The effect of unfiltered coffee on potential biomarkers for colonic cancer risk in healthy volunteers: a randomized trial

BACKGROUND: Epidemiologic studies suggest that coffee use might protect against colorectal cancer. Inconsistencies as to the effect of coffee use and colorectal cancer between epidemiologic studies might be related to the type of coffee brew. OBJECTIVE: We studied the effect of unfiltered coffee consumption on putative biomarkers for colonic cancer risk. DESIGN: A total of 64 healthy volunteers (31 men and 33 women), with a mean age of 43 +/- 11 years were randomly assigned to two groups in a crossover design, with two intervention periods of 2 weeks separated by a washout period of 8 weeks. Treatments were 1 L of cafetière (French press) coffee daily or no coffee. At the end of each intervention period, fasting blood samples, colorectal biopsies and 48 h faeces were collected. RESULTS: No effect of coffee on colorectal cell proliferation, assayed by estimating the Proliferating Cell Nuclear Antigen labelling index, was seen. Additionally, no effects were seen on the concentrations of faecal soluble bile acids and colorectal mucosal glutathione S-transferase activity. However, unfiltered coffee significantly increased the glutathione content in the colorectal mucosa by 8% and in plasma by 15%. Other aminothiols in plasma also increased on coffee. CONCLUSION: Unfiltered coffee does not influence the colorectal mucosal proliferation rate, but might increase the detoxification capacity and anti-mutagenic properties in the colorectal mucosa through an increase in glutathione concentration. Whether this effect indeed contributes to a lower colon cancer risk remains to be established.     

Distribution of components of the glutathione detoxification system across the human placenta after uncomplicated vaginal deliveries

The function of the glutathione-related detoxification system plays an important role to ensure an uncomplicated pregnancy outcome. This study was performed to investigate whether the components of the glutathione-related detoxification system are equally distributed among the different cotelydons in the human placenta. We measured glutathione, cysteine, glutathione S-transferase (GST) isoenzyme levels (GSTA1+A2, GSTP1, GSTM1 and GSTT1), enzyme activities of glutathione S-transferase and glutathione peroxidases, protein carbonyl levels, and antioxidant capacities at twelve different standardized positions in six placentae from healthy women after uncomplicated pregnancy and vaginal delivery. Data were statistically evaluated with a Friedman two-way ANOVA with Bonferroni correction. 'Foetal'-side values were not significantly different from those at the 'maternal'-side. Except for GSTA1+A2, no significant differences were found between different sampling sites indicating that the distribution of all parameters measured was homogenous throughout the placenta. Since levels of GSTA1+A2 were minor compared to those of GSTP1 and GSTT1, the clinical relevance of this heterogeneity may be limited. These results implicate that the location of sampling is not important as long as biopsies are taken from physiological cotelydons.     

Antireflux surgery normalizes cyclooxygenase-2 expression in squamous epithelium of the distal esophagus

