Elevated Serum Ghrelin Exerts an Orexigenic Effect that May Maintain Body Mass Index in Patients with Metastatic Neuroendocrine Tumors

Ghrelin is a potent orexigenic peptide principally produced in the stomach by a distinct population of neuroendocrine cells in the oxyntic mucosa of the fundus. Exogenous ghrelin given as an intravenous infusion has been shown to increase caloric intake in patients with cancer cachexia. In this study, we hypothesized that elevated endogenous ghrelin, produced by increased neuroendocrine cell tumor burden, also exerts an orexigenic effect helping to maintain body mass index. To evaluate the effect of elevated endogenous ghrelin, 35 patients with neuroendocrine tumors were enrolled, assigning them to one of two groups depending on the presence of hepatic metastases. Following an overnight fast, serum was collected and sent for ghrelin measurement by an outside laboratory. The two groups were well matched for all other relevant clinical variables including subtype of tumor, primary location of tumor and tumor treatment history. Nearly all patients with hepatic metastases had elevated levels of ghrelin compared to the standard reference range given for matched controls. The presence of hepatic metastases was associated with significantly elevated ghrelin levels (p<0.05) and a greater mean body mass index. In addition, we report a positive correlation between serum ghrelin and total tumor surface area and between serum ghrelin and body mass index, suggesting that elevated endogenous ghrelin may be sufficient to overcome any partial ghrelin resistance typically seen in cancer cachexia. These results support the possibility that ghrelin is co-released from neuroendocrine tumors and exerts an orexigenic effect in these patients, helping to maintain their body mass index despite widely disseminated disease. Presented at the Joint Meeting Summer Neuropeptide Conference July 1st, 2006 in Miami Beach, FL.     

铀矿接尘人员矽肺发生的特点

目的 了解铀矿接尘人员矽肺发生的规律与特点。方法 利用单因素分析法对核工业矿山与地质系统间、纯铀矿与混铀矿接尘人员间,矽肺患者的发病工龄、发病年龄、病程及死亡年龄进行分析。结果 随着时间的推移,铀矿接尘人员的发病工龄、发病年龄、病程及死亡年龄均延长。地质系统的矽肺Ⅰ期患者的发病工龄、发病年龄分别为(10.15±5.95)年、(40.60±9.86)岁,短于矿山系统的患者[(14.23±8.12)年、(41.38±10.98)岁];地质系统的矽肺Ⅰ期患者的病程(P50)及死亡年龄分别为14.29年及(53.69±10.04)岁,长于矿山系统的患者[12.52年及(51.45±10.85)岁]。纯铀矿的矽肺Ⅰ期患者的发病工龄为(11.78±8.06)年,发病年龄为(38.04±9.89)岁,短于混铀矿的患者[(12.74±6.29)年、(41.40±10.67)岁];纯铀矿的矽肺Ⅰ期患者的病程(P50)为14.59年,死亡年龄为(53.93±10.60)岁,均长于混铀矿的患者[13.20年、(51.82±10.20)岁]。结论地质系统与矿山系统、纯铀矿及混铀矿接尘者矽肺发生情况的差别可能与所接触粉尘的理化性质及各自的工作环境有关。     

Rabeprazole produces rapid, potent, and long-acting inhibition of gastric acid secretion in subjects with Helicobacter pylori infection

AIM: To compare acid inhibiting activity and duration of action of different doses of rabeprazole, a substituted benzimidazole characterized as a highly potent and irreversible H+, K+-ATPase inhibitor, administered for 7 days to subjects infected with Helicobacter pylori. METHODS: A total of 38 subjects (mean age 39.3 years) were enrolled in a single-centre, double-blind, randomized, crossover study. All subjects were confirmed positive for H. pylori by 14C urea breath test and ELISA serologies. Subjects were divided into two groups of 19 to receive two doses of rabeprazole, either 5 and 20 mg or 10 and 40 mg, and placebo, given in random order daily in the morning for 7 days. Peptone-stimulated acid, pH, and gastrin measurements were made for 24 h after the 1st dose and for 48 h after the 7th dose. RESULTS: Peptone-stimulated acid secretion rates were decreased from 12.5 to 6.7, 4.0, 1.5, and 0.26 h after initial 5, 10, 20, and 40 mg doses, respectively; to 7.3, 4.3, 2.1, and 1.2 mmol/h 23 h after the initial dose; and to 2.4, 2.6, 0.6, and 0.8 mmol/h 23 h after the 7th dose. After 48 h, stimulated acid secretion had recovered less than 40% for all treatment groups compared to placebo. Median intragastric pH also increased from 2.0 with placebo to 4.9, 6.2, 6.6 and 6.9 during the 24-h period after the 7th dose of 5, 10, 20, and 40 mg. The 20 mg dose of rabeprazole produced equivalent acid inhibition to the 40 mg dose with less increase in plasma gastrin. CONCLUSION: Rabeprazole in doses from 5 to 40 mg was a highly effective inhibitor of gastric acid secretion in subjects infected with H. pylori. The inhibition was rapid, dose-related, and long-acting, with less than 50% recovery of acid by 48 h after the 7th dose. The optimal acid inhibitory dose in these subjects appeared to be 20 mg daily, however 5 mg and 10 mg doses produced potent inhibition of gastric acid secretion.     

