Postprandial acylated ghrelin status following fat and protein manipulation of meals in healthy young women

The aim of the present study was to investigate the postprandial effect of diet composition on circulating acylated ghrelin levels in healthy women. A randomized cross-over study of three experimental treatments was performed. A total of 11 healthy young women of normal body weight completed the study. All 11 subjects consumed three iso-energetic meals of different macronutrient composition, a balanced meal (50% carbohydrates, 30% fat and 20% protein), a high-fat meal (45% carbohydrates, 45% fat and 10% protein) and a high-protein meal (45% carbohydrates, 20% fat and 35% protein), for breakfast on separate days. The test meals were administered 1 month apart. Blood samples were withdrawn immediately before and at 15, 30, 60, 120 and 180 min after the test meal for measurement of plasma acylated ghrelin, as well as serum glucose, insulin and triacylglycerol (triglyceride) levels. Acylated ghrelin fell significantly after ingestion of both the balanced and high-protein meals. Ghrelin persisted at significantly lower levels than baseline for a longer duration following the high-protein meal (P<0.05 at 15, 30, 60 and 120 min) compared with the balanced meal (P<0.05 at 30 and 60 min). Moreover, acylated ghrelin levels correlated negatively with the postprandial insulin levels. In conclusion, postprandial changes in acylated plasma ghrelin depend on the macronutrient composition of the meal and are possibly influenced by insulin.     

PET imaging of brain with the β-amyloid probe, [11C]6-OH-BTA-1, in a transgenic mouse model of Alzheimer’s disease

Purpose The purpose of this study was to evaluate the capacity of [¹¹C]6-OH-BTA-1 and positron emission tomography (PET) to quantify -amyloid (A) plaques in the Tg2576 mouse model of Alzheimers disease (AD).Methods PET imaging was performed with the NIH ATLAS small animal scanner in six elderly transgenic mice (Tg2576; age 22.0±1.8 months; 23.6±2.6 g) overexpressing a mutated form of human -amyloid precursor protein (APP) known to result in the production of A plaques, and in six elderly wild-type litter mates (age 21.8±1.6 months; 29.5±4.7 g). Dynamic PET scans were performed for 30 min in each mouse under 1% isoflurane inhalation anesthesia after a bolus injection of 13–46 MBq of [¹¹C]6-OH-BTA-1. PET data were reconstructed with 3D OSEM. On the coronal PET image, irregular regions of interest (ROIs) were placed on frontal cortex (FR), parietal cortex (PA), striatum (ST), thalamus (TH), pons (PO), and cerebellum (CE), guided by a mouse stereotaxic atlas. Time–activity curves (TACs) (expressed as percent injected dose per gram normalized to body weight: % ID-kg/g) were obtained for FR, PA, ST, TH, PO, and CE. ROI-to-CE radioactivity ratios were also calculated. Following PET scans, sections of mouse brain prepared from anesthetized and fixative-perfused mice were stained with thioflavin-S.Results TACs for [¹¹C]6-OH-BTA-1 in all ROIs peaked early (at 30–55 s), with radioactivity washing out quickly thereafter in both transgenic and wild-type mice. Peak uptake in all regions was significantly lower in transgenic mice than in wild-type mice. During the later part of the washout phase (12–30 min), the mean FR/CE and PA/CE ratios were higher in transgenic than in wild-type mice (1.06±0.04 vs 0.98±0.07, p=0.04; 1.06±0.09 vs 0.93±0.08 p=0.02) while ST/CE, TH/CE, and PO/CE ratios were not. Ex vivo staining revealed widespread A plaques in cortex, but not in cerebellum of transgenic mice or in any brain regions of wild-type mice.Conclusion Marked reductions in brain uptake of this radioligand in transgenic mice may be due to reduced cerebral blood flow relative to that in wild-type mice. Specific [¹¹C]6-OH-BTA-1 binding to A plaques, if any, is probably very low, as reflected in the small FR/CE and PA/CE ratio differences. FR/CE and PA/CE ratios are considerably higher in AD patients while A plaque densities in 22-month-old transgenic mice may be expected to show essentially the same density as is observed in the AD brain. This implies that the absence of tracer retention in 22-month-old transgenic mice may be due to the smaller number of A plaque binding sites and/or to lower affinity of the binding sites for [¹¹C]6-OH-BTA-1 as compared with AD patients. [¹¹C]6-OH-BTA-1 shows excellent brain uptake in mice.This work was presented at the 51st Annual Meeting of the Society of Nuclear Medicine in Philadelphia, PA, June 19–23, 2004.     