BACKGROUND: In some patients GERD presents with heartburn and regurgitation symptoms but a relative paucity of endoscopic and clinical findings, while in others symptoms may be minor or absent yet there is significant mucosal damage on endoscopy including the presence of Barrett's esophagus. The initial injury of gastroesophageal reflux is to the squamous esophageal mucosa, but while substantial research has been devoted to determining which genes are involved in the progression of Barrett's to dysplasia and cancer, little is known about the gene expression alterations in the squamous mucosa of patients with reflux. We hypothesized that the expression of cyclooxygenase-2 (Cox-2) might be increased in the squamous esophageal mucosal of patients with reflux, and might be a molecular indicator of reflux injury. Further, we hypothesized that Cox-2 expression in the squamous mucosa would be reduced following the elimination of reflux with an antireflux operation. METHODS: Biopsies of the distal esophageal squamous mucosa were taken 3 cm above the squamocolumnar junction (SCJ) in 28 GERD patients before and after Nissen fundoplication. Following microdissection and RNA isolation, quantitative real-time PCR was used to measure Cox-2 gene expression in paraffin-embedded (N = 16) and fresh frozen (N = 12) tissue. Biopsies from patients (paraffin N = 15, frozen N = 14) with normal acid exposure and no evidence of mucosal injury were analyzed as controls. RESULTS: Median Cox-2 expression in the squamous epithelium from paraffin embedded biopsies in patients with reflux disease was significantly increased compared to controls (p = 0.04). The presence of esophagitis or Barrett's esophagus did not significantly alter the expression of Cox-2 compared to patients with nonerosive reflux disease (NERD). After antireflux surgery median Cox-2 expression values were significantly reduced (p = 0.0003) and were normalized to levels similar to controls without reflux (p = 0.74). Similar results were observed in the prospectively obtained fresh frozen tissue. CONCLUSIONS: Cox-2 gene expression is increased in the distal esophageal squamous mucosa of most patients with GERD, and the elevation was similar whether there was mucosal injury in the form of esophagitis or Barrett's or no visible mucosal injury. This suggests that increased Cox-2 expression may serve as a molecular marker of reflux disease. The increased Cox-2 expression in patients with reflux was usually normalized following antireflux surgery. These findings demonstrate for the first time that gene expression can be altered by surgical correction of reflux. Thus, in addition to symptom control and improvement in the quality of life, perhaps future studies assessing the efficacy of antireflux therapy should also focus on the impact of the therapy on gene expression in the esophageal squamous mucosa.     

Tuberculosis of the breast: rare but still extant. Review of the literature and report of an additional case

Tuberculosis of the breast is a rare malady that is usually manifested by a unilateral mass suggestive of carcinoma or sometimes of abscess. Mammography also suggests carcinoma in most instances. However, at operation, the discovery of necrotic tissue or abscess may lead to the suspicion of infectious or inflammatory disease rather than neoplasm. The diagnosis of tuberculosis may be established by the demonstration of acid-fast bacilli in excised tissue, by culture studies, or by guinea pig inoculation; however, the diagnosis is usually not suspected. In the past, mastectomy was the usual treatment. Today, successful treatment combines antituberculous drug therapy with the removal of infected breast tissue. The prognosis for complete cure is excellent. One case of secondary tuberculous mastitis has been reported herein. The patient, an Egyptian woman residing in the United States since 1973, was treated in Egypt for pulmonary tuberculosis at age 17. She presented in 1982 with a breast mass that mimicked carcinoma on physical examination and mammograms, but excisional biopsy and histologic examination revealed a breast abscess that contained caseous material and a solitary acid-fast bacillus. The patient was cured of her disease after appropriate operation and a course of antituberculous drugs. This has been the only documented case of mammary tuberculosis at our institution. Despite its rarity, tuberculosis of the breast should not be forgotten in this age of world travel.     

The normal mucosal surface pattern of the duodenal bulb: radiologic-histologic correlation

Similar to the stomach and colon, the duodenum also demonstrates a fine mucosal relief pattern on double-contrast radiographic examination. Two patterns may be identified--fine reticular and "small dot." In order to investigate the origin of these patterns, duodenal bulb specimens were obtained at autopsy, and macroscopic and microscopic features were correlated with radiographic patterns. Findings indicate that the surface patterns identified radiographically on cadaveric specimens and in live patient subjects are due to villi and the collections of barium within the intervening sulci. Knowledge of this normal pattern will prevent misdiagnoses, especially when inflammatory disease of the duodenum is being considered.     

