentration was even slightly decreased due to the increase in intracellular water. We conclude that muscle water and electrolyte status is abnormal in CAPD patients, but the alterations appear to be less marked than in uremic patients undergoing other forms of therapy.     

Operative tumour yield obviates preoperative pancreatic tumour localization in multiple endocrine neoplasia type 1

Abstract. The efficiency of pancreatic tumour localization was prospectively evaluated in 12 consecutive patients with multiple endocrine neoplasia type 1 (MEN1), who were subjected to extirpation of 56 islet cell neoplasms of 0.2–4 cm in diameter (mean 0.8 cm) during pancreatic resection and enucleation. Computed tomography, angiography of the coeliac trunc and superior mesenteric artery, and percutaneous ultrasound correctly localized 7–12% of the tumours and 21–37% of the 19 lesions measuring at least one centimetre in diameter. Transhepatic portal vein sampling correctly located tumour sites in the proximal or distal portions of the pancreas in four out of six patients, but demonstrated unsatisfactory specificity. Intra-operative ultrasound and bidigital palpation of the pancreas had overall sensitivities of 86 and 45%, respectively, and eight lesions below 0.3 cm in diameter remained undetected with intraoperative ultrasound. It is concluded that diagnosis of endocrine pancreatic neoplasms is biochemical in MEN1 and that broad screening of tumour markers efficiently reveals pancreatic involvement decades before the development of a clinically overt disease. Intra-operative ultrasound is a requisite for pancreatic endocrine surgery in MEN1, and it obviates the need for conventional pancreatic imaging unless a pre-operative search for metastatic disease and anatomical aberrations is considered important.