Donald J. Glotzer

Tissue specific regulation of VEGF expression during bone development requires Cbfa1/Runx2

Vascular endothelial growth factor (VEGF) is a critical regulator of angiogenesis during development, but little is known about the factors that control its expression. We provide the first example of tissue specific loss of VEGF expression as a result of targeting a single gene, Cbfa1/Runx2. During endochondral bone formation, invasion of blood vessels into cartilage is associated with upregulation of VEGF in hypertrophic chondrocytes and increased expression of VEGF receptors in the perichondrium. This upregulation is lacking in Cbfa1 deficient mice, and cartilage angiogenesis does not occur. Finally, over-expression of Cbfa1 in fibroblasts induces an increase in their VEGF mRNA level and protein production by stimulating VEGF transcription. The results demonstrate that Cbfa1 is a necessary component of a tissue specific genetic program that regulates VEGF during endochondral bone formation.

The long-term outcome of restorative operation in Crohn's disease: influence of location, prognostic factors and surgical guidelines.

The course of all 113 patients with Crohns disease whose initial procedure involved an anastomosis operated upon from 1942 to 1972 was followed through 1980. The calculated cumulative 30-year total mortality was 23.4%, 16.7% disease-related. The cumulative recurrence rate was 29% at five years, 52% at ten years, 64% at 15 years and 84% at 25 years, with no important differences between disease locations and types of operation. Sex, age, duration, granulomas, enteral or perirectal fistulas and length of the resection, the disease, and the proximal resection margin had no significant influence on the rates of development of recurrent disease or on functional outcome. By far the most common site of recurrence was the neo-terminal ileum, but in ileocolitis compared with ileitis, recurrence was 5.2 times more likely (p = 0.0001) to involve the adjacent or remote colon as well. Moreover, only 1/63 ileitis patients eventually required ileostomy, whereas 15/47 patients with ileocolitis or colitis ultimately required this procedure (p less than 0.001). The current status of the patients was excellent or good in 64% and unwell or dead related in 24%. Urolithiasis developed in 19%.

TOXIC MEGACOLON IN ULCERATIVE COLITIS

A consecutive series of 18 patients with toxic megacolon has been managed with a policy of early operative intervention if optimal medical therapy has failed to effect a rapid remission. One patient achieved a sustained remission on medical management alone. Seventeen patients underwent ileostomy and colectomy. There was one death (5.6% mortality rate) in a complication of ulcerative colitis in which the average reported mortality rate has been 23.1%. It is suggested that surgical intervention be used early enough to prevent colonic perforation and the progressive metabolic deterioration that prolonged nonoperative medical management may produce. The ominous prognosis of toxic megacolon and of its surgical management in the past can be overcome by resort to earlier surgical intervention. Colectomy, rather than decompressive enterostomy, is advocated as the operative treatment of choice.

IMPAIRED SKIN AND HAIR FOLLICLE DEVELOPMENT IN RUNX2 DEFICIENT MICE

The transcription factor, Runx2, is known to play crucial roles in skeletal and tooth morphogenesis. Here we document that Runx2 has a regulatory role in skin and hair follicle development. The expression of Runx2 is restricted to hair follicles and is dynamic, pari passu with follicle development. Follicle maturation is delayed in the absence of Runx2 and overall skin and epidermal thickness of Runx2 null embryos is significantly reduced. The Runx2 null epidermis is hypoplastic, displaying reduced expression of Keratin 14, Keratin 1 and markers of proliferation. The expression pattern of Runx2 in the bulb epithelium of mature hair follicles is asymmetric and strikingly similar to that of Sonic hedgehog. This suggests that Runx2 may be a regulator of hedgehog signaling in skin as it is in bones and teeth. Supporting this possibility, we demonstrate that Sonic hedgehog, Patched1 and Gli1 transcripts are reduced in the skin of Runx2 null embryos. Moreover, we document Patched1 expression in epidermal basal cells and show that the skin of Sonic(+/-) embryos is thinner than that of wild-type littermates. These observations suggest that Runx2 and hedgehog signaling are involved in the well known, but unexplained, coupling of skin thickness to hair follicle development.

Villous adenoma of the duodenum

Abstract A case of villous adenoma of the duodenum is presented. These lesions are usually small and silent; when symptomatic, they are large, sessile, and easily detected radiologically. They are prone to spontaneous hemorrhage and malignant transformation. An early radiologic diagnosis and complete surgical extirpation of the lesion are frequently possible and may result in a favorable prognosis despite the ominous histologic appearance.

Preservation of continence after mucosal graft in the rectum and its feasibility in man.

Abstract 1. 1. An experimental operation in the dog in which rectal mucosa is replaced by mucosa of the upper part of the colon demonstrates that mucosal stripping and replacement do not destroy fecal continence and can be performed safely. 2. 2. The histories of two patients with chronic ulcerative colitis who had total abdominoperineal colectomy with rectal reconstruction are presented. The first operation failed because of technical factors but the second was successful.

Achalasia of the Esophagus Complicated by Varices and Massive Hemorrhage

MASSIVE and life-threatening hemorrhage from the esophagus was encountered in two patients with achalasia. Since bleeding of major clinical proportions has rarely been mentioned as a complication o...

Use of a reperfusion catheter after angioplasty dissection for salvage of ischemic renal allograft : case report

Percutaneous transluminal angioplasty was performed on a right common iliac artery stenosis presumed to be causing renovascular hypertension in a patient with a renal allograft anastomosis to the right external iliac artery. This was complicated by an obstructive dissection resulting in acute threatening renal allograft ischemia. Renal blood flow was restored by means of a transluminal reperfusion catheter until corrective surgery could be performed. This case is reported because such catheters can be acutely helpful to the interventionalist, and they have not been described in the radiology literature.

The Development of Current Surgical Treatment of Inflammatory Bowel Disease

The current state of the art of surgery for inflammatory bowel disease (IBD) is best understood if viewed from the perspective of its historical development. Through the years medical and surgical treatment have been intertwined and interdependent as physicians and surgeons have attempted to understand and treat these often devastating diseases. Since the pathogenesis of IBD remains unknown, current treatment still emphasizes “art.” Increasingly, however, scientific method has been used in exploring possible etiologies and in evaluating the results of various therapies including operation.

Chemical antroneurolysis with and without highly selective vagotomy

Abstract Because of the lower recurrence rate of ulceration when vagotomy is accompanied by antrectomy, we studied the effects of combining submucosal denervation of the antrum (antroneurolysis) with highly selective vagotomy (HSV). Chemical antroneurolysis (CANL) was performed by submucosal injection of 50% ethanol. In two gastric fistula dogs HSV produced a significant decrease in peak acid output (PAO) in response to 0.2 U/kg insulin (5.42 ± 0.46 → 3.32 ± 0.99 meq/15 min, P 0.92). CANL produced no change in maximum serum gastrin rise above basal in response to a test meal either in four pouch dogs (47.4 ± 2.54 → 40.9 ± 3.69 pg/ml, P > 0.13) or in four normal dogs (27.5 ± 3.41 → 33.8 ± 4.47 pg/ml, P > 0.16). Basal gastrins were also unchanged. In conclusion, we feel that CANL provides no significant advantage over HSV, while increasing its complexity.