Rectal acetaminophen does not reduce morphine consumption after major surgery in young infants

BACKGROUND: The safety and value of acetaminophen (paracetamol) in additionto continuous morphine infusion has never been studied in newbornsand young infants. We investigated the addition of acetaminophento evaluate whether it decreased morphine consumption in thisage group after major thoracic (non-cardiac) or abdominal surgery. METHODS: A randomized controlled trial was performed in 71 patients giveneither acetaminophen 90–100 mg kg^–1 day^–1orplacebo rectally, in addition to a morphine loading dose of100 µg kg^–1 and 5–10 µg kg^–1h^–1 continuous infusion. Analgesic efficacy was assessedusing Visual Analogue Scale (VAS) and COMFORT scores. Extramorphine was administered if VAS was 4. RESULTS: We analysed data of 54 patients, of whom 29 received acetaminophenand 25 received placebo. Median (25–75th percentile) agewas 0 (0–2) months. Additional morphine bolus requirementsand increases in continuous morphine infusion were similar inboth groups (P = 0.366 and P = 0.06, respectively). There wasno significant difference in total morphine consumption, respectively,7.91 (6.59–14.02) and 7.19 (5.45–12.06) µg kg^–1 h^–1for the acetaminophen and placebo group (P = 0.60). COMFORT[median (25–75th percentile) acetaminophen 10 (9–12)and placebo 11 (9–13)] and VAS [median (25–75thpercentile) acetaminophen 0.0 (0.0–0.2) and placebo 0.0(0.0–0.3)] scores did not differ between acetaminophenand placebo group (P = 0.06 and P = 0.73, respectively). CONCLUSIONS: Acetaminophen, as an adjuvant to continuous morphine infusion,does not have an additional analgesic effect and should notbe considered as standard of care in young infants, 0–2months of age, after major thoracic (non-cardiac) or abdominalsurgery.     

Muscle necrosis in the extremities: evaluation with Tc-99m pyrophosphate scanning--a retrospective review

A retrospective review was done of 34 extremities studied between 1981 and 1985 with technetium-99m pyrophosphate scanning; 22 were subsequently amputated. Results of detailed pathologic examination or immediate postoperative examination of the resected extremity were available in 16 cases. In these cases, scanning had allowed correct prediction of the level of amputation and of the specific areas of muscle infarction in 13 cases. In the one case in which amputation was performed for infection rather than muscle necrosis, the lack of necrosis was correctly predicted with the scan. The limited results of this study indicate that the Tc-99m pyrophosphate scan allows the location of necrotic muscle to be predicted accurately and may therefore be a useful adjunct in determining the best level for ultimate amputation. Special caution is required in those cases in which muscle necrosis is due to acute causes (e.g., traumatic thrombosis) rather than chronic vascular disease.     

Expression and immunogenicity of oncofetal antigen-immature laminin receptor in human renal cell carcinoma

PURPOSE: The 32 to 44 kDa. oncofetal antigen-immature laminin receptor (OFA-iLR) is a multifunctional protein expressed by various tumors, including breast, lung, ovary and prostate carcinoma as well as lymphoma. OFA-iLR has been implicated in tumor invasiveness, metastasis and growth. Interferon-gamma producing effector T cells and interleukin (IL)-10 producing suppressor T cells specific for OFA-iLR have been described. MATERIALS AND METHODS: The 43515 IgG2a anti-OFA-iLR monoclonal antibody was used to detect OFA-iLR expression in human renal cell carcinoma tissue by flow cytometry and immunoblotting. Spontaneous or therapy induced immune responses against OFA-iLR were determined in patients with metastatic renal cell carcinoma. Proliferative and cytokine (interferon-gamma and IL-10) responses of peripheral blood mononuclear cells from patients with renal cell carcinoma against recombinant OFA-iLR were assessed. RESULTS: Using flow cytometry OFA-iLR was detected in all 13 tumors tested. Immunoblotting revealed differences in OFA-iLR expression in renal cell carcinoma and normal kidney tissue. OFA-iLR specific proliferative and cytokine responses of mononuclear cells were detected in all 6 patients tested. Importantly evidence was also obtained that treating metastatic renal cell carcinoma with tumor lysate pulsed dendritic cells would enhance OFA-iLR specific immunity. CONCLUSIONS: This study demonstrates that OFA-iLR is an immunogenic tumor associated antigen in human renal cell carcinoma. OFA-iLR specific effector T cells producing interferon-gamma may have a role in the control of tumor growth, whereas suppressor T cells producing IL-10 may promote tumor tolerance and, thus, tumor progression.