Experience of prophylaxis treatment in children with severe haemophilia

The practice of prophylactic treatment of boys with severe haemophilia has been evaluated in our centre. Prophylaxis was started at the median age of 3.7 years (range 0.4-12.7 years) in 38/41 children (93%) under 17 years of age. Median follow-up was 4.1 years (range 0.4-12.7 years). The criteria of primary prophylaxis according to the definition by the European Paediatric Network of Haemophilia Management was fulfilled by 9/38 (24%). Although a majority [76%, 29/38] of the children started prophylaxis after a median number of joint bleeds of 3.5, 70% of the children in this group had clinical joint scores of 0. Intravenous catheter insertion was required at a median age of 15.5 months (range 5-36 months) in 21% of the children, resulting in a catheter infection rate of 1.74 per 1000 catheter days. None developed an inhibitor on prophylaxis and three patients who had low-titre inhibitors (< 5 Bethesda units) prior to prophylaxis had undetectable inhibitors after prophylaxis. The home-treatment training programme required considerable time and cost. As a result, 87% of the children used peripheral venous access and hospital visits declined as prophylaxis became established. Parents' incentives for prophylaxis were that the children undertook many physical activities and sports previously not recommended, there was less parental anxiety and an overall improvement in the quality of life for the whole family.     

High Voltage Shock Induced Cellular Electrophysiological Effects: Transient Refractoriness and Bimodal Changes in Action Potential Duration

LI, H.G., et al .: High Voltage Shock Induced Cellular Electrophysiological Effects: Transient Refractoriness and Bimodal Changes in Action Potential Duration . The cellular electrophysiological effects of defibrillation shocks on the myocardium during ventricular fibrillation are not clear. The present study investigated the effects of high voltage shocks on membrane potentials of isolated guinea pig and pig papillary muscles during rapid activations simulating ventricular fibrillation. High voltage shocks induced an action potential with a prolonged duration, followed by a transient refractory state. Subsequent action potentials following this refractory state had shortened durations. The duration of the transient refractory state varied in proportion to shock intensity and stimulation rate, whether the shock was biphasic or monophasic. Shock induced prolonged depolarization was not a consistent finding and mainly observed with slow stimulation rates. In conclusion, high voltage shocks induce bimodal changes of the action potential duration associated with a transient refractory state during rapid activation. The rate dependency of this refractory state suggests that the duration of the shock induced refractory state may be longer in the fibrillating than the normal beating heart, and may contribute to successful defibrillation.     

Effect of the Peroxisome Proliferator, Ammonium Perfluorooctanoate (C8), on Hepatic Aromatase Activity in Adult Male CrI:CD BR (CD) Rats

The incidence of Leydig cell adenomas increases in CD rats fedfor 2 years with the hepatic peroxisome proliferator, ammoniumperfluorooctanoate (C8). Treatment with C8 increased the serumconcentration of estradiol in 2-week gavage studies, and feedingstudies at various time points up to 2 years, and was also accompaniedby increases in liver weight and hepatic ß-oxidationactivity. Since peroxisome proliferators induce both hepaticß-oxidation and specific cytochrome P450 enzymes,C8 may also induce aromatase (cytochrome P450-19A1), the cytochromeP450 mono oxygenase which converts androgens to estrogens. Thishypothesis was investigated in the present study. Adult maleCD rats were dosed daily by gavage for 14 days with 0, 0.2,2, 20, or 40 mg C8/kg body wt. An additional group, the pair-fedcontrol, was fed at a rate matched to the daily consumptionby the 40 mg C8/kg group. Treatment with C8 produced a dose-dependentdecrease in body weight, and increases in absolute and relativeliver weights, and in the protein yield of hepatic microsomes.These C8-induced changes were associated with a 2-fold increasein the serum concentration of estradiol and up to a 16-foldincrease in total hepatic aromatase activity. A significantlinear correlation was established between serum estradiol andtotal hepatic aromatase activity. The absolute weights and thearomatase activity of the testes were not affected by C8. Hepaticperoxisomal ß-oxidation activity and the microsomalconcentration of total cytochrome P450 were also increased byC8. A comparison of estimated EC50 values suggested that theseparameters may be less sensitive to induction by C8 than hepaticaromatase activity. Co-incubation of control liver microsomeswith C8 in the aromatase assay for 2 hr dose dependently reducedthe apparent aromatase activity. This inhibition of aromatasein vitro but increase in vivo was further investigated usingcultured rat hepatocytes. Decreases in aromatase activity werefound after up to 42 hr of treatment with C8, but the enzymeactivity was increased almost 2-fold after 66 hr. The resultsof this study suggest that the increased serum concentrationof estradiol produced by C8 in rats is at least partly due toa direct effect on the liver to increase synthesis of estradiolthrough induction of aromatase cytochrome P450 in the endoplasmicreticulum.     