Quantification of cellular proliferation in tumor and normal tissues of patients with breast cancer by [18F]fluorothymidine-positron emission tomography imaging: evaluation of analytical methods

There is an unmet need to develop imaging methods for the early and objective assessment of breast tumors to therapy. 3'-Deoxy-3'-[18F]fluorothymidine ([18F]FLT)-positron emission tomography represents a new approach to imaging thymidine kinase activity, and hence, cellular proliferation. We compared graphical, spectral, and semiquantitative analytic methodologies for quantifying [18F]FLT kinetics in tumor and normal tissue of patients with locally advanced and metastatic breast cancer. The resultant kinetic parameters were correlated with the Ki-67 labeling index from tumor biopsies. [18F]FLT accumulation was detected in primary tumor, nodal disease, and lung metastasis. In large tumors, there was substantial heterogeneity in regional radiotracer uptake, reflecting heterogeneity in cellular proliferation; radiotracer uptake in primary tumors also differed from that of metastases. [18F]FLT was metabolized in patients to a single metabolite [18F]FLT-glucuronide. Unmetabolized [18F]FLT accounted for 71.54 +/- 1.50% of plasma radioactivity by 90 minutes. The rate constant for the metabolite-corrected net irreversible uptake of [18F]FLT (Ki) ranged from 0.6 to 10.4 x 10(-4) and from 0 to 0.6 x 10(-4) mL plasma cleared/s/mL tissue in tumor (29 regions, 15 patients) and normal tissues, respectively. Tumor Ki and fractional retention of radiotracer determined by spectral analysis correlated with Ki-67 labeling index (r = 0.92, P < 0.0001 and r = 0.92, P < 0.0001, respectively). These correlations were superior to those determined by semiquantitative methods. We conclude that [18F]FLT-positron emission tomography is a promising clinical tool for imaging cellular proliferation in breast cancer, and is most predictive when analyzed by graphical and spectral methods.     

Pulmonary hypertension in sickle cell anemia. A case report

We report the case of a 33-years-girl with SCA and severe PH. She developed six month before admission, non productive cough and dyspnea. Physical examination at admission revealed shortness of breath and right heart ventricular failure. Electrocardiography showed sinus rhythm and an incomplete left bundle branch block. Chest roentgenography revealed cardiomegaly with cardiothoracic index at 0.66 and pulmonary infiltrates. Laboratory tests revealed an anemia with hemoglobin of 7.1 g/dl, white blood cell count of 12,500/mm, moderate renal failure (cretininemia = 178 mumol/l) and hypoxemia with oxygen pressure of 60 mmHg. Hemoglobin electrophoresis revealed on heterozygous SCA. Echocardiography revealed dilatation of right heart cavities and a systolic pulmonary artery pressure of 60 mmHg. A perfusion lung scintigraphy demonstrated multiple subsegmental perfusion defects. PH is a common complication of adult patients with SCA. Appropriate therapies and strategies for prevention of PH in SCA are unknown. Further research exploring therapies such as oxygen, nitric oxide, prostacyclin and hydroxyurea are indicated.     

