Deficiency of a phosphatidylinositol-anchored cell adhesion molecule influences haemopoietic progenitor binding to marrow stroma in chronic myeloid leukaemia.

The interactions between haemopoietic progenitor cells and marrow stromal cells that are essential for the regulation of normal haemopoiesis are defective in chronic phase chronic myeloid leukaemia (CML). The presence of primitive progenitor cells (blast colony-forming cells, Bl-CFC) in the blood of patients with CML is reflected by their reduced capacity to bind to marrow derived stromal layers in vitro. Whereas normal bone marrow Bl-CFC bind irreversibly to cultured stromal layers (and none are found in normal blood), the Bl-CFC in CML bind transiently and then detach. The normal cell adhesion mechanism is partially sensitive to treatment with phosphatidylinositol-specific phospholipase C (Pl-PLC), indicating the participation of a phosphatidylinositol (Pl)-linked structure; however, when CML cells were treated with Pl-PLC it had no effect on progenitor binding. Two other Pl-linked structures, decay-accelerating factor (DAF) and lymphocyte function associated antigen-3 (LFA-3) were normally expressed on CD34 positive CML cells and normally susceptible to Pl-PLC treatment. The treatment of normal cells with Pl-PLC, to mimic the situation in CML, resulted in the indiscriminate and inefficient binding of Bl-CFC to stroma. Moreover, treatment of the normal cells with 5637 conditioned medium (CM), which contains haemopoietic growth factors, also reduced the binding capacity of normal Bl-CFC; 5637CM treatment did not alter the expression of DAF. It is proposed that a Pl-linked cell adhesion molecule (CAM) is deficient in CML as a consequence of the constitutive activation of ABL kinase whilst, in normal cells, CAMs attached in this manner are responsible for efficient adhesion to stroma and are regulated by growth factors.     

The role of individualized care in a service delivery system for children and adolescents with severely maladjusted behavior

Individualized care is a total system of care that is tailored to a child with severely maladjusted behavior. The services are unconditional, flexible, child and family focused, and interagency coordinated. The services follow the child until the child is adjusting in a normalized, mainstream environment. Individualized care is illustrated through two different projects. One is theAlaska Youth Initiative where individualized care was used to return children from out-of-state, residential programs. The other isProject Wraparound where it was used to prevent children from being removed from their families. This paper begins with the principles of individualized care and then describes the ecological, multilevel assessment process that coincides with the delivery of services. A case example from Project Wraparound is provided for clarification. Following the case example is a discussion of the need for evaluation data with some suggested strategies for documenting effectiveness. The final section focuses on two barriers to the implementation of individualized care. One is the tendency to think in terms of component programs rather than individualized services. The other barrier is the competition for scarce resources. Strategies are presented for overcoming both barriers.     

Antagonism of baclofen induced reduction in ventrobasal thalamic transmission by a TRH analogue

It has been shown previously that baclofen, the GABB beta receptor agonist, reduces the excitability of ventrobasal thalamic relay neurons measured by increases in latency and decreased discharge probability, while thyrotropin releasing hormone (TRH) analogues have the opposite effects. The present experiments have shown that the excitability reducing effects of baclofen on ventrobasal transmission are antagonised by the administration of TRH analogue CG3703. These results are discussed in the context of possible GABAergic and TRHergic modulation of VBT transmission from the thalamic reticular nucleus.     

Intracellular myocardial pH measured in vivo with sustained and reperfused coronary occlusion

