Cytomorphologic features of metastatic urothelial carcinoma in serous effusions.

Metastatic urothelial carcinoma (UC) to serous effusion (SE) is extremely rare and its cytomorphological features have only been described in case reports. In this study, we searched the pathology database at University of Michigan for SEs due to metastatic UC in the last 20 years. A total of 25 cases from 20 patients with clinically and pathologically confirmed metastatic UC in SEs were retrieved. The specimens consisted of 15 pleural, 8 peritoneal, and 2 pericardial effusions. Smears were reviewed and evaluated for the following features: cellularity, single cells, cell clusters or short cords, cell wrapping, "windows" between the cells, two-tone cytoplasm, cytoplasmic vacuoles, signet ring cells, nuclear to cytoplasmic (N/C) ratio, nuclear hyperchromasia, irregular nuclear membrane, nuclear centricity, double or multiple nuclei, nucleoli, anaplastic cells and mitosis. Our results showed that UC manifested in SEs predominantly as a single cell population with or without clusters or short cords, and frequently exhibited the "cell wrapping" of two or more cells. Individual UC cell in SEs exhibited nuclear enlargement with increased N/C ratio, irregular nuclear membranes, hyperchromatic coarse chromatin and frequently prominent nucleoli. Double or multinucleated cells, cells with vacuolated cytoplasm or signet ring appearance were also frequently present. Our results demonstrated that while certain features could suggest the diagnosis of UC, the cytomorphological features are not specific and often overlap with those of reactive mesothelium, mesothelioma, metastatic adenocarcinoma, or squamous cell carcinoma in SEs. Accurate diagnosis of UC rests on the combination of clinical history, cytomorphologic features and appropriate immunohistochemical panel.

Methylnaltrexone reduced body weight gain in ob/ob mice.

OBJECTIVE: Opioids may function to regulate food intake and body weight, an activity that could be predominantly centrally mediated. In this study, the authors evaluated the effects of a peripherally acting opioid receptor antagonist, methylnaltrexone, on weight changes in adult obese ob/ob mice. RESULTS: After a 12-day treatment with naloxone 0.3 mg/kg, weight was reduced from 63.7 +/- 1.1 g in the control group to 59.2 +/- 0.9 g in the naloxone group (p < 0.05). After a 12-day treatment with methylnaltrexone 3.0 mg/kg, weight increase completely ceased. The body weight was 63.9 +/- 1.0 g in the control group when compared with 55.9 +/- 1.2 g in the drug group (p < 0.01). The effect of methylnaltrexone (1.0 mg to 3.0 mg/kg) on weight changes was dose-dependent (p < 0.01). Methylnaltrexone significantly reduced daily food intake (p < 0.05), but did not affect body temperature and energy expenditure. Using HPLC analysis, no detectable naltrexone levels were found in association with methylnaltrexone administration. Whether the observed methylnaltrexone effects are primarily related to the antagonism of endorphinergic system remains to be investigated. CONCLUSIONS: Our results suggest that the peripheral opioid mechanism contributes to modulating food ingestion and methylnaltrexone may have clinical importance in obesity management.

Methylnaltrexone potentiates body weight and fat reduction with leptin.

OBJECTIVE: Leptin increases energy expenditure by enhancing systemic and brown adipose metabolism. In a neonatal rat model, retroperitoneal fat pad weight decreased significantly in leptin-treated animals, which reduced body weight. As opioids increase feeding, opioid antagonists may decrease food intake and body weight. However, interactions between leptin and the activity of peripheral opioids on body weight and fat accumulation have not been investigated. In this study, the authors evaluated the effects of naloxone (a nonselective opioid antagonist) and methylnaltrexone (a peripherally acting opioid antagonist) on the action of leptin in neonatal rats. RESULTS: Compared with control, the weight gain of pups given a single daily intraperitoneal injection of leptin 0.5 mg/kg, leptin 0.5 mg/kg plus naloxone 0.3 mg/kg, or leptin 0.5 mg/kg plus methylnaltrexone 3.0 mg/kg for 8 consecutive days was significantly reduced (all p < 0.01). Naloxone or methylnaltrexone significantly potentiated leptin's effect on body weight (p < 0.05 or p < 0.01, respectively). After coadministration of leptin plus naloxone or leptin plus methylnaltrexone, weight reduction in the right retroperitoneal fat pads was also significant compared with the reduction after leptin alone (p < 0.05 or p < 0.01, respectively). CONCLUSIONS: The data suggest the existence of a peripheral opioid-related mechanism in leptin-active modulation of body weight.

