A sudden increase in factor VIII inhibitor development in multitransfused hemophilia A patients in The Netherlands. Dutch Hemophilia Study Group

The development of antibodies to factor VIII (inhibitors) in response to clotting-factor concentrates administration in hemophilia is common during the first few years of treatment but rare in multitransfused patients. We have investigated the possible association of a recently introduced factor VIII concentrate (Factor VIII CPS-P) in The Netherlands with the occurrence of inhibitors. To this effect, we conducted two studies. First, we performed a national multicenter study in which clinical information and inhibitor test results were obtained for 447 hemophilia A patients over the period 1988 through 1991. Secondly, for a baseline comparison we estimated the frequency of inhibitor development in a closely followed cohort of 144 patients, from 1984 through 1989. Before the introduction of Factor VIII CPS-P, the incidence of new inhibitors was 4.4/1,000 patient-years in the national study from March 1988 through May 1990, and 3.9/1,000 patient- years in the cohort followed from 1984 through 1989. These figures are similar to the incidence of new inhibitors that was found in a large cohort of patients in the United States followed in the 1970s. In the period that the new concentrate Factor VIII CPS-P was on the market, from June 1990 through November 1991, 11 clinically relevant inhibitors were detected, which yielded an incidence over this interval of 20.1/1,000 patient-years, a 4.5-fold increase compared with the previous interval (C195: 1.4 to 14.3). Nine of these 11 patients had in their lifetime received over 250 infusions with factor VIII preparations. whereas all of the inhibitors detected in the previous time interval, and all of the 24 inhibitor patients described in the US study, had received less than 250 infusions in their lifetime. All patients who developed inhibitors after June 1990 had been exposed to Factor VIII CPS-P, whereas only 75% of the patients who did not develop an inhibitor had been exposed to this product. In a prospective extension of the study, with a second inhibitor measurement after 3 months, we found that one additional inhibitor had developed during 52.5 patient-years of Factor VIII CPS-P use. In conclusion, there has been a sudden increase in the frequency of inhibitor patients, for a large part among multitransfused patients. It seems more than likely that this increase is associated with the introduction of a new factor VIII concentrate in The Netherlands.(ABSTRACT TRUNCATED AT 400 WORDS)     

Operational radiologic image archive on digital optical disks

A digital optical disk archive for storage of computed radiographic, computed tomographic, magnetic resonance, ultrasonographic, and digitized film radiographic images was installed. In the system, digital images enter a minicomputer, are temporarily stored on magnetic disks, and are archived onto write-once read-many optical disks at their full resolution. A pictorial index of minified images is maintained for each patient. After 8 months of operation, 49,400 megabytes of images had been retained on 19 optical disks stored, after January 1987, in a mechanical jukebox-style optical disk library. The success rate for archival capture of images during the initial period was 96.6%. The failures were due to overfilling of the magnetic disk, a problem addressed through the addition of a second magnetic disk unit. There were no medium-related image errors during the early period. Problems resulting from the slow speed of optical disk systems were addressed operationally by initiating recall of a patient's archived images from the optical to the faster magnetic disk as soon as the system received a request to acquire a new image. Also, optical disk retrieval times are expected to improve with technologic development.     

Vertebral bone density in children: effect of puberty

To determine changes in bone density during growth, trabecular vertebral density and an index of spinal cortical bone were measured with quantitative computed tomography in 101 children. The children were divided by age into three groups: prepubertal, indeterminate, and pubertal. Compared with prepubertal children, pubertal adolescents had significantly higher trabecular bone density and more compact bone in the spine (P less than .001). After controlling for puberty, vertebral bone density failed to correlate significantly with age, sex, weight, height, surface area, and body mass index. The results indicate that bone density increases markedly during puberty.     

Neuroplasticity and cellular resilience in bipolar disorder

Manji HK, Zhou R, Chen G. Neuroplasticity and cellular resilience in bipolar disorder. Bipolar Disord 2002: 4(Suppl. 1): 56–57. © Blackwell Munksgaard, 2002     

Non-invasive evaluation of sympathovagal balance in athletes by time and frequency domain analyses of heart rate and blood pressure variability

SUMMARY. We examined how the time and frequency domain measures of heart rate and blood pressure variability at supine rest reflect the sympathovagal balance of 23 female and male endurance athletes. Pharmacological blocking by atropine and propranolol was used as a standard for defining autonomic control of the heart. The Rosenblueth and Simeone model for neural control of heart rate was used to calculate the sympathovagal balance index (Abai)- Atropinization significantly decreased all time and frequency domain measures of heart rate and blood pressure variability. (3-Blockade significantly decreased further the low- < 0–07 Hz) and medium-frequency power (007-0-15 Hz) variability of R-R intervals (RRI) and SD of RRI. A_bal was 0–629 ± 0019, indicating that parasympathetic activity predominated in the athletes. Basal heart rate (r= 0–519, P < 001), SD of RRI (r= -0–533, P < 0–01), root-mean-square of successive RRIs (RRI RMSSD) (r= -0–579, P < -05), RRI total (r=-0–557, P <001) and RRI high-frequency (HF) power (r= -0–582, P < 0–01) correlated significantly with A_bal and parasympathetic activity index. We concluded that the best non-invasive method of evaluating the sympathovagal balance of athletes at supine rest is to measure SD of RRI, RRI RMSSD, HF and total power of RRI variability. All heart rate variability measures were mainly parasympathetically modulated. The nature of blood pressure variability measures remained unclear and they could not be used to evaluate the sympathovagal balance among athletes.