Liposomal 1,25 (OH)2 vitamin D3 compounds block proliferation and induce differentiation in myelomonocytic leukaemia cells

The vitamin D₃ derived hormone 1,25 (OH)₂ vitamin D₃ (1,25 D₃) is able to induce growth arrest and differentiation in myelomonocytic leukaemia cells. In order to allow for specific delivery to leukaemic cells the lipophilic compound was incorporated into the lipid membranes of liposomes. Liposomal 1,25 D₃ reduced proliferation as measured by ³H-thymidine incorporation in HL60 leukaemia cells by up to 60%. When liposomes were prepared at different concentrations of 1,25 D₃ 65% inhibition was achieved at 48 n M . The MC 1288 stereoisomer of 1,25 D₃ was more potent and had the same activity at 48 n M .
The effect of the liposomal compounds was specific to myeloid cells as they reduced proliferation in myelomonocytic HL60, monoblastic U937 and monocytic Mono Mac 6 cells but not in the T-cell lines Jurkat and Molt 4.
The antiproliferative effect of liposomal 1,25 D₃ was associated with an induction of differentiation since treated HL60 cells showed a monocytic morphology, increased expression of CD14 and decreased expression of CD33.
When peripheral blood leukaemic cells from M4 and M5 acute myeloid leukaemia (AML) patients were admixed with liposomal compounds an antiproliferative effect was seen in all five cases, including the two cases where free compounds led to enhanced growth. Liposomal delivery of 1,25 (OH)₂ vitamin D₃ may offer a novel approach to treatment of myelomonocytic leukaemia.     

Epicardial, Biatrial Synchronous Pacing for Prevention of Atrial Fibrillation after Cardiac Surgery

About 30% of patients develop AF after open heart surgery. Biatrial synchronous pacing (BSP) has been shown to promote sinus rhythm in patients with paroxysmal AF refractory to drug therapy. We conducted a prospective, randomized study to test the effect of BSP via epicardial electrodes on the incidence of AF after heart surgery, as compared to conventional therapy. To apply BSP, we attached two epicardial electrodes to the right and one to the left atrium. Immediately following surgery, BSP was initiated in the AAI-Mode at a rate of 10 beats/min above the underlying rhythm (maximum 110 beats/min) and continued for 3 days, during which the rhythm was continually monitored. After 21 (age 63 +/- 9 years) of the planned 200 patients, the study was prematurely aborted because of the proarrhythmic effect of BSP: 6 of the 12 patients treated with BSP developed sensing failure (P amplitude < 1 mV), which provoked AF in 5 of these 6 patients. BSP was discontinued due to diaphragmal stimulation in two patients and due to ventricular stimulation by a dislocated left atrial electrode in one patient. Two patients in the control group (n = 9) developed AF. Using the available standard technology, BSP via epicardial electrodes is not suitable to suppress AF after heart surgery, primarily due to postoperative deterioration of atrial sensing and its profibrillatory effect. In patients requiring atrial pacing after heart surgery, sensing thresholds must be closely monitored to prevent induction of AF.     

Maintenance of Remission in Ulcerative Colitis

PRD-y2 a well-absorbed mast cell stabilizer was examined in patients with ulcerative colitis by a double-blind controlled trial. Forty-three patients who were in clinical remission and taking sulfasalazine were randomly allocated to treatment with sulfasalazine or PRD-92 for six months. Relapses occurred in 42% of patients on PRD-92 and 24% on sulfasalazine. PRD-92 has a less prophylactic effect than sulfasalazine in ulcerative colitis.     

Determinants of Subsidiary Ventricular Pacemaker Suppression in Man

To investigate the relative contribution of the duration and rate of overdrive to subsidiary ventricular pacemaker suppression, in six patients with complete heart block after His-bundle ablation, ventricular overdrive stimulation studies were performed. The studies, which were spread over a mean follow-up period of 745 days, were carried out invasively with a temporary lead (one patient) as well as nonin-vasively with the implanted pacemakers and chest wall inhibition (five patients). The overdrive pacing rate was increased in steps of 10 beats/min, and the pacing duration was 15, 30, 60, 90, and 120 seconds at each level. A recovery period of 2 minutes was allowed after each overdrive stimulation. Incremental ventricular overdrive stimulation at increasing pacing durations consistently caused progressive suppression of ventricular impulse formation. Nonparamelric variance analysis demonstrated a significant (P < 0.0001) influence of both the pacing rate and duration on ventricular recovery time. Nonlinear regression showed an exponential increase in recovery time with incremental pacing rate and a biphasic increase in recovery time with incremental pacing duration. Beyond a pacing duration of 60 seconds ventricular impulse suppression was primarily dependent upon the pacing rate. A nonlinear regression model was applied to predict the number of heals required for return of the escape rhythm toward prepacing control values. The predicted maximum mean number of beats was 15.4 ± 5.9 and independent of the rate and duration of pacing, although, the initial temporary instability of the escape rhythm was directly related to the degree of overdrive.     

Exploring the Grief of Adolescents After the Death of a Parent

This study explored the grief of 26 adolescents after the death of a parent during the subjects' adolescent years. Data collection involved a one-time semi-structured interview. In addition, the adolescents were asked to write and draw about death. The study identified variables and themes that appeared to have possible significance for how adolescents coped. The study conclusions were that adolescents do grieve differently from children and differently from adults; younger adolescents even grieve differently from older adolescents. No discernible differences in grieving were ascertained on the basis of sex, type of death, or prior loss experiences. The one adolescent who was perceived as grieving in an adaptive manner had the advantage of open communication with family members, had closure with the parent now dead, had seen the parent when dead, and had been involved with the rituals surrounding the death. Implications for future research and recommendations for adults involved with adolescents are included.     

Body build and the desire for slenderness in young people

The median weight-for-height of young people in Brisbane are below the 'standard' values. In most groups the weight-for-height are symmetrically distributed, suggesting that this is the range of normal variation. Only among girls aged 15-19 years was there an excess of 'obese' subjects.
Almost all girls and young women say they want to lose weight, even though many are already well below the 'standard'. This trend is also present, but is less marked, among boys and young men. In these young people the desire for slenderness is causing unhappiness that seems out of proportion to the possible benefits of change. Health professionals should encourage a more balanced attitude to physiological variations in weight-for-height among young people.     

Isolation,identification, and characterization of a palladium complex in the catalytic deprotection of a protected peptide

The final catalytic deprotection in the large scale synthesis of thymopentin (Arg-Lys-Asp-Val-Tyr) produced an impurity which had not previously been observed. Isolation by preparative HPLC and spectroscopic characterization led to a postulated structure of the impurity as the 1: 1 thymopentin-palladium complex. A complex corresponding to the proposed structure was independently synthesized and shown to have identical chromatographic and spectroscopic properties with the isolated material. Proton and carbon (13) NMR were used to determine the coordination sites of the peptide with palladium. The susceptibility of the complex to hydrogenation indicated a possible source for its formation.