Extranodal natural killer/t-cell lymphoma, nasal type, in a patient with a constitutional 11q terminal deletion disorder.

BACKGROUND: Most cases of constitutional 11q terminal deletion disorder are children. Malignancy is a potential concern, as these children reach adulthood. However, since the majority of patients are young, their risk of developing malignancy in adulthood is essentially unknown. AIM: To report the first hematologic malignancy [extranodal natural killer (NK)/T-cell lymphoma, nasal type] arising in the trachea of a patient with constitutional 11q terminal deletion disorder. Our patient is the oldest patient reported in the literature. It is of note that this cytogenetic abnormality has not been described as a recurring abnormality in extranodal NK/T-cell lymphoma. CASE REPORT: A 36-year-old male with congenital psychomotor retardation was transferred to our hospital. Pathologic evaluation was diagnostic of extranodal NK/T-cell lymphoma, nasal type. Staging marrow was negative for lymphoma, but cytogenetic analysis revealed a constitutional deletion of chromosome 11 at band q23 [46,XY,del(11)(q23)(c)]. This abnormality was present in a subsequent bone marrow specimen, along with an acquired abnormality, namely an extra copy of part of the long arm of chromosome 1 translocated to the short arm of chromosome 14. CONCLUSION: Patients with 11q terminal deletion disorder who reach adulthood may be predisposed to develop neoplasias by virtue of the constitutional deletion.

Analgesic effects of different acupoint stimulation frequencies in humans.

Transcutaneous electrical acupoint stimulation (TEAS) provides a convenient and standardized technique for pain treatment. The cold-pressor test is a simple and reliable model in humans for the induction of tonic pain. In this controlled study, the effects of TEAS on cold pressor-induced pain were evaluated in 22 healthy human subjects. Electrical stimulation at 4 Hz and 32 Hz was applied to He-Gu (LI 4) and Nui-Guan (P 6) acupoints for 15 minutes. Pain score ratings were evaluated at four time points from 30-170 seconds during the cold-pressor test. We observed an analgesic effect at both 4 Hz and 32 Hz of stimulation, and pain score rating reductions were statistically significant compared to control (p < 0.01). Our data support the efficacy of TEAS analgesia. However, there was no significant difference between pain scores at 4 Hz and 32 Hz stimulation.

Transcutaneous electrical acupoint stimulation potentiates analgesic effect of morphine.

Pain is the major complaint of patients who choose acupuncture treatment. Transcutaneous electrical acupoint stimulation (TEAS) provides a safe, standardized technique without needle insertion. TEAS can be tested with the cold-pressor test, a simple, reliable, and widely used model in humansfor the induction of tonic pain. In this controlled study, the effects of TEAS on cold-pressor-induced pain were evaluated in 20 healthy human subjects. Electrical stimulation electrodes were applied to He-Gu (LI 4) and Nui-Guan (P 6) acupoints. The effects of saline plus no TEAS, 15-minute TEAS alone, 0.05 mg/kg morphine alone, and 15-minute TEAS plus morphine were assessed. Pain score ratings were evaluated at four time points from 30 to 170 seconds during the cold-pressor test. The authors observed analgesic effects in both TEAS-alone and morphine-alone sessions, and pain score rating reductions were statistically significant compared to unstimulated control (both p < 0.01). The degree of TEAS analgesia combined with 0.05 mg/kg morphine was significantly higher than TEAS alone (p < 0.01). The results support the efficacy of TEAS analgesia and suggest that combination of TEAS with low-dose morphine can achieve better pain control in a variety of clinical settings.