Malposition of Transvenous Pacing Lead in the Left Ventricle

Malposition of pacemaker leads has been described in several locations but rarely in the left ventricle. The incidence and clinical course of this pacemaker complication are unknown. We describe clinical, electrocardiographic, chest X ray, and echocardiographic findings in four patients in whom the transvenous pacing lead was inadvertendy placed through the interatrial septum and mitral valve into the left ventricle, in these patients, lead misplacement was not recognized at the time of implantation and lead malposition was diagnosed a mean of 2 years later. All four patients had right bundle branch block configuration paced complexes. In retrospect, chest X rays suggested atypical lead position in all, but the initial posterioranterior and lateral chest X rays were misinterpreted and contributed to the delay in diagnosis. When lead misplacement in the left ventricle was considered it was confirmed by two-dimensional echocardiography. One patient subsequently presented with a stroke and the remainder were diagnosed when they presented with other unrelated problems. Pacing thresholds were normal at the time of implantation and behaved normally during follow-up. The patient presenting with stroke was anticoagulated and the other three have been managed expectantly without anticoagulafion. Diagnosis of left ventricular lead malposition is not difficult but requires a high index of suspicion. A 12-lead ECC and posterior-anterior and lateral chest X rays after implantation can be diagnostic. Patients with pacing lead in the left ventricle may remain asymptomatic with normal lead function during long-term follow-up. Anticoagulation should be considered when this problem comes to attention for the first time during follow-up.     

Comparative Functional Effects of Chronic Ventricular Demand and Atrial Synchronous Ventricular Inhibited Pacing

We compared the effects of chronic ventricular inhibited (VVI) and atrial synchronous ventricular inhibited (VDD) pacing on functional capacity in 8 patients with complete atrioventricular heart block. Permanent VDD (Medtronic #2409, ASVIP) pacemakers were implanted in four men and four women (age range 27-76 years, mean 58.9 +/- 18.4 years), and randomly assigned to a three-month period of VDD or VVI pacing in this single blinded, crossover study. Functional capacity was assessed by questionnaire, graded treadmill exercise testing and radionuclide angiocardiography prior to pacemaker implant and following each pacing period. Following 3 months of pacing in each of VVI and VDD pacing modes, maximum heart rate (83.4 +/- 14 vs 134.9 +/- 16.4 beats/min, p less than 0.001) and double product (147.5 +/- 58.3 vs 218.9 +/- 52.7, p less than .001) were greater with VDD pacing. Although exercise duration on treadmill exercise testing (5.3 +/- 2.9 vs 6.9 +/- 3.1 minutes, p less than 0.1) was greater in the VDD mode, the difference was not significant. Similarly, there was no significant difference in functional capacity as measured by questionnaire scores (50.1 +/- 8.4 vs 46.9 +/- 8.9, p less than 0.1) or in left ventricular ejection fraction for the two pacing modes (.54 vs .55, p less than .5). Only one patient reported a subjective improvement with physiologic (VDD) pacing, whereas the remaining patients stated no preference. We conclude that VDD pacing offers improved maximal cardiac work during exercise compared to VVI pacing.(ABSTRACT TRUNCATED AT 250 WORDS)     

PATTERN OF T-CELL RECEPTOR DELTA GENE REARRANGEMENT BY SOUTHERN BLOTTING AND POLYMERASE CHAIN REACTION TECHNIQUE IN HONG KONG CHINESE PATIENTS WITH NON-T-CELL HEMATOLOGICAL MALIGNANCIES

It has been recognized that clonal T-cell receptor delta (TCRδ) gene rearrangement is present in both T- and B-cell malignancies. The highly sensitive polymerase chain reaction (PCR) technique may be applicable to cases of leukemia and lymphoma of non-T-cell origin for detection of minimal residual disease (MRD). A PCR technique was used in this study to investigate the pattern of clonal TCRδ gene rearrangement in Hong Kong Chinese patients with non-T-cell hematological malignancies. Seventy-three patients with the diagnosis of acute leukemia and non-Hodgkin's lymphoma of non-T-cell origin were included in this study. There were 20 patients with common ALL (cALL), seven precursal B-cell ALL (PreB-ALL), 23 acute myeloid leukemia (AML), and 23 non-Hodgkin's lymphoma of B-lineage (B-NHL). Clonal rearrangement was detectable by Southern analysis using a Jδ1 probe in 41 per cent of ALL of B-lineage but in none of the B-NHL or AML. The samples were also studied further by monoclonal PCR amplification for TCRδ gene rearrangement. Three different sets of primers were employed to detect clonal rearrangement of the TCRδ gene. The Vδ1(D)Jδ1 recombination typically seen in T-cell malignancies were not seen in any of the of the non-T-cell malignancies. The Vδ2(D)Dδ3 recombination was found exclusively in ALL of B-lineage and was seen in 73 per cent of the Southern positive cases. Although clonal TCRδ gene rearrangement was undetectable by Southern analysis in our AML cases, 26 per cent had a Vδ2(D)Jδ1 recombination found by the PCR technique. Sensitivity of the PCR technique was determined by serial mixing and was up to 5–10 leukemic cells per 10⁴ nucleated cells. It was apparent from this study that it was feasible to detect clonal TCRδ gene rearrangement by the PCR technique in a proportion of the cases of non-T-cell hematological malignancies. The PCR technique can be applied to detect residual leukemic cells in marrow of patients in an apparent morphological complete remission. The value of this application requires further clinical evaluation and correlation.     

