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Biomedical subjects

Sergio Huerta

Publications and source records attributed to Sergio Huerta.

10 recordsLinked to original sources
PubMed2003

Intestinal polyp formation in the Apcmin mouse: effects of levels of dietary calcium and altered vitamin D homeostasis.

This study evaluated the effects of various levels of dietary calcium on polyp formation, vitamin D homeostasis, and fecal bile acids in the Apcmin mouse. Female Apcmin mice were randomized to three groups and fed a purified diet with either half or double the level of calcium in control AIN-93G. Serum 25-OH-D and fecal bile acids were measured at weeks 0 and 12 of treatment. Mice were killed for polyp scoring by two observers blinded to treatment after 12 weeks. Results show there was no difference in polyp number or tumor load with dietary calcium in any treatment group. Serum 25-OH-D was reduced and total fecal bile acids were increased in animals that received the high calcium diet. We have previously shown that vitamin D supplementation diminishes polyp load; the lack of effect of an altered calcium diet seen here may be due to a disturbance in vitamin D homeostasis.

Animals↗
PubMed2003

Gene expression profile of metastatic colon cancer cells resistant to cisplatin-induced apoptosis.

The current chemotherapeutic modalities for advanced colorectal cancer are limited. DNA-platinating drugs such as cisplatin have poor efficacy against this malignancy. The aim of this study was to identify genes that render survival advantage after cisplatin treatment in metastatic colon cancer. Cell lines SW480 (primary colon cancer) and SW620 (metastatic lesion from the same patient) were obtained from ATCC. Apoptosis was measured by FACS analysis of cisplatin-treated (0.01-10 micro g/ml) and untreated cells. Simultaneous analysis of approximately 1200 cDNAs was performed by microarray technique on untreated and treated cells from lines. Microarray results were confirmed by RT-PCR. The SW620 cell line was more resistant to apoptosis induced by cisplatin. Western blot analysis revealed equal expression of pro-caspases 3, 8, and 9 in both cell lines. Microarray analysis identified 15 genes and 9 expressed sequence tags (ESTs) significantly altered both by cell type (metastatic vs. non-metastatic) and treatment vs. non-treatment. Several of these transcripts are well-characterized genes including MCT, GAD67, P19, GSTM3, Cyclin D1, ATM, and CO-029 that have been implicated in various malignancies. In the present study, we have identified a set of genes responsible for apoptosis resistance following treatment with cisplatin in the late stages of carcinogenesis. Targeting these genes may increase chemotherapy effectiveness in advanced colon cancer and reduce toxicity in normal tissue.

Adenocarcinoma↗
PubMed2002

PC-SPES inhibits colon cancer growth in vitro and in vivo.

PC-SPES is a mixture of eight herbs with antiproliferative activity in prostate cancer cell lines and antitumor effects in animal models of prostate cancer. In addition, evidence of clinical efficacy in advanced prostate cancer has been reported. PC-SPES has also been shown to have antitumor activity against several other cancer cell lines including breast and neuroepithelial cancer, melanoma, and leukemia cell lines. Because of these findings, we investigated the effects of PC-SPES in vitro in colon cancer cell lines SW480, SW620, and DLD-1 and in vivo in the Apc(min) mouse, a murine model for intestinal carcinogenesis. For the in vitro studies, colon cancer cell lines were exposed to an ethanolic extract of PC-SPES compared with a diluent control [ethanol < or = 0.3% (v/v)]. PC-SPES resulted in a marked suppression of cell proliferation in all colon cancer cells studied. PC-SPES (3 micro l/ml) caused a 95% inhibition of cell proliferation of the DLD-1 colon cancer cell line, and similar results were observed in the SW480 and SW620 colon cancer cell lines. Cell cycle analysis demonstrated a drastic (> or =60%) accumulation of cells in the G(2)-M phase with a concomitant decrease of cells in the G(0)-G(1) phase in all colon cancer cell lines studied after treatment with PC-SPES (1.5 micro l/ml for 48 h). Western blot analysis demonstrated a decrease in protein levels of beta-tubulin in the SW620 cell line exposed to PC-SPES. Terminal deoxynucleotidyl transferase-mediated nick end labeling analysis revealed an increase in apoptotic colon cancer cells incubated with PC-SPES. For the in vivo studies, female 4-5-week-old Apc(min) mice were randomized to two groups: a PC-SPES-treated group (n = 11) received 250 mg/kg/day (0.2 ml) PC-SPES via gastrointestinal gavage; and a control group (n = 10) received 0.2 ml of the vehicle solution (1.5% carboxymethylcellulose with 0.2% Tween 20) via gastrointestinal gavage. Both groups were treated five times a week for 10 weeks. After treatment, the gastrointestinal tract was dissected for polyp scoring by two observers blinded to treatment. The Apc(min) mice given PC-SPES had a 58% reduction in tumor number and a 56% decrease in tumor load. No effect on either food intake or body weight was observed in the treated versus sham groups. The present study is the first to report the potent activity of PC-SPES against colon cancer. Both cell cycle arrest and apoptosis occurred after treatment with PC-SPES. This suggests that the components of this herbal mixture, either independently or in combination, acted in colon cancer, resulting in a drastic effect on tumor initiation and tumor progression.

