Treatment of primary CLL cells with bezafibrate and medroxyprogesterone acetate induces apoptosis and represses the pro-proliferative signal of CD40-ligand, in part through increased 15dDelta12,14,PGJ2.

B-cell chronic lymphocytic leukemia (CLL), the most common leukemia in older adults, remains largely incurable and novel treatments are urgently required. We previously reported powerful pro-apoptotic actions of bezafibrate (BEZ) and medroxyprogesterone acetate (MPA) against Burkitts lymphoma cells. Here, we demonstrate that BEZ and MPA individually, and more potently when combined (BEZ+MPA), induce apoptosis of unsorted and CD19(+ve)-selected CLL cells and abrogate the pro-proliferative activity of CD40(L). This action was tumor cell specific, as the drugs had little impact on normal donor cells. The antiproliferative actions of BEZ+MPA were associated with the generation of reactive oxygen species (ROS), and the proapoptotic actions were associated with the generation of both ROS and mitochondrial superoxide (MSO). BEZ increased prostaglandin D(2) (PGD(2)) synthesis by CLL cells, and treatment with PGD(2) and its antineoplastic derivative 15dDelta(12,14,)PGJ(2) recapitulated BEZ-induced antiproliferative and proapoptotic actions. The PGD(2) receptor antagonist, BW868C, did not block BEZ or PGD(2) activity against CLL cells. The potency of BEZ+MPA against CLL cells mirrored that of chlorambucil, and BEZ+MPA combined with chlorambucil was more potent than either treatment alone. Given the known safety profiles of BEZ and MPA, our data warrant further investigation of their potential as novel therapy for CLL.

Complications of the external (combination) rhinoplasty approach.

More rhinoplastic surgeons are using the external (combination) rhinoplasty approach for selected patients. Although several large series report few complications, the initial experience of newcomers may be different. A series of 26 external rhinoplasty approaches was examined, representing the initial experience of supervised residents. The most common complication was incising the anterior margin of the lower lateral cartilage at the juncture of the lateral and medial crura. To prevent this problem, it is recommended that the skin be elevated off the lower lateral cartilages from both a medial direction up over the domes and a lateral direction downward. To repair this complication, a figure-of-eight suture is used to reapproximate the incision.

The external (combination) rhinoplasty approach for the problem nose.

The external (combination) rhinoplasty approach has gradually gained acceptance as an approach to expose the nasal infrastructure. Its wide exposure has sharpened diagnostic skills by correlating pre-operative clinical impressions with specific anatomic deformities found at surgery. Its wide access has greatly increased as well as simplified the range of surgical maneuvers used in reconstruction. Following a review of the external approach, attention is focused on some of the problem nasal deformities where this approach has been helpful in obtaining good results. Nasal valve obstruction, nasal tip problems, nasal pyramid depression, and the crooked nose are discussed in terms of pathological anatomy and techniques of repair.

Autologous fascia grafts in head and neck plastic surgery.

Using an experimental animal model, we studied the stability of the size (gross morphology) and structure (histomorphology) of the fascia autograft. Fascia from a rabbit's leg was grafted in the subcutaneous tissue of the ear and abdomen and also into the intra-abdominal cavity. The weight and size of the autograft were recorded during the study period. Our findings showed that the size of the autograft remained stable, but there was a substantial weight reduction. Microscopic examination of histopathologic sections disclosed that there was no inflammatory response to the fascia. It also appeared to maintain its histomorphologic structure. Clinical trials with patients receiving facial plastic surgery are also reported. We believe a fascia autograft can be used to augment facial areas. We base this conclusion on the findings from previous reports, our animal experiment, and clinical trials.

Diverticular disease, carcinoma of the colon and diet in urban and rural Kenya Africans.

20 cases of diverticular disease and 12 cases of carcinoma of the colon have been demonstrated in 183 barium enemas in 1 year. These results, along with a dietary survey, show that diverticular disease can no longer be considered rare in Kenyan Africans and that a low-fibre diet is a contributory but perhaps not the only factor in its aetiology. There is probably an increasing incidence of diverticular disease as well as an increasing recognition of it. The incidence of carcinoma does not appear to be increasing to the same extent.

Transseptal, transsphenoidal hypophysectomy via the external rhinoplasty approach.

The external rhinoplastic method provides a rapid and convenient route for transseptal transsphenoid surgery of the pituitary gland. This procedure offers several practical advantages over the conventional subnasal approach and should be seriously considered by rhinologists active in this area.