Early gastric cancer and Helicobacter pylori: 34 years of experience at Charity Hospital in New Orleans

Good survival rates have been reported for resected early gastric adenocarcinoma (EGC) in patients found via screening procedures. However, the prevalence of Helicobacter pylori in EGC in unscreened populations is unclear. The major purpose of this investigation was to analyze the clinical experience and incidence of H. pylori in unscreened patients presenting with EGC at Charity Hospital over a 34-year period. From 1963 through 1997, the tumor registry at Charity Hospital compiled data on 2497 patients evaluated for gastric carcinoma. Of these patients, 26 (1%) had lesions that were confined to the mucosa or submucosa, i.e., T1N0M0 (American Joint Commission on Cancer classification). Pathology specimens and medical records were retrieved for confirmation of diagnosis and retrospective analysis for H. pylori. H. pylori was analyzed by Steiner staining and immunohistochemistry using a polyclonal antibody. EGC was detected in 12 men and 14 women with a mean age of 62 years. Upper gastrointestinal X-ray studies were performed on 19 of the 26 patients and failed to conclusively demonstrate a lesion in any case. Endoscopy was performed on 22 patients, and preoperative biopsies were positive in 95 per cent of these. Operative procedures included 2 local excisions and 22 subtotal and 2 total gastrectomies. No extended nodal dissections were performed. Microscopic evaluation revealed lesions limited to the mucosa in 63 per cent of cases and involving the submucosa in 37 per cent of the cases. Of the 14 patients evaluable of H. pylori, 79 per cent were positive for the bacterium. The status of 2 patients is unknown, and only 1 patient died of the original gastric cancer, for a disease-free survival of 96 per cent. The 5-year and 10-year overall survival rates were calculated to be 50 per cent and 21 per cent, respectively, when all causes of death were taken into consideration. Median follow-up of the survivors was 64 months. Resection of early gastric carcinoma in unscreened patients without extended lymphadenectomy yielded excellent results. H. pylori was present in 79 per cent of cases. These data suggest an association between H. pylori and EGC. Whether H. pylori infection is an etiologic factor in gastric cancer remains an area of active research.     

The HMG-CoA reductase inhibitor atorvastatin increases the fractional clearance rate of postprandial triglyceride-rich lipoproteins in miniature pigs

We have previously shown in vivo that the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor atorvastatin decreases hepatic apolipoprotein B (apoB) secretion into plasma. To test the hypothesis that atorvastatin modulates exogenous triglyceride-rich lipoprotein (TRL) metabolism in vivo, an oral fat load (2 g fat/kg body wt) containing retinol (50 000 IU) was given to 6 control miniature pigs and to 6 animals after 28 days of treatment with atorvastatin 3 mg. kg-1. d-1. A multicompartmental model was developed by use of SAAM II and kinetic analysis performed on the plasma retinyl palmitate (RP) data. Peak TRL (d<1.006 g/mL; Sf>20) triglyceride concentrations were decreased 29% by atorvastatin, and the time to achieve this peak was delayed (5.2 versus 2.3 hours; P<0.01). The TRL triglyceride 0- to 12-hour area under the curve was decreased by 24%. In contrast, atorvastatin treatment had no effect on peak TRL RP concentrations, time to peak, or its rate of appearance into plasma; however, the TRL RP 0- to 12-hour area under the curve was decreased by 20%. Analysis of the RP kinetic parameters revealed that the TRL fractional clearance rate was increased significantly, 1.4-fold (3.093 versus 2.276 pools/h; P=0.012), with atorvastatin treatment. The percent conversion of TRL RP from the rapid-turnover to the slow-turnover compartment was decreased by 47% with atorvastatin treatment. The TRL RP fractional clearance rate was negatively correlated with very low density lipoprotein apoB production rate measured in the fasting state (r=-0.49). Thus, although atorvastatin had no effect on intestinal TRL assembly and secretion, plasma TRL clearance was significantly increased, an effect that may relate to a decreased competition for removal processes by hepatic very low density lipoprotein.     