Animals↗
PubMed2002

1alpha,25-(OH)(2)-D(3) and its synthetic analogue decrease tumor load in the Apc(min) Mouse.

Both calcium and vitamin D are thought to be able to inhibit colon carcinogenesis. To better define the effects of vitamin D, we studied 1alpha,25-(OH)(2)-D(3) and a noncalcemic synthetic analogue of vitamin D(3) (VD(3)) in the Apc(min) mouse. Female Apc(min) mice 4-5 weeks old were randomized to four groups: a VD(3)-treated group (n = 11) were given injections of 0.01 microg of 1alpha,25-(OH)(2)-D(3) i.p. three times per week; an analogue-treated group (n = 10) received 5 microg of 1alpha,25-(OH)(2)-16-ene-19-nor-24-oxo-D(3) i.p. three times per week; and a control group (n = 12) received sham injections of PBS. A sulindac-treated group (n = 10) was used as a positive control. Doses of these compounds were chosen based on previous toxicity studies in mice and rats. After 10 weeks of treatment, mice were killed and two observers (S. H., R. W. I.), blinded to treatment, scored polyp number and size. Tumor number was not affected with 1alpha,25-(OH)(2)-D(3) or vitamin D analogue administration. A significant decrease in total tumor load (sum of all polyp areas) over the entire gastrointestinal tract was seen in the analogue (36% decrease; P < 0.05) and the VD(3) groups (46%; P < 0.001). There was a significant decrease in polyp number (49%; P < 0.001) and polyp area (70%; P < 0.001) in the sulindac group. Reverse transcription-PCR of the total RNA derived from intestinal tissue revealed expression of the vitamin D receptor throughout the small intestine and the colon. Serum calcium levels in the analogue group were not elevated at week 4 of treatment and only moderately elevated (22%) by week 8 (P < or =0.001). In contrast, serum calcium in the VD(3) group was significantly elevated (P < or =0.001) at weeks 4 (23%) and 8 (45%). Food intake and growth rate were significantly lower in the VD(3) group (26%, P < 0.001, and 27%, P < 0.001, respectively) at week 10. In contrast, food intake and growth rate were similar for the control, sulindac, and analogue groups. Our results indicate that a noncalcemic analogue of vitamin D can significantly decrease intestinal tumor load in Apc(min) mice without severe toxic side effects and suggest that these compounds may have utility as chemopreventive agents in groups at high-risk for colon cancer.

Adenomatous Polyposis Coli↗
PubMed2002

Assessment of routine elimination of postoperative nasogastric decompression after Roux-en-Y gastric bypass.

BACKGROUND: Anastomotic disruption after surgical intervention is an infrequent complication, but may lead to severe morbidity and mortality when it occurs. Of the various gastric procedures, the Roux-en-Y gastric bypass (RYGB) has one of the highest risks for anastomotic leakage. Consequently, a nasogastric tube (NGT) is frequently placed when these operations are performed. Most studies examining the outcomes for patients without postoperative NGTs have been relatively small with groups of patients undergoing a variety of operations. Assessing the incidence of anastomotic leaks by routine elimination of postoperative NGTs requires a large number of patients. In this study, we assessed the safety and efficacy of routine elimination of NGTs in a large cohort of patients undergoing a single operation. METHODS: We reviewed our experience with 1067 patients who underwent RYGB at the UCLA medical center. Fifty-six patients had NGTs routinely placed before the implementation of a standard protocol, which eliminated postoperative NGT decompression. The complication rate for the RYGB patient cohort with and without postoperative NGT was compared. RESULTS: We found no difference in the complication rates between the 2 groups (Fisher exact test; P =.21). CONCLUSIONS: Our findings suggest that routine placement of an NGT after RYGB is unnecessary.

Adult↗
PubMed2002

Vitamin A deficiency in a newborn resulting from maternal hypovitaminosis A after biliopancreatic diversion for the treatment of morbid obesity.

BACKGROUND: Biliopancreatic diversion (BPD) has been advocated for the treatment of morbid obesity. This procedure has the theoretical advantage that patients retain normal eating capacity and lose weight irrespective of their eating habits. However, vitamin deficiencies may develop because BPD causes malabsorption. OBJECTIVE: This report describes a 40-y-old mother and her newborn infant, who developed vitamin A deficiency as a result of iatrogenic maternal malabsorption after BPD. Our primary objective is to show that BPD patients need close follow-up and lifelong micronutrient supplementation to prevent nutrient deficiencies in themselves and their offspring. DESIGN: The medical records of the mother and infant were reviewed, and their clinical course was followed until 10 mo postpartum. The mother was also interviewed on several occasions about her medical care, follow-up, and supplemental vitamin use. RESULTS: The mother developed night blindness with undetectable serum vitamin A concentrations in the third trimester of her pregnancy. Her vitamin A deficiency was untreated until she delivered her infant. At delivery, the infant also had vitamin A deficiency. He may have permanent retinal damage, but this is still unclear because the ophthalmologic examination performed at 2 mo of age was inconclusive. CONCLUSIONS: Complications of BPD may take many years to develop, and the signs and symptoms may be subtle. Because of the malabsorption that results from BPD, patients need lifelong follow-up and appropriate vitamin supplementation to prevent deficiencies. These nutrient deficiencies can also affect the offspring of female BPD patients.

