Modulation of spontaneous B-cell differentiation in macroglobulinemia by retinoic acid

We previously showed that clonal blood B cells from patients with macroglobulinemia spontaneously differentiate in vitro to plasma cells. This process is dependent on an interleukin (IL)-6 autocrine pathway. We investigate here whether all-trans-retinoic acid (RA) interferes with B-cell differentiation either in patients with IgM gammapathy of undetermined significance (MGUS) or Waldenstrom's macroglobulinemia (WM). RA at a concentration of 10(-5) to 10(-8) mol/L inhibited by 50% to 80% the in vitro differentiation of purified B cells from four of five patients with MGUS and from one of five patients with WM as assessed by the IgM content of day 7 culture supernatants. We next determined whether this effect could be related to an inhibition of IL- 6 secretion by cultured B cells and/or a downregulation of the IL-6 receptor (IL-6R), which was constitutively expressed on patients' blood B cells. A 50% to 100% (mean, 80%) inhibition of IL-6 production was found in seven of 10 patients (five with MGUS and two with WM). The IL- 6R was no more detectable on cells from patients with MGUS after 2 days of treatment with RA and slightly downregulated in patients with WM. It was of interest that B cells susceptible to the action of RA belonged mostly to patients with IgM MGUS, which reinforces our previous data showing distinct requirements for IL-6-dependent differentiation of blood B cells from patients with VM or IgM MGUS.     

The plantaris tendon graft: An ultrasound study

To assess the value of ultrasound in imaging the plantaris tendon, ultrasounds were done on 26 legs in 25 patients who had a variety of surgical procedures on the posterior leg. Eighteen ultrasounds were done and interpreted before operation and eight after operation by a radiologist. The sonographic results were compared with the status of the plantaris as determined at surgery. The plantaris was present in 21 of 23 patients for a prevalence of 91%. Eighteen plantaris tendons were well visualized on ultrasound for a sensitivity of 86%. Of the three false-negative results, two occurred with thinned plantaris tendons that were less than 2 mm thick and hence considered inadequate for grafting. Therefore, the sensitivity for detecting a tendon suitable for grafting was 95%. All patients with positive studies had a plantaris tendon present for a specificity of 100%. A learning curve for the radiologist was demonstrated. Ultrasound appears to be effective in the preoperative imaging of the plantaris tendon.     

PCV19 Evaluation of The Costs of Heart Failure in Belgium

OBJECTIVE: To calculate the cost of heart failure in Belgium, based on an epidemiological model.
METHODS: We applied a state transition model to simulate the disease progression of heart failure over a period of 5 years, taking into account a weighted average of current practice. Costs related to current practice (1996 values) and disease progression were taken from the perspective of the health insurance. Unit costs of ambulatory care were collected through official listings; hospitalization costs for heart failure were collected from a database of 58 hospitals (ICD codes 402, 428, 429). Current practice was obtained through review of 250 patient records in primary care, starting on the day of initiating therapy up to 6 months later, and through expert interviews (2 rounds Delphi method).
RESULTS: The model indicates that the expected cost of treating heart failure in 1996 in Belgium was 318,000 Bef over 5 years, for an average number of life years of 3.59. ACE inhibitors are used in 34% of patients but are mostly applied only in higher NYHA classes (more ill patients), although studies recommend to prescribe those drugs earlier in the disease development, since they can avoid morbidity (hospitalisation) and morality. We calculated that starting earlier with ACE inhibitors and doubling their use would increase the total costs to 351,700 Bef for an extra survival time of 0.07 life years.
CONCLUSIONS: The study showed that state transition models can be applied in the assessment of the management of heart failure. Changes in the management should be expressed in extra costs per extra life year and compared to interventions in other disease areas.     

Visual pathways for object-oriented action and object recognition: functional anatomy with PET

The purpose of this study was to identify the functional anatomy of the mechanisms involved in visually guided prehension and in object recognition in humans. The cerebral blood flow of seven subjects was investigated by positron emission tomography. Three conditions were performed using the same set of stimuli. In the 'grasping' condition, subjects were instructed to accurately grasp the objects. In the 'matching' condition, subjects were requested to compare the shape of the presented object with that of the previous one. In the 'pointing' condition (control), subjects pointed towards the objects. The comparison between grasping and pointing showed a regional cerebral blood flow (rCBF) increase in the anterior part of the inferior parietal cortex and part of the posterior parietal cortex. The comparison between grasping and matching showed an rCBF increase in the cerebellum, the left frontal cortex around the central sulcus, the mesial frontal cortex and the left inferior parietal cortex. Finally, the comparison between matching and pointing showed an rCBF increase in the right temporal cortex and the right posterior parietal cortex. Thus object-oriented action and object recognition activate a common posterior parietal area, suggesting that some kind of within-object spatial analysis was processed by this area whatever the goal of the task.      

Rescue of implantation potential in embryos with poor prognosis by assisted zona hatching

The effect of the assisted zona hatching (AZH) procedure was investigated on 135 cycles with a poor prognosis of pregnancy due to: (i) maternal age > or = 38 years (45 cycles); (ii) three or more failed in-vitro fertilization (IVF) attempts (70 cycles), and (iii) patients possessing both inclusion criteria (20 cycles). The control groups (113 cycles) included patients possessing the same characteristics (42, 53 and 18 cycles respectively) and who did not undergo the AZH procedure. A total of 505 embryos was treated with AZH before transfer, resulting in: 14, 25 and 6 clinical pregnancies. The percentage of clinical pregnancies per cycle was significantly higher than controls for the first (31 vs 10% in control 1, P < 0.05) and second groups (36 vs 17% in control 2, P < 0.05). No significant difference in percentage of clinical pregnancies was found for the third group (30 vs 6%). Similarly, higher rates of implantation were obtained (11.5, 15 and 11%) compared to the respective controls (4%, P < 0.02; 6.3%, P < 0.01; and 1.5%). The rate of miscarriage in the AZH groups was similar to that obtained in the controls (22 vs 21%). Finally, the morphological analysis of the embryos transferred revealed that the poor prognosis condition is associated to a significantly slower rate of development and a higher rate of fragmentation. The present results indicate that AZH procedure improves pregnancy and implantation rates in patients with a poor prognosis of pregnancy by facilitating the hatching process in embryos which would otherwise be trapped inside the zona pellucida.      

Age at breast feeding start and postneonatal growth and survival

Colostrum has important anti-infective properties. It may also somehow promote the development of the child's immunological system. Discarding colostrum, as practised in some cultures, could thus have adverse health consequences beyond the neonatal period. To test this hypothesis, the age at breast feeding start of 734 healthy newborns in urban Guinea-Bissau was ascertained. The children were then prospectively followed up to 3 years of age. Eighty nine deaths occurred during the study. The probability of death in the age interval 28 days to 3 years was about 20%. The child's age at breast feeding start had no statistical impact on postneonatal growth or survival. As a single measure, early breast feeding start is not likely to make much difference for the long term growth or survival of children living under material poverty conditions.