Routine and specialised techniques in the diagnosis of haematological neoplasms.

The relative importance of traditional techniques used in the diagnosis of haematological neoplasms has altered during the past decade. Cytology and histology retain their central role but the importance of cytochemistry has declined, except in the diagnosis of AML. Immunophenotyping is of major importance in the diagnosis of ALL, some categories of AML and the LPDs. Cytogenetic and molecular genetic analysis are important in the diagnosis of CML and are becoming increasingly important in the diagnosis of chronic LPDs and other haematological neoplasms. Diagnostic haematology laboratories which are not specialist leukaemia centres should have ready access to all of these techniques to ensure optimal patient management. However, not all techniques need to be performed in every laboratory.     

Classification of normal and pathological tremors using a multidimensional electromagnetic system

A new multidimensional movement analysis system was used to record limb tremor over six degrees-of-freedom, and signal processing techniques were explored to develop a suitable classification method to distinguish between different types of tremor. The specific aims were to investigate the ability of the system to screen for differences between normal subjects and a group of neurological patients, and then to differentiate between three diagnostic groups of patients.

Postural tremor at the hand was recorded in normal subjects (n=24) and patients with essential tremor (n=21), multiple sclerosis (n=17) and parkinsonism (n=19). Data were collected using a 3Space Fastrak^® (Polhemus, Inc.) over six degrees-of-freedom (three translational directions and three rotations). Spectral estimates produced measures of tremor frequency and amplitude. Mathematical models of the data, using autoregressive modelling and K-nearest neighbour classification, produced parameters used to classify, (1) the normal subjects and 24 patients (using the three rotational movements), and (2) the three patient groups (using all six movement directions). Results were given in terms of the probability of each subject belonging to the groups being classified.

Tremor frequency and amplitude showed large overlap between the groups. The screening classification produced high probabilities of correctly classifying normal subjects (>70%) and patients (>70%). The diagnostic classification produced clear differences between the patient groups (60% for essential tremor, 80% for multiple sclerosis and 60% for parkinsonism).

The ability of this assessment technique to distinguish between postural tremor in normal subjects and neurological patients suggests that it could be developed as a screening tool. Classification of tremors between the patients groups, with a high degree of sensitivity, indicates the potential for further development of the system as a diagnostic aid.     

Thymocyte maturation is regulated by the activity of the helix-loop-helix protein, E47

The E2A proteins, E12 and E47, are required for progression through multiple developmental pathways, including early B and T lymphopoiesis. Here, we provide in vitro and in vivo evidence demonstrating that E47 activity regulates double-positive thymocyte maturation. In the absence of E47 activity, positive selection of both major histocompatibility complex (MHC) class I- and class II-restricted T cell receptors (TCRs) is perturbed. Additionally, development of CD8 lineage T cells in an MHC class I-restricted TCR transgenic background is sensitive to the dosage of E47. Mice deficient for E47 display an increase in production of mature CD4 and CD8 lineage T cells. Furthermore, ectopic expression of an E2A inhibitor helix-loop-helix protein, Id3, promotes the in vitro differentiation of an immature T cell line. These results demonstrate that E2A functions as a regulator of thymocyte positive selection.     

Internal suture for mallet finger fracture

An internal suture technique has been used for mallet finger fractures involving at least 30% of the articular surface. It provides fixation without a button or transfixion of the fragment. An independent retrospective review was conducted of ten patients at a mean follow-up of 17 months. Mean visual analogue score (0 to 10) for pain was 2.4 and satisfaction 7.9. Mean active range of motion was 13 to 49 degrees, passive motion was 2 to 56 degrees, pinch strength of effected finger to thumb was 3.8 kgf (81% of the opposite finger), grip strength 37.9 kgf (95% of the opposite hand). All fractures united and there were no neuromas. Complications included two nail deformities, a superficial infection and a pin track infection. One patient with a crush injury continued to have pain despite an arthrodesis.     

Hypochromic macrocytes: are they reticulocytes?

