Fructose:Glucose Ratios—A Study of Sugar Self-Administration and Associated Neural and Physiological Responses in the Rat

This study explored whether different ratios of fructose (F) and glucose (G) in sugar can engender significant differences in self-administration and associated neurobiological and physiological responses in male Sprague-Dawley rats. In Experiment 1, animals self-administered pellets containing 55% F + 45% G or 30% F + 70% G, and Fos immunoreactivity was assessed in hypothalamic regions regulating food intake and reward. In Experiment 2, rats self-administered solutions of 55% F + 42% G (high fructose corn syrup (HFCS)), 50% F + 50% G (sucrose) or saccharin, and mRNA of the dopamine 2 (D2R) and mu-opioid (MOR) receptor genes were assessed in striatal regions involved in addictive behaviors. Finally, in Experiment 3, rats self-administered HFCS and sucrose in their home cages, and hepatic fatty acids were quantified. It was found that higher fructose ratios engendered lower self-administration, lower Fos expression in the lateral hypothalamus/arcuate nucleus, reduced D2R and increased MOR mRNA in the dorsal striatum and nucleus accumbens core, respectively, as well as elevated omega-6 polyunsaturated fatty acids in the liver. These data indicate that a higher ratio of fructose may enhance the reinforcing effects of sugar and possibly lead to neurobiological and physiological alterations associated with addictive and metabolic disorders.     

Goal-directed fluid therapy for microvascular free flap reconstruction following mastectomy: A pilot study

BACKGROUND:

Fluid management of the surgical patient has undergone a paradigm shift over the past decade. A change from ‘wet’ to ‘dry’ to a ‘goal-directed’ approach has been witnessed. The fluid management of patients undergoing free flap reconstruction is particularly challenging. This is typically a long operation with minimal surgical stimulation, and hypotension often ensues. The use of vasopressors in these cases is contraindicated to maintain adequate flow to the flap. Hypotension is often treated with intravenous fluid boluses. However, aggressive fluid administration to maintain adequate blood pressure can result in flap edema, venous engorgement and, ultimately, flap loss.

OBJECTIVE:

The primary objective of the present study was to determine whether goal-directed fluid therapy, titrated to maintain stroke volume variation ≤13%, with the use of an arterial pulse contour device results in improved postoperative cardiac index (CI) and stroke volume index (SVI) with reduced amounts of intravenous fluid. The primary end points studied were CI, SVI and cumulative crystalloid/colloid administration.

METHODS:

Twenty female patients undergoing simultaneous microvascular free flap reconstruction immediately following mastectomy were studied. Preoperative and intraoperative care were standardized. Each patient received intra-arterial blood pressure monitoring. In all patients, cardiac output measurement occurred throughout the intraoperative period using the arterial pulse contour device. Control patients had their fluid administered at the discretion of the anesthesiologist (blinded to results from the cardiac output device). Patients in the intervention group had a baseline crystalloid infusion of 5 mL/kg/h, with intravenous colloid boluses to maintain a stroke volume variation ≤13%.

RESULTS:

There was no difference in heart rate or mean arterial pressure between groups at the end of the operation. However, at the end of the operation, the intervention group had significantly higher mean (± SD) CI (3.8±0.8 L/min/m² versus 3.0±0.5 L/min/m²; P=0.02) and SVI (51.4±2.4 mL/m² versus 43.3±2.3 mL/m²; P=0.03). This improved CI and SVI was achieved with similar amounts of administered intraoperative fluid (5.8±0.5 mL/kg/h versus 5.0±0.7 mL/kg/h, control versus intervention). The intervention group required less postoperative fluid resuscitation during the early postoperative period (total fluid administered from end of operation to midnight of the operative day, 6.4±1.9 mL/kg/h versus 10.2±3.3 mL/kg/h, intervention versus control, respectively, P<0.01).

DISCUSSION:

Goal-directed fluid therapy using minimally invasive cardiac output monitoring resulted in improved end-operative hemodynamics, with less ‘rescue’ fluid administration during the perioperative period.     