Abnormal clumsiness in children: a defect of motor programming?

Abnormal clumsiness in otherwise normal children has often been associated with both perceptual and motor defects, but the cause of this problem remains unclear. This study investigated the ability of clumsy children to programme movement and to use feedback, in both the visual and kinaesthetic modalities, for movement control. Clumsy and normal children performed simple and complex movements with vision either available, or precluded. The reaction time of the clumsy children was found to be longer than that of the normal children and the movement time for the complex, but not the simple response, was found to be longer for the clumsy group. These findings were interpreted as suggesting that clumsy children experience difficulty with the programming of movement and that, as a result, they depend more heavily on feedback for movement control than do normal children.     

A Quantitative Measurement of Spatial Orderin Ventricular Fibrillation

Quantifying Spatial Order in Fibrillation. Introduction: The degree of organization in ventricular fibrillation (V F) is not known. As an objective measurement of spatial order, spatial correlation functions and their characteristic lengths were estimated from epicardial electrograms of pigs in VF.
Methods and Results: VF was induced by premature stimulation in five pigs, EIectroj;raniswere simultaneously recorded with a 22 × 23 array of unipolar electrodes spaced 1.12 mmapart, Data were obtained by sampling the signals at 2000 Hz for 20 minutes immediately afterthe initiation of VF. Correlations between all pairs of signals were computed at various times.Correlation lengths were estimated from the decay of average correlation as a function of electrode separation. The correlation length of the VF in pigs was found to be approximately 4 to 10 mM. varying as fihrillation progressed. The degree of correlation decreased in the first 4 seconds after fibrillation then increased over the next minute.
Conclusion: The correlation length is much smaller than the scale of the heart, suggestingthat many independent regions of activity exist on the epicardium at any one time. On theother hand, the correlation length is 4 to 10 times the interelectrode spacing, indicating thatsome coherence is present. These results imply that the heart behaves during VF as a highdimensional, but not random, system involving many spatial degrees of freedom, which mayexplain the lack of convergence of fractal dimension estimates reported in the literature.Changes in the correlation length also suggest that VF reorganizes slightly in the first minuteafter an initial breakdown in structure.     

The Effect of Phase Separation on Biphasic Waveform Defibrillation

It has been hypothesized that the defibrillafion efficacy of a biphasic shock is caused hy the large change in voltage between the two phases. This study examined the effects of separating the two phases in time thus splifting in half the rapid voltage change at phase reversal. The study was performed in three parts each using six dogs. Part I determined defibrillation thresholds (DFTs) for two exponentially truncated biphasic waveforms (3.5/2 msec and 6/6 msec) with interphase time delays of 0, 1, 2, 3, 4, 6, 8, and 10 msec. In Part II, probability of success curves were generated using an up down method with 15 shocks for each delay for the 3.5/2 msec biphasic waveform with inferphase delays of 0, 2, 3, 4, and 5 msec. In Part III, DFTs were determined using a 3.5/2 msec and 6/6 msec biphasic as well as a fhird waveform that consisted of two sequential 6-msec pulses of the same polarity with interphase delays of 0, 5, 10, 15, 20, 25. 50, and 100 msec. In all three parts the defibrillating cathode was a 6.17 cm² transvenous spring electrode positioned in the RV apex and the anode was a 113 cm² cutaneous left chest wall eiectrode patch. With all waveforms, the trailing edge voitage of the first phase was equal to the negative of the leading edge voltage of the second phase. There was no statistical difference in DFTs or in 50% successful defibriliation points for phase separations from 0 to 6 msec and 0 to 5 msec for Parts I and II, respectively. In Part I there was a significant increase in DFTs for phase separations of 8 and 10 msec compared to a phase separation of 0 msec. In Part III there was no significant difference for seporations of 0 and 5 msec; however, there was a significant increase in DFT requirements for separations from 5 to 50 msec, which then decreased with a separation of 100 msec for ail three waveforms tested. In conciusion, defibriilation efficacy was unchanged with phase separations up to 6 msec. With phase separation, the rapid voltage change during phase reversal is split in half and. thus, cannot explain the improved efficacy of biphasic waveforms.