Adult↗
PubMed2002

Male gender is a predictor of morbidity and age a predictor of mortality for patients undergoing gastric bypass surgery.

PURPOSE: To determine preoperative risk factors predictive of adverse outcomes after gastric bypass surgery. SUMMARY BACKGROUND DATA: Gastric bypass results in sustained weight loss for seriously obese patients, but perioperative complications can be formidable. Preoperative risk assessment is important to establish the risk-benefit ratio for patients undergoing these operations. METHODS: Data for 10 risk factors predictive of adverse outcomes were collected on 1,067 consecutive patients undergoing gastric bypass surgery at the UCLA Medical Center from December 1993 until June 2000. Univariate analyses were performed for individual risk factors to determine their potential significance as predictors for complications. All 10 risk factors were entered into a logistic regression model to determine their significance as predictors for complications. Sensitivity analysis was performed. RESULTS: Univariate analysis revealed that male gender and weight were predictive of severe life-threatening adverse outcomes. Multistep logistic regression yielded only male gender as a risk factor. Male patients were heavier than female patients on entry to the study, accounting for weight as a potential risk factor. Patients older than 55 years had a threefold higher mortality from surgery than younger patients, although the complication rate, 5.8%, was the same in both groups. Sensitivity analysis demonstrated that the risk for severe life-threatening adverse outcomes in women increased from 4% for a 200-lb female patient to 7.5% for a 600-lb patient. The risk increased from 7% for a 200-lb male patient to 13% for a 600-lb patient. CONCLUSIONS: Large male patients are at greater risk for severe life-threatening complications than smaller and/or female patients. Risk factors thought to be predictive of adverse outcomes, such as a history of smoking or diabetes, proved not to be significant in this analysis. Older patients had the same complication rate but a threefold higher mortality, suggesting that they lack the reserve to recover from complications when they occur.

Adult↗
PubMed2002

Management of gastrojejunal anastomotic leaks after Roux-en-Y gastric bypass.

Anastomotic leaks after Roux-en-Y gastric bypass (RYGB) potentially result in considerable morbidity and mortality. In the present report we describe our experience with the management of gastrojejunal anastomotic leaks. Tachycardia and fever are considered early signs of anastomotic disruption. Patients weighing less than 350 pounds underwent radiographic testing to diagnose gastrojejunal disruption. Those with severe leaks or patients too large for radiographic evaluation underwent exploratory laparotomy. For severe anastomotic disruptions a retrograde transanastomotic jejunal sump drain was placed. Twenty-four (1.3%) anastomotic leaks occurred in 1789 RYGBs. Five of the leaks were classified as severe and required retrograde sump tube placement. There was one mortality and all of the other patients completely recovered. Aggressive and early intervention for anastomotic disruption after RYGB is necessary to ensure the best possible outcomes for patients with this complication. A high index of suspicion for leaks in postoperative RYGB patients with tachycardia is required if patients are to have good outcomes when complications develop.

Adult↗
PubMedDate not supplied

Safety and efficacy of postoperative continuous positive airway pressure to prevent pulmonary complications after Roux-en-Y gastric bypass.

Continuous positive airway pressure (CPAP) is used to prevent apneic arrest and/or hypoxia in patients suffering from obstructive sleep apnea. This modality has not been universally accepted for patients following upper gastrointestinal surgery because of concerns that pressurized air will inflate the stomach and proximal intestine, resulting in anastomotic disruption. This study was performed to assess the safety and efficacy of postoperative CPAP for patients undergoing a gastrojejunostomy as part of a Roux-en-Y gastric bypass (RYGB) procedure. A total of 1067 patients (837 women [78%] and 230 men [22%]) were prospectively evaluated for the risk of developing anastomotic leaks and pulmonary complications after the RYGB procedure. Of the 1067 patients undergoing gastric bypass, 420 had obstructive sleep apnea and 159 were dependent on CPAP. There were 15 major anastomotic leaks, two of which occurred in CPAP-treated patients. Contingency table analysis demonstrated that there was no correlation between CPAP utilization and the incidence of major anastomotic leakage (P = 0.6). Notably, no episodes of pneumonia were diagnosed in either group. Despite the theoretical risk of anastomotic injury from pressurized air delivered by CPAP, no anastomotic leaks occurred that were attributable to CPAP. There were no pulmonary complications in a patient population that is at risk for developing them postoperatively. CPAP is a useful modality for treating hypoventilation after RYGB without increasing the risk of developing postoperative anastomotic leaks.

Adult↗