Intracellular pH provides an important measure of the adequacy of local tissue perfusion. The purpose of this study was to measure regional intracellular myocardial pH (impH) in the ischemic zone in vivo during experimental canine coronary occlusion, with and without coronary reperfusion. Twenty adult dogs were studied. Ten dogs underwent permanent ligation of the proximal anterior left descending coronary artery (group L), five dogs had coronary reperfusion after 1 hour of total coronary occlusion (group R), and five dogs did not undergo ligation and served as controls (group C). Intracellular myocardial pH was measured by 31phosphorus nuclear magnetic resonance spectroscopy at baseline and then at 15-minute intervals for 6 hours after coronary occlusion (or after sham occlusion in group C). Baseline impH did not differ among groups (group C, 7.22 +/- 0.12 mean +/- standard error of mean; group L, 7.17 +/- 0.07; group R, 7.22 +/- 0.09). During hour 1 of total occlusion, the impH of both groups L (6.58 +/- 0.05) and R (6.55 +/- 0.08) was significantly reduced as compared with the impH of group C (7.3 +/- 0.12; p less than 0.05). At 0 to 1, 1 to 3, and 3 to 5 hours of reperfusion, the impH of group R (7.34 +/- 0.08, 7.27 +/- 0.07, and 7.29 +/- 0.06, respectively for these times) did not differ from group C (7.26 +/- 0.11, 7.21 +/- 0.07, and 7.25 +/- 0.10). At these same times, the impH of group L (6.47 +/- 0.05, 6.57 +/- 0.04, and 6.75 +/- 0.04) was significantly reduced as compared with both groups R and C (p less than 0.05). Thus a severe, persistent regional intracellular myocardial acidosis occurs in the ischemic zone with coronary occlusion but is rapidly corrected by reperfusion within 1 hour.     

A study of the selection and control of exercise casualties for hospital collective training

A project sponsored by HQ AMS TA and executed by an experienced TA Commanding Officer enhanced the effectiveness of Hospital Collective Training by improving the standard of selection and documentation of the input of exercise casualties, and set up the basis of a comprehensive library of casualty cards for future use.     

A quantitative study of normal locomotion in the rat

Three variables of locomotion; stride length, stride frequency and velocity have been measured in forty-eight rats. Median values were found to be 11.3 cm, 2.4 Hz and 24.2 cm/sec respectively. The results are assessed both as independent variables and in terms of their interaction. It was found that the two variables used to increase velocity (stride length and stride frequency) were not deployed equally during normal walking velocities (10-50 cm/sec). It is proposed that the study of these three readily quantifiable variables, particularly the relationships between velocity and stride frequency may be useful for the evaluation of locomotion in the assessment of neuropharmacologically active agents.     

Excretory urography with iohexol: evaluation in children

A multicenter clinical study was conducted using iohexol, a second-generation nonionic contrast medium, for excretory urography performed in 130 children. Doses of iohexol (300 mg iodine/ml) ranged between 150 and 660 mgI/kg (0.5 and 2.2 ml/kg). Iohexol was tolerated well, and no significant adverse reactions occurred. Sixty-five iohexol urograms were evaluated to determine the minimum dose for adequate visualization of the kidneys and collecting systems. A dose greater than 300 mgI/kg (1.0 ml/kg) always resulted in a urogram of diagnostic quality, while visualization was insufficient for diagnosis in 10% of studies done with doses of 150-300 mgI/kg (0.5-1.0 ml/kg). Another 65 iohexol urograms were compared in a blinded manner with a similar number of studies performed using iothalamate meglumine at comparable iodine concentration and dose. Visualization of calyces and pelvoinfundibular structures achieved with iohexol was rated better with statistical significance, but there was no difference in visualization of the renal parenchyma or ureters. Use of iohexol in excretory urography may be advantageous in children who are at greatest risk for an adverse reaction to contrast media or in those most likely to benefit from use of a low osmolality contrast agent.     

Hyperbaric oxygen in multiple sclerosis: a double blind trial

Eighty four patients with multiple sclerosis were treated in monoplace chambers with either hyperbaric oxygen at 2 atmospheres absolute or placebo. Comprehensive double blind assessment was carried out before, immediately after, and one month after treatment. There was no clinically important or significant benefit in any of the four major criteria of outcome--namely, the patient's subjective opinion, the examiner's opinion, the score on the Kurtzke disability status scale, or the time taken to walk 50 m. Out of 40 other clinical variables assessed, two (the sensory scale and timed writing with the left hand) showed a significant improvement without any subjective clinical correlate or change in any of seven other tests of left hand function. No group of symptoms was perceived by the patients as having improved more after treatment with hyperbaric oxygen than placebo. It is concluded that there is no basis for recommending hyperbaric oxygen in the treatment of multiple sclerosis.