Histologic changes mimicking biliary disease in liver biopsies with venous outflow impairment.

Impairment of venous outflow from the liver manifests as zone 3 sinusoidal dilatation and congestion (SDC) in liver biopsy. The spectrum of histologic changes in portal tracts has not been described. We studied liver biopsies from 34 patients with a confirmed diagnosis of venous outflow impairment (VOI). Liver transplant recipients and biopsies with cirrhosis and hepatic neoplasms were excluded. Clinical records were reviewed for laboratory tests and radiographic findings. In all, 19 patients had right heart disease, 13 had classic Budd-Chiari syndrome and two had veno-occlusive disease. Liver chemistry tests showed elevated liver transaminases (n=21; 61.8%), elevated alkaline phosphatase (n=31; 91.2%) and GGT (all 13 cases tested). The elevation in ALT and AST was mild (below 200 U/l in all cases), while alkaline phosphatase (ALP) was elevated above 500 U/l in nine (26.5%) patients and above 1000 U/l in three cases. On biopsy, all cases showed SDC. The portal tracts showed (a) portal expansion with bile ductular proliferation (n=16; 47.1%) accompanied by lymphoplasmacytic infiltrate (n=10), lymphocytic cholangitis (n=3) and portal or periportal fibrosis (n=11), (b) Portal and/or periportal fibrosis without ductular proliferation (n=3; 8.8%) or (c) Normal portal tracts (n=15; 44.1%). The combination of elevated ALP and bile ductular changes on biopsy suggested chronic bile duct disease. Ultrasound/CT scan evaluation of bile ducts in 26 patients showed no biliary tree abnormality. Antimitochondrial antibody testing in eight cases also yielded negative results. In conclusion, bile ductular proliferation, portal inflammation and portal-based fibrosis are commonly seen in liver biopsies of patients with VOI even in the absence of bile duct disease. These changes are often accompanied by elevated ALP and GGT and can lead to the suspicion of chronic biliary disease. In the absence of demonstrable abnormalities in the biliary tree, these changes can be attributed to venous outflow impairment.     

Insulin-like growth factor I promotes leiomyoma cell growth in vitro

Objective: Our purpose was to determine whether insulin-like growth factors I and II preferentially stimulate uterine leiomyoma cells versus myometrial cells in monolayer culture.Study design: Leiomyomas and normal myometrium were obtained at hysterectomy from five premenopausal women. Specimens were enzymatically digested for use in primary monolayer cell cultures. By use of serum-free media, insulin-like growth factor I or II was added in 1, 10, and 100 ng/ml concentrations to both cell types with the patient serving as her own control. Cell number, prolactin production, and proliferative index values were measured on day 15 of cell culture.Results: Significant increases in cell number were found in the leiomyoma cultures (p < 0.05) treated with 10 and 100 ng/ml insulin-like growth factors I but not with insulin-like growth factos II. Neither factor exerted a stimulatory effect on myometrial cells.Conclusion: Insulin-like growth factor sI preferentially stimulates leiomyoma cells in monolayer culture. These results suggest an autocrine-paracine role in vivo for this factor in conjuction with gonadal steroids in promoting leiomyoma growth.     

The Workup for Bariatric Surgery Does Not Require a Routine Upper Gastrointestinal Series

Background: Morbid obesity is a serious disease that afflicts over five million Americans, threatening their health with such co-morbidities as diabetes, arthritis, pulmonary failure and stroke. Surgery is the only effective therapy, providing long-term control of weight, diabetes, pulmonary failure, and hypertension for as long as 14 years. Because the operation presents a major expense, this study examined whether X-ray examination of the gut could be omitted safely as a cost-saving measure. Methods: The records of 814 consecutive morbidly obese patients who underwent gastric bypass were reviewed to determine: (1) whether these individuals had undergone an upper gastro-intestinal (GI) series, and (2) if these studies influenced therapy or caused cancellation or postponement of surgery. Results: Of the 814 patients, 657 (80.7%) underwent a preoperative GI radiography. Of these examinations, 393 (59.8%) were normal, with the following abnormalities in the remaining 264: hiatal hernia, 164; esophageal reflux, 39; Schatzki's ring, 18; small bowel diverticula, four; renal stones, four; malrotation, three; gall stones, two; pyloric ulcer, one; possible pelvic mass, one; calcified leiomyoma, one; and dysphagial lusoria, one. None of these findings resulted in cancellation or a delay in surgery. Conclusions: The upper GI series can be safely omitted from the routine preoperative evaluation of patients undergoing gastric bypass. At a cost of $741.00 per examination, this change represents significant potential savings. Similar evaluations of other routine preoperative tests may well provide a better basis for the evaluation of these complex patients.     

Accommodative hysteresis under static and dynamic stimulus conditions

The influence of continuous variation in dioptric demand on the accommodative hysteresis induced at near distances was examined in 14 visually-normal young adults. Tonic accommodation was measured before and after 10 minutes of sustained focus using a constant stimulus at 5 D, 6.5 D, and 8 D, as well as a stimulus which slowly and alternately increased and decreased over the continuous range from 5 D to 8 D. For approximately half the subjects, dioptric demand had to be very high (8 D) under static conditions to produce moderate but significant hysteresis, yet little or no attenuation of the effect occurred under the dynamic condition. For other subjects who consistently showed very large tonic changes (1.4 D or more) under static conditions, the hysteresis effect generated under dynamic conditions was greatly reduced (approximately 50 per cent) in magnitude. These findings suggest that the degree to which continuous variation in dioptric demand will disrupt the adaptive process may depend on individual differences in the rate and/or maximum level of tonic accommodative change. Such a relationship could have bearing on the particular strategy recommended for individuals who tend to experience blur at distance following nearwork.     

Novel therapeutic approaches for multiple myeloma

Summary: Multiple myeloma (MM) affects 15 000 new patients annually in the US, with 50 000 total patients, and remains incurable. Our preliminary in vitro and animal studies suggest a role for MM–host interactions in regulating MM cell growth, drug resistance, and migration in the bone marrow. Importantly, treatment strategies which target mechanisms whereby MM cells grow and survive in the bone marrow, including thalidomide and its potent immunomodulatory derivatives and proteasome inhibitor PS‐341, can overcome classical drug resistance in preclinical and early clinical studies.