Neoadjuvant Therapy for Rectal Cancer: Histologic Response of the Primary Tumor Predicts Nodal Status

PURPOSE: This study was designed to compare histologic T and N stages in patients with rectal adenocarcinoma undergoing various neoadjuvant radiotherapy regimens and proctectomy, in an attempt to determine if final histologic stage of the mural tumor predicts nodal status.METHODS: Data were collected from computerized databases at two institutions on 649 consecutive patients who underwent neoadjuvant radiotherapy or chemoradiotherapy and proctectomy for primary adenocarcinoma of the rectum from 1990 to 2002.RESULTS: Five patients were excluded because of incomplete pathology data sets, leaving a study population of 644. Patients underwent neoadjuvant radiotherapy alone (2,000 cGy in 5 fractions, n = 191; or 4,500 cGy in 25 fractions, n = 259) or chemoradiation (4,500 cGy in 25 fractions with concurrent 5-fluorouracil, n = 194). Histologic stage of the remaining mural tumor (ypT) correlated with nodal status (ypN). Lymph nodes harboring metastatic tumor were found in 1 of 42 (2 percent) ypT0 patients, 2 of 45 (4 percent) ypT1 patients, 43 of 186 (23 percent) ypT2 patients, 158 of 338 (47 percent) ypT3 patients, and 16 of 33 (48 percent) ypT4 patients (P < 0.001, chi-squared test). The probability of finding ypN+ disease was 3 of 87 (3 percent) in patients with ypT0-1 residual primary tumors vs. 220 of 557 (39 percent) in patients with ypT2-4 residual primary tumors (P < 0.0001; Fishers exact test).CONCLUSIONS: Nodal metastases are rare in patients whose mural tumor burden shrinks to ypT0-1 after neoadjuvant radiotherapy. If transanal excision is offered to select patients with distal rectal cancer, it is reasonable to select those who have an excellent clinical response to neoadjuvant therapy for transanal excision, and then reserve proctectomy for patients proven to have residual ypT2-4 disease.Read at the meeting of The American Society of Colon and Rectal Surgeons, New Orleans, Louisiana, June 21 to 26, 2003.     

Cathepsin S genotypes are associated with Apo-A1 and HDL-cholesterol in lean and obese French populations

Cathepsin S (CTSS) is a cysteine protease that has a central role in remodeling the extracellular matrix and, as such, has been implicated in the etiology of cardiovascular disease. This study used five tag single nucleotide polymorphisms (tSNPs) to screen the CTSS gene in healthy lean ( n  = 1891) and obese French populations ( n  = 477) for their association with various phenotypes: body mass index, waist-to-hip ratio, glycemia, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (Apo-A1) and apolipoprotein B. Significant associations were identified between rs11576175 tSNP (A/G) and Apo-A1 and HDL-C plasma levels in a sex-specific manner. Lean female subjects homozygous for the minor A-allele had higher levels of circulating Apo-A1 (p = 0.0003), while lean male A/A carriers had higher levels of HDL-C (p = 0.007) compared with the other genotypes. In the obese cohort, associations were found between three tSNPs and Apo-A1 levels in adult female subjects: rs10888390 (G/A), p = 0.01; rs10888394 (T/C), p = 0.03; and rs1136774 (C/T), p = 0.02; however, only rs10888390 remained significant in a combined model (p = 0.03). These results provide the first evidence that CTSS sequence variations are associated with two human metabolic risk factors for cardiovascular diseases: plasma Apo-A1 and HDL-C concentrations.     

Ovarian cancer patient surveillance after curative-intent initial treatment

Objective

Patient surveillance after potentially curative treatment of ovarian carcinoma has important clinical and financial implications for patients and society. The optimal intensity of surveillance for these patients is unknown. We aimed to document the current follow-up practice patterns of gynecologic oncologists.

Methods

We created four idealized vignettes describing patients with stages I-III ovarian cancer. We mailed a custom-designed survey instrument based on the vignettes to the members of the Society of Gynecologic Oncologists (SGO). SGO members were asked, via this instrument, how often they requested 11 discrete follow-up evaluations for their patients for the first 10 postoperative years after treatment with curative intent.

Results

We received 283 evaluable responses (30%) from the 943 SGO members and candidate members. The most frequently performed items for each year were office visit, pelvic examination, and serum CA-125 level. Imaging studies such as chest X-ray, abdominal-pelvic CT, chest CT, abdominal-pelvic MRI, and transvaginal ultrasound were rarely recommended. There was marked variation in the frequency of use of most tests. There was a decrease in the frequency of testing over time for all modalities.

Conclusion

This dataset provides detailed documentation of the self-reported surveillance practices of highly credentialed experts who manage patients with ovarian cancer in the 21st century. The optimal follow-up strategy remains unknown and controversial. Our survey showed marked variation in surveillance intensity. Identifying the sources of this variation warrants further research.