Factors influencing survival after gamma knife radiosurgery for patients with single and multiple brain metastases

BACKGROUND: Significant changes are restructurng the U.S. health care delivery system. National health reform is now extending itself into the public sector. Increased health and medical costs by federal and state governments are forcing a reevaluation of major entitlement programs, especially Medicaid. METHODS/RESULTS: Because Medicaid is the single largest item in many state budgets, states are now enrolling Medicaid patients into managed and coordinated care arrangements as a means to control costs and increase access to care. HMOs are not only competing for private patients but also actively seeking the Medicaid population. Nationally, almost one-fourth of all Medicaid patients are now enrolled in managed care plans. Various models and approaches have been developed by individual states. CONCLUSIONS: Because managed care enrollment in the Medicaid program has increased substantially in recent years, selected services including vision care are no longer rendered by any practitioner willing to accept Medicaid fees. Freedom of choice is now restricted to pre-selected and panel practitioners participating with the managed care program. The rules, regulations, billing procedures, fees, and program requisites will differ under managed care programs. Private optometric practitioners must consider entering economic and organizational relationships and linkages that make them attractive to managed care organizations.     

Differential sensitivity of human neuroblastoma cell lines to ethanol: correlations with their proliferative responses to mitogenic growth factors and expression of growth factor receptors

Early ethanol exposure depletes neurons in the developing nervous system, however the effects on neuronal precursors are not homogeneous. Some cells are more susceptible to ethanol toxicity than others. Growth factors are important mitogens for neuronal precursors. We tested the hypothesis that the differential sensitivity of neuronal precursors to ethanol is determined by their responses to growth factors using an in vitro model (SH-SY5Y, SK-N-SH, and IMR32 neuroblastoma cells) of neuronal precursors. The three cell lines were raised in a medium containing 10% or 0% fetal calf serum. Cells were exposed to ethanol and/or a growth factor. These factors included basic fibroblast growth factor, epidermal growth factor, insulin-like growth factor-I, nerve growth factor, and platelet-derived growth factors AA and BB. The numbers of cells per culture were counted both before and after 3 days of ethanol and/or growth factor treatment. In addition, the effect of ethanol exposure on the expression of receptors for these growth factors was examined. Neuroblastoma cells displayed differential sensitivity to ethanol. The growth of SH-SY5Y and SK-N-SH cells was inhibited by ethanol in a concentration-dependent manner. Ethanol did not affect cell viability. Thus, this inhibition resulted from a reduction of cell proliferation. In contrast, IMR32 cells were not affected by ethanol (even at concentrations as high as 800 mg/dl). The response to growth factors was also heterogeneous. In serum-supplemented medium, SH-SY5Y and SK-N-SH cells were stimulated by all of the tested growth factors. For cells raised in a serum-free medium, only the nerve growth factor was ineffective. IMR32 cells, however, were unaffected by most of these growth factors, regardless of the medium conditions. Ethanol blocked the action of all growth factors tested. In general, all cells expressed the specific receptors for the six growth factors. Only the expression of the basic fibroblast growth factor, insulin-like growth factor-I, and nerve growth factor receptors were reduced by ethanol exposure. In summary, neuroblastoma cells exhibit differential susceptibility to ethanol, and this correlates with their response to mitogenic growth factors. Some growth factors are a target of ethanol toxicity. These heterogeneous effects seem to parallel ethanol-induced changes of proliferating neuronal precursors in vivo.     

Methods to prepare RNA and to isolate developmentally regulated genes from Eimeria

Coccidians represent a large class of important intracellular parasites that traverse multiple developmental stages that are distinct and required to complete the life cycle. The biochemical details underlying the regulation of transformation from one developmental form to the next are limited and the study of such details presents unique obstacles. However, the genetic program is critical and may provide a basis for understanding the biology of these organisms in addition to the opportunity to suppress development and infection. We provide a basic overview of several strategies, including previously unpublished results, used by this laboratory to isolate stage-specific genes from Eimeria bovis. Additionally, we have included detailed discussions that summarize the associated advantages and disadvantages of each as applied to coccidia and potentially to other parasites in the phylum Apicomplexa. Given that the purification of sufficient quantities of high-quality RNA is vital, we have included detailed protocols for the isolation of RNA from various parasite stages. Also included is a detailed protocol to apply mRNA differential display to investigate stage-specific developmental regulation.