Mechanical stimulation promotes osteogenic differentiation of human bone marrow stromal cells on 3-D partially demineralized bone scaffolds in vitro.

Bone is a dynamic tissue that is able to sense and adapt to mechanical stimuli by modulating its mass, geometry, and structure. Bone marrow stromal cells (BMSCs) are known to play an integral part in bone formation by providing an osteoprogenitor cell source capable of differentiating into mature osteoblasts in response to mechanical stresses. Characteristics of the in vivo bone environment including the three dimensional (3-D) lacunocanalicular structure and extracellular matrix composition have previously been shown to play major roles in influencing mechanotransduction processes within bone cells. To more accurately model this phenomenon in vitro, we cultured human BMSCs on 3-D, partially demineralized bone scaffolds in the presence of four-point bending loads within a novel bioreactor. The effect of mechanical loading and dexamethasone concentration on BMSC osteogenic differentiation and mineralized matrix production was studied for 8 and 16 days of culture. Mechanical stimulation after 16 days with 10 nM dexamethasone promoted osteogenic differentiation of BMSCs by significantly elevating alkaline phosphatase activity as well as alkaline phosphatase and osteopontin transcript levels over static controls. Mineralized matrix production also increased under these culture conditions. Dexamethasone concentration had a dramatic effect on the ability of mechanical stimulation to modulate these phenotypic and genotypic responses. These results provide increased insight into the role of mechanical stimulation on osteogenic differentiation of human BMSCs in vitro and may lead to improved strategies in bone tissue engineering.

Antiangiogenic therapy with somatostatin receptor-mediated in situ radiation.

Tumor growth and the development of metastases require an angiogenic response. Angiogenic vessels uniquely express somatostatin subtype 2 (sst 2) receptors that can transport somatostatin or its analogs into the cell. We hypothesized that radiolabeled somatostatin analogs could inhibit the angiogenic response by selectively destroying proliferating endothelial cells. We evaluated the antiangiogenic effects of 111In-pentetreotide, an sst 2-preferring somatostatin analog in a human vessel model. Disks of human placental vein were embedded in fibrin gels in culture and observed for angiogenic sprouting for 14 days. Vein disks were treated with 111In-pentetreotide (1.5, 15, and 150 microCi/mL) on the day of implantation. Control groups included disks treated with nutrient medium alone, with 111In-chloride, and with unlabeled pentetreotide. The percentage of wells that initiated an angiogenic response and the overall length and density of neovessel sprouts were assessed on Day 14. 111In-pentetreotide treatment did not completely block initiation of the angiogenic response but significantly decreased the growth of neovessels after initiation. Both the receptor-specific Auger electron-induced and nonspecific gamma radiation-mediated effects contributed to the angiotoxicity.

Clinical utility of frozen section in sentinel node biopsy in breast cancer.

One hundred sixty-five breast cancer patients underwent a sentinel lymph node biopsy procedure over a period of 2 years. Sentinel node (SN) could be successfully localized in 157 (95%) of the patients. Complete axillary lymph node dissection was performed only if the frozen section (FS) revealed a positive SN. All SN specimens were further evaluated by hematoxylin and eosin on multiple sections and cytokeratin immunohistochemisty. The patients whose SNs were negative by FS but positive by permanent histopathologic evaluation underwent a delayed axillary lymph node dissection. SN was positive in 41 of 157 (26%) patients. Eighteen (44%) of the 41 patients with SN metastases were diagnosed intraoperatively by FS and underwent a one-stage definitive surgical treatment. The benefit of FS was most notable in patients with T1c and larger lesions.

Paraganglioma of the bile duct.

We report the case of a 28-year-old woman with a 3-month history of right upper quadrant abdominal pain. Medical history and physical examination were unremarkable. Abdominal ultrasonography showed a dilated gallbladder, suggestive of gallstones, without bile duct dilatation. Serum chemistry values were normal. Laparoscopic cholecystectomy was planned, and a mass encircling the common bile duct was found. The procedure was converted to an open operation, and cholecystectomy, mass excision, and hepaticojejunostomy were done. The specimen was interpreted as paraganglioma of the bile duct. There were no manifestations of catecholamine hypersecretion or signs of biliary obstruction. Six years later, the patient is asymptomatic without signs of recurrence. This is the third report of paraganglioma of the hepatic ducts. We describe the clinical and pathologic findings and therapeutic approach in this unusual case and review the literature.

Is the quality of surgical residency applicants deteriorating?