Chest wall tumors presenting as breast lumps

Two recently seen patients presenting with large breast lumps that proved to be pure mesenchymal tumors arising from the underlying chest wall are presented. One tumor proved to be a giant cell tumor of soft tissue and the other an osteogenic sarcoma. It is suggested that these two cases may not be unique and that some mesenchymal breast tumors might have their origin in the chest wall. Breast computed tomography (CT) scans would help identify similar cases.     

Interaction between NOTCH4 and catechol-O-methyltransferase genotypes in schizophrenia patients with poor response to typical neuroleptics

OBJECTIVE: In this study we attempted to show that the interaction between NOTCH4 and catechol-O-methyltransferase (COMT) polymorphism predicts the response to typical neuroleptics in schizophrenia. Our sample consisted of 94 Finnish patients with DSM-IV schizophrenia and 98 controls. METHODS: Several studies have connected COMT and NOTCH4 genes to schizophrenia. We have previously shown that COMT polymorphism is significantly associated with treatment response in schizophrenia. NOTCH4 SNP2 polymorphism has been associated with age of onset in schizophrenia, but there is also a trend that this polymorphism may predict response to typical neuroleptics. In the present sample, there is a strong gene-gene interaction between these genes (P = 0.003) and they have additive effect in treatment response. RESULTS: Patients carrying both NOTCH4 C/C genotype and COMT low/low genotype, had more than ten times higher risk of being a non-responder than responder to treatment with typical neuroleptics [OR = 10.25 (95% CI 2.21-47.53), P < 0.001]. This combination of genotypes is also more common in patients considered non-responders than in controls [OR = 3.00 (95% CI 1.33-6.76), P = 0.007]. CONCLUSION: Our results suggest that an interaction between COMT and NOTCH4 genotypes may predict the treatment response to typical neuroleptics in patients with schizophrenia.     

Gastric cancer with lymphoid stroma: a rare form associated with Epstein-Barr virus. Five cases

We report the cases of 5 patients with gastric cancer with lymphoid stroma, aged from 40 to 66 years. The tumor was located in the upper and the middle third of stomach in four patients. Using in situ hybridization, the tumor was Epstein-Barr virus-positive in all patients whereas immunohistochemical analysis was negative. Four patients had total gastrectomy associated in two cases with splenectomy and caudal pancreatic resection. The last patient had subtotal gastrectomy. One patient was lost to follow-up. After a mean follow-up of 31 months, 4 patients are alive and free of local recurrence.     

Oral solution of levodopa ethylester for treatment of response fluctuations in patients with advanced Parkinson's disease.

Levodopa ethylester (LDEE), a highly soluble prodrug of levodopa, may overcome the impaired absorption of regular levodopa, due mainly to a combination of levodopa's poor solubility and delayed gastric emptying. We conducted a double-blind, levodopa-controlled, multicenter study of oral LDEE solution compared with standard levodopa-carbidopa (LD-CD) tablets. Sixty-two patients with Parkinson's disease who had "delayed on" and "no-on" subtypes of response fluctuations were randomly assigned for treatment with LDEE-CD or LD-CD 250/25 mg for 4 weeks (phase A). Only the first morning and first post-lunch dose of LD were replaced. This was followed by a 2-week extension with a supplementation of carbidopa (25 mg) to each replaced dose (phase B). Patients filled home diaries 2 weeks before and during the trial period in which times of turning on and off for the two doses were reported. In phase A, mean latency to turning on was reduced by 21% (morning dose) and 17% (post-lunch dose) in the LDEE-CD group. Percentage of no-on episodes after the post-lunch dose was decreased by 21% in the LDEE-CD group but increased by 36% in the LD-CD group (P < 0.01). In phase B, LDEE-CD decreased latencies to on after the morning and post-lunch doses and no-on episodes after the post-lunch dose. The beneficial effects of LDEE were supported by the pharmacokinetic data. Results indicate that LDEE solution is beneficial in ameliorating delayed on and no-on response fluctuations. This effect of LDEE is due to more rapid levodopa absorption.