DIURNAL EFFECTS OF FLUOXETINE AND NALOXONE ON THE HUMAN HYPOTHALAMIC-PITUITARY-ADRENAL AXIS

1. Central serotonergic pathways are hypothesized to be involved in the stimulation of hypothalamic adrenocorticotropic hormone (ACTH) secretagogue release by both circadian- and stress-induced mechanisms. We aimed to investigate this hypothesis by measuring the effect of the highly specific serotonin re-uptake inhibitor fluoxetine (FX) on ACTH and Cortisol release in the morning and in the afternoon in humans, both by itself and in combination with the opioid antagonist naloxone (Nal). Naloxone causes ACTH release in humans by removing an endogenous inhibitory opioid tone on central noradrenergic pathways stimulatory to hypothalamic corticotropin-releasing hormone (CRH) secretion. Serotonergic agents may act directly or indirectly through these central noradrenergic pathways and, if so, would be expected to be additive to or synergistic with Nal in causing ACTH and Cortisol release. 2. Oral FX (40 mg) was given at approximately 07.00 or 11.00 h, either alone or with intravenous Nal 3 h later, to normal human volunteers. Plasma ACTH and Cortisol levels were measured for 5 h after FX dosing. 3. Fluoxetine produced a small but non-significant increase in Nal-stiimilated ACTH and Cortisol release in both morning and afternoon studies. Naloxone alone did not cause different ACTH and Cortisol responses in the morning and afternoon. 4. These results suggest that serotonergic pathways are not major regulators of the hypothalamic-pituitary-adrenal axis in humans or that FX has counteracting acute inhibitory effects on the axis, such as inhibition of hypothalamic arginine vasopressin secretion, which has been demonstrated in chronic animal studies.     

The novel use of an intravenous proton pump inhibitor in a patient with short bowel syndrome.

Recent evidence suggests that parenteral proton pump inhibitors (PPIs) can effectively control gastric acid hypersecretion. Intravenous PPI (omeprazole) can substantially reduce the risk of recurrent bleeding in patients with peptic ulcer disease. We describe a patient with short bowel syndrome who had recurrent life-threatening upper gastrointestinal bleeding from severe gastric and esophageal ulcerations. The patient had failed long-term, maximal-dose intravenous ranitidine therapy but was successfully treated and maintained on long-term therapy with an intravenous PPI (pantoprazole). To our knowledge, this is the first case report in the literature describing the use of an intravenous PPI to treat upper gastrointestinal bleeding in a patient with complete intestinal resection. Intravenous PPIs should be considered as the first line of treatment of erosive esophagitis and peptic ulcer disease in patients with short bowel syndrome and in patients who are nil per os and who fail intravenous H 2 -receptor antagonist treatment. Parenteral PPI may also be the drug of choice in intensive care patients who have erosive esophagitis. Furthermore, this is the first case report describing the novel use of intravenous pantoprazole to treat erosive esophagitis in a patient with short bowel syndrome, suggesting that intravenous PPI may also be useful for the treatment of ulcer prophylaxis in patients undergoing intestinal transplantation.     

Body mass index development during the first 6 months of life in infants born to human immunodeficiency virus-seropositive mothers

The development of body mass index (BMI) was measured during the first 6 months of life in three groups of infants [human immunodeficiency virus (HIV) -uninfected, n = 92; later symptomatic HIV-infected, n = 18; early symptomatic HIV-infected, n = 9] born to HIV-positive mothers and compared with a reference group (n = 65) born to healthy mothers. A trend towards lower values in the two groups of HIV-infected infants was already evident at birth. Among the four groups, HIV-uninfected infants showed the highest BMI values while the early-infected infants showed the lowest BMI values at all measurements. The later-infected group had a value close to the reference at 1 month, and then increased at slower rates than the uninfected and the reference groups. Infants born to HIV-positive mothers may have higher energy and nutrient requirements after birth, either to sustain an increased BMI development (when uninfected) or to meet catabolic mechanisms (when infected).     

Gingival granulomatosis with polyangiitis (Wegener's granulomatosis) as a primary manifestation of the disease

Granulomatosis with polyangiitis (GPA) is a potentially lethal disease characterized by systemic necrotizing vasculitis, which affects small‐ and medium‐sized blood vessels and is often associated with serum cytoplasmic antineutrophil cytoplasmic antibody. The upper and lower respiratory tract and kidney are the most involved sites, but oral lesions can be identified in 6–13% of the cases, whereas in only 2% of the cases, oral manifestations represent the first signal of the disease usually as gingival swellings or unspecific ulcerations. Without treatment, the mainstay of which is the combination of immunosuppressants and systemic corticosteroids, GPA may run a fatal course. In this report we describe an original case of GPA affecting a 75‐year‐old female patient referred to our service due to a gingival swelling with 3‐month duration. Although the patient was correctly diagnosed and promptly treated, she died 3 months after the initial diagnosis.