Antidiabetic effects of Panax ginseng berry extract and the identification of an effective component.

We evaluated antihyperglycemic and anti-obese effects of Panax ginseng berry extract and its major constituent, ginsenoside Re, in obese diabetic C57BL/6J ob/ ob mice and their lean littermates. Animals received daily intraperitoneal injections of Panax ginseng berry extract for 12 days. On day 12, 150 mg/kg extract-treated ob/ob mice became normoglycemic (137 +/- 6.7 mg/dl) and had significantly improved glucose tolerance. The overall glucose excursion during the 2-h intraperitoneal glucose tolerance test decreased by 46% (P < 0.01) compared with vehicle-treated ob/ob mice. The improvement in blood glucose levels in the extract-treated ob/ ob mice was associated with a significant reduction in serum insulin levels in fed and fasting mice. A hyperinsulinemic-euglycemic clamp study revealed a more than twofold increase in the rate of insulin-stimulated glucose disposal in treated ob/ ob mice (112 +/- 19.1 vs. 52 +/- 11.8 micromol x kg(-1) x min(-1) for the vehicle group, P < 0.01). In addition, the extract-treated ob/ob mice lost a significant amount of weight (from 51.7 +/- 1.9 g on day 0 to 45.7 +/- 1.2 on day 12, P < 0.01 vs. vehicle-treated ob/ob mice), associated with a significant reduction in food intake (P < 0.05) and a very significant increase in energy expenditure (P < 0.01) and body temperature (P < 0.01). Treatment with the extract also significantly reduced plasma cholesterol levels in ob/ob mice. Additional studies demonstrated that ginsenoside Re plays a significant role in antihyperglycemic action. This antidiabetic effect of ginsenoside Re was not associated with body weight changes, suggesting that other constituents in the extract have distinct pharmacological mechanisms on energy metabolism.

Leptin, gut, and food intake.

Hyperphagia (overeating) is often associated with energy over-storage and obesity, which may lead to a myriad of serious health problems, including heart disease, hypertension, and type 2 diabetes. Thus, understanding the complex pathological mechanisms underlying hyperphagia and obesity has an important clinical significance. Leptin, or ob protein, is a key element in the long-term regulation of food intake and body weight homeostasis. It circulates in the blood at levels correlated with body fat mass. Leptin binds to specific receptors in the hypothalamus to mediate events that regulate feeding behavior. In light of new evidence, the initial view that leptin is an adipocyte-derived signal, which acts centrally to decrease body weight, has been modified. It has been shown that leptin may also have specific functions in the gastrointestinal tract, suggesting that feeding and energy homeostasis is regulated by both central and peripheral signals. Evidence supports the view that leptin integrates short-term, meal-related signals from the gut into long-term regulation of energy balance. In addition, the gastric leptin level is altered by the nutritional state and the administration of cholecystokinin. This commentary aims to review the evidence of the role of leptin as a peripherally acting signal in the gut in the regulation of nutrient intake, adiposity, and body weight. Based on currently available data, some potential future studies are suggested.

Alternative therapies for type 2 diabetes.

Type 2 diabetes is a chronic metabolic disease that has a significant impact on the health, quality of life, and life expectancy of patients, as well as on the health care system. Exercise, diet, and weight control continue to be essential and effective means of improving glucose homeostasis. However, lifestyle management measures may be insufficient or patient compliance difficult, rendering conventional drug therapies (i.e., oral glucose-lowering agents and insulin injection) necessary in many patients. In addition to adverse effects, drug treatments are not always satisfactory in maintaining euglycemia and avoiding late stage diabetic complications. As an alternative approach, medicinal herbs with antihyperglycemic activities are increasingly sought by diabetic patients and health care professionals. Commonly used herbs and other alternative therapies, less likely to have the side effects of conventional approaches for type 2 diabetes, are reviewed.