BACKGROUND: Among directors of general surgery residencies, there is a concern that the quality of medical students applying to surgical residencies is declining. METHODS: Quality of surgical applicants was assessed by several methods including subjective opinions determined by survey and by objective data including student United States Medical Licensing Examination (USMLE) scores of matched candidates. The number of applicants interviewed, total interviews granted, proportion of Alpha Omega Alpha (AOA) students, and the rank order of the candidates matched was obtained by survey. The survey included data on postgraduate year 1 (PGY-1) residents from July 1996 to July 1999. Three mailings were made to 226 US surgical residency programs. RESULTS: Data were obtained from 90 programs. Surgery program directors disagreed with a survey statement that overall quality of applicants had declined (P <0.01), but agreed with a statement that activities of medical schools to enroll graduating students into primary care had hurt recruitment (P <0.001). Objective data revealed no change in mean USMLE part I scores of PGY-1 residents over the 4 years (P = 0.265, power = 0.81). There was no change in proportion of matched residents who were AOA over time. The mean score of all new PGY-1 residents, the rank of the first matched resident, the rank of the last ranked resident, and proportion of AOA students was higher in programs with five or more categorical spots when compared with programs of at most four (P <0.001). Across all programs, there was a trend to go lower on the rank list to fill categorical positions over time (P <0.001). CONCLUSIONS: There is a perception that medical school policies act to discourage recruitment of quality medical students into general surgery programs, and surgery programs are going deeper into their rank lists to fill categorical positions. However, the average USMLE part I score of applicants to surgical residencies and proportion of AOA applicants has not decreased.

Zinc, copper, and metallothionein metabolism after jejunoileal bypass surgery or small bowel resection in rats.

Liver dysfunction is a frequent complication of jejunoileal bypass (JIB) surgery, a procedure commonly used until recently to treat morbid obesity. It has been suggested that liver failure in JIB patients is due to bacterial overgrowth and translocation from the bypassed intestine. Because invading microorganisms cause hepatic inflammation these experiments evaluated zinc, copper, and metallothionein (MT) in two experimental rat models of intestinal surgery to determine whether their distribution in plasma and tissues was similar to the highly characteristic pattern observed during an inflammatory response. In the JIB rat model 90 per cent of the small intestine was isolated from the flow of digesta but remained viable in the abdominal cavity. In the small bowel resection (SBR) model 90 per cent of the small intestine was removed and the remaining intestine was resected. Data collected 21 days after surgery showed decreased growth rate and plasma zinc in the SBR and JIB rats that was significantly improved by supplemental zinc. All other measures of zinc, copper, and MT metabolism in the SBR rats were similar to those of controls. In JIB rats, however, liver copper, MT protein, and MT mRNA were significantly elevated, and a high proportion of the intracellular zinc and copper was associated with MT. The pattern of zinc, copper, and MT distribution in systemic circulation and liver of JIB rats suggests hepatic inflammation superimposed on low zinc and copper status. Lack of a similar response in the SBR rats confirms the involvement of the bypassed intestinal segment and supports the hypothesis that bacterial overgrowth and translocation are responsible for liver inflammation and dysfunction in JIB patients.

Brigadier General Theodore C Lyster [correction of Lister], MD: father of American aviation medicine.

Aviation medicine came into existence as a recognized entity when certain standards were established during and shortly after World War I. During this time, accident rates were high. In fact, a larger number of pilots were dying in accidents than in combat. Figures from Great Britain's casualty list at the close of the first year of World War I indicated that for every 100 aviators killed, 60 died as a result of some individual physical defect, 30 from some form of recklessness or careless behavior, 8 as a result of some mechanical defect in the airplane, and only 2 at the hands of the enemy. Aviators were found to be in poor physical condition. Because there were no established regulations with regard to workloads, aviators were frequently found to have been flying to a point beyond exhaustion. Because of workload, chronic fatigue, and emotional stress, aviators were constantly called upon to perform superhuman feats when not in peak physical condition. Errors in judgement were common. The majority of pilots lost weight as a somatic sign of stress. This was recognized by Theodore Lyster [corrected] who had recently been appointed as the Chief Surgeon, Aviation Section of the U.S. Army. Such problems were not diagnosed by medical officers because they were not trained to recognize them. Theodore Charles Lyster [corrected] was the son of Captain William J. and Martha Doughty Lyster [corrected]. He was an Army "brat" who entered the world on July 10, 1875. His childhood was spent in various posts around the country. At the age of 7, Lyster [corrected] contracted yellow fever while living in Fort Brown, TX. The boy was treated by William Gorgas, a young post surgeon. Gorgas was credited with the young boy's recovery. Later, Gorgas was to marry Lyster's [corrected] aunt making Lyster [corrected] his nephew by marriage. Having survived the yellow fever infection, young Lyster [corrected] had a lifelong immunity to the disease.

Infections within the peritoneal cavity: a historical perspective.

Physicians in antiquity dreaded abdominal infections. Despite the fact that peritonitis was extremely common, reports of successful surgical interventions were only anecdotal before the past century. Medicine's comprehension of the pathophysiology of the peritoneal cavity is still evolving. The history of our understanding of the process could be considered to be as recent as the current literature. Despite this, the mortality rates for patients with secondary peritonitis have fallen in the last century from almost 100 per cent to less than 10 per cent.