Automated full blood counters measuring the size and haemoglobin concentration of individual red cells by high and low angle light scatter can provide estimates of the percentage of cells which are abnormal in either or both of these variables. The hypothesis that an increase in the number of large cells with a reduced haemoglobin content ("hypochromic macrocytes") was indicative of a reticulocytosis was investigated. A correlation was shown between the percentage of hypochromic macrocytes and the reticulocyte count. This correlation was too weak to allow the actual reticulocyte percentage to be predicted from the percentage of hypochromic macrocytes. An increased percentage of hypochromic macrocytes, however, often indicates an increased reticulocyte count and thus serves to chart the haematologist to this possibility.     

The relationships among height,penile length,and foot size

To determine whether "folk myths" regarding the relationships of penile size to body height and foot size have any basis in fact, 63 normally virilized men were studied. Height and stretched penile length were measured; shoe size was recorded and converted to foot length. Penile length was found to be statistically related to both body height and foot length, but with weak correlation coefficients. Height and foot size would not serve as practical estimators of penis length.     

Assessing tremor severity.

A clinical rating scale which measured the severity of tremor in 20 patients (12 with essential tremor and 8 with "dystonic" tremor) was assessed at specific anatomical sites for both inter and intra-rater reliability using four raters. The scores obtained with the scale were compared with the results of upper limb accelerometry, an activity of daily living self-questionnaire and estimates of the tremor induced impairment in writing and drawing specimens. The results show that, for the purposes of routine assessment and therapeutic trials, a clinical rating scale can produce reliable results which are a more valid index of tremor induced disability than standard postural accelerometry.     

Ivermectin in human onchocerciasis: a clinical-pathological study of skin lesions before and three days after treatment.

Findings are presented from an histological study of 360 skin-snips (from iliac crests, calves, ankles) taken from 30 Ivory Coast onchocerciasis patients before and three days after an oral dose of ivermectin (200 micrograms/kg). This dose causes a nearly complete disappearance of the intralymphatic microfilariae and, surprisingly, of the "extra-vascular" ones. That shows the difficulty to localize the microfilariae on histological sections; these microfilariae are in fact inside the lymphatic pre-capillaries. There was no intensification of acute skin lesions after the treatment, thus showing that, contrary to diethylcarbamazine (DEC), ivermectin does not induce an exit of microfilariae into the extralymphatic connective tissue. Under the influence of ivermectin, paralyzed microfilariae may be carried passively towards the deep sub-cutaneous lymphatics, and then destroyed inside the regional lymph nodes, without producing major changes in the skin.     

Respiratory syncytial virus genotypes and disease severity among children in hospital

OBJECTIVES: To determine the spectrum of N and G genotypes of respiratory syncytial virus (RSV) causing respiratory tract infection and whether particular genotypes are associated with severity of infection. PATIENTS AND METHODS: Nasopharyngeal aspirates (NPAs) were obtained from 114 infants with acute respiratory tract infection due to RSV over two seasons. Viral mRNA was extracted from NPAs or cultured virus, reverse transcribed, and the cDNA amplified by the polymerase chain reaction using primers directed to parts of the N and G gene respectively. Amplicons were separately digested with four different restriction endonucleases for each gene. The fragments were separated by agarose gel, electrophoresis, and the electrophoretic patterns used to assign the various genotypes. Disease severity was assessed as very mild (upper respiratory tract signs only), mild (coryza and signs of lower respiratory tract infection), moderate (requiring nasogastric or intravenous fluids), and severe (requiring oxygen or ventilation). RESULTS: Five of the six known N genotypes were detected, but NP4 and NP2 were found most frequently. There was no association between N genotype and disease severity. Six G (SHL) genotypes were detected. Significantly (p = 0.04) more of the infants infected with the SHL2 genotype had severe or moderate disease. CONCLUSIONS: During the seasonal peaks of RSV respiratory tract infection at least 10 different RSV genotypes cocirculated. While there is no association between N genotypes and disease severity, infection with the SHL2 G genotype appears to result in moderate to severe disease.