Carbon-11-methionine and PET is an effective method to image head and neck cancer.

Methionine metabolism is altered in cancer, and methionine labeled with 11C has been successfully used for imaging of brain, lung, and breast cancer and lymphoma. Uptake of L-[methyl-11C]methionine (11C-methionine) in head and neck cancer of 23 patients was studied with PET. Accumulation of 11C-methionine in the tumors was assessed by two different methods: the influx constant, Ki, and the standardized uptake value (SUV). All 23 cancers accumulated 11C-methionine. The mean Ki was 0.147 +/- 0.070 min-1 and the mean SUV 8.5 +/- 3.5. There was a strong correlation between the two measures of tumor uptake (r = 0.92, p less than 0.0001). There was no correlation between the uptake of 11C-methionine and the histological grade of cancer. Head and neck cancer can thus be effectively imaged with 11C-methionine. Carbon-11-methionine PET imaging may be useful in delineating tumors for therapy planning.     

Three cases of severe verapamil poisoning

Three cases of verapamil intoxication are described. The first two patients took 6.4 g verapamil each and the third one took 0.8 g of verapamil and alcohol. All three developed a third-degree atrioventricular dissociation, the first patient developed a slow idioventricular rhythm without atrial activity, the second a temporary asystole. All were hypotensive, had anuria and shock, the first two were unconscious for several hours. The first one was treated with artificial cardiac pacing, orciprenaline and calcium gluconate, the second with cardiac pacing and orciprenaline. The third patient received fluids and a dopamine infusion. In the first case sinus rhythm returned 31 h after the swallowing of tablets, in the second after 32 h and in the third after 10 h. Pacing with intensive monitoring and care seemed to be the most beneficial treatments in these cases.     

Polymorphisms in Inflammation-related Genes and Risk of Gastric Cancer (Finland)

Helicobacter pylori infection is an important risk factor for gastric cancer, but <3% of carriers of this organism will ever develop gastric cancer. Since inflammation plays a significant role in gastric carcinogenesis, it has been suggested that polymorphisms in genes involved in inflammatory response may partly explain why only a subgroup of patients infected with H. pylori develop gastric cancer. We compared relative frequencies of 17 single nucleotide polymorphisms (SNPs) in eight inflammation-related genes between 112 gastric cancer patients and 208 controls. Cases and controls were selected from a large cohort of Finnish male smokers who were recruited into the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. The studied SNPs were IL-1A (−889 C/T), IL-1B (−511 C/T and −31 T/C), IL-6 (−174 G/C and −597 G/A), IL-8 (−251 T/A, +396 T/G and +781 C/T), IL-8RA (Ex2 +860 G/C), IL-8RB (Exon 3 +1235 T/C, Exon 3 +811 C/T, and Exon 3 +1010 G/A), IL-10 (−819 C/T, −592 C/A, −1082 A/G), and TNF A (−308 G/A, −238 G/A). We found no statistically significant association between any of these SNPs, or the number of pro-inflammatory polymorphisms, with risk of gastric cancer. Our results do not support the hypothesis that polymorphisms in genes involved in the inflammatory response confer differences in gastric cancer risk among different individuals.     

Thymosin beta4 is a determinant of the transformed phenotype and invasiveness of S-adenosylmethionine decarboxylase-transfected fibroblasts

S-adenosylmethionine decarboxylase (AdoMetDC) is a key enzyme in the synthesis of polyamines essential for cell growth and proliferation. Its overexpression induces the transformation of murine fibroblasts in both sense and antisense orientations, yielding highly invasive tumors in nude mice. These cell lines hence provide a good model to study cell invasion. Here, the gene expression profiles of these cells were compared with their normal counterpart by microarray analyses (Incyte Genomics, Palo Alto, CA, and Affymetrix, Santa Clara, CA). Up-regulation of the actin sequestering molecule thymosin beta4 was the most prominent change in both cell lines. Tetracycline-inducible expression of thymosin beta4 antisense RNA caused a partial reversal of the transformed phenotype. Further, reversal of transformation by dominant-negative mutant of c-Jun (TAM67) caused reduction in thymosin beta4 mRNA. Interestingly, a sponge toxin, latrunculin A, which inhibits the binding of thymosin beta4 to actin, was found to profoundly affect the morphology and proliferation of the AdoMetDC transformants and to block their invasion in three-dimensional Matrigel. Thus, thymosin beta4 is a determinant of AdoMetDC-induced transformed phenotype and invasiveness. Up-regulation of thymosin beta4 was also found in ras-transformed fibroblasts and metastatic human melanoma cells. These data encourage testing latrunculin A-like and other agents interfering with thymosin beta4 for treatment of thymosin beta4-overexpressing tumors with high invasive and metastatic potential.     

A prospective study of anthropometric and clinical measurements associated with insulin resistance syndrome and colorectal cancer in male smokers

Type 2 diabetes mellitus shares risk factors for and has shown a positive association with colorectal cancer. Anthropometric measures (height, weight, and body mass index (weight (kg)/height (m)(2)) and metabolic abnormalities associated with insulin resistance syndrome (IRS) (abnormalities in measured blood pressure, high density lipoprotein (HDL) cholesterol, and total cholesterol) were prospectively evaluated for associations with incident colon (n = 227), rectal (n = 183), and colorectal (n = 410) cancers diagnosed between 1985 and 2002 in 28,983 Finnish male smokers from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals. In comparison with the lowest quintile, the highest quintile of body mass index was significantly associated with colorectal cancer (hazard ratio (HR) = 1.70, 95% confidence interval (CI): 1.01, 2.85; p-trend = 0.01), particularly colon cancer. Subjects with a cluster of three IRS-related conditions (hypertension, body mass index >/=25 kg/m(2), and HDL cholesterol level <40 mg/dl (<1.55 mmol/liter)), compared with those with fewer conditions, had a significantly increased risk of colorectal cancer (HR = 1.40, 95% CI: 1.12, 1.74), particularly colon cancer (HR = 1.58, 95% CI: 1.18, 2.10), but not rectal cancer. These results support the hypothesis that the significant association observed between IRS-defining metabolic abnormalities and colorectal cancer is determined primarily by adiposity.     

Low metacarpal index predicts hip fracture: a prospective population study of 3,561 subjects with 15 years of follow-up

Background Metacarpal index (MCI), measured from hand radiographs as the ratio between combined cortical thickness and bone diameter, has been suggested for assessment of bone mass and risk of osteoporotic fracture. We studied MCI for its ability to predict hip fractures.

Methods Hand radiographs were taken and MCI determined in 3,561 subjects from a representative population sample of 8,000 Finns who were 30 years of age or over in 1978-80. Record linkage to the National Hospital Discharge Register identified 117 subjects who had been hospitalized for primary treatment of hip fracture by the end of 1994.

Results High age, low body mass index, tall stature and smoking at baseline showed, independently of each other, significant associations with low MCI. Low MCI was a strong predictor of hip fracture. When adjusted for all potential confounding factors, the relative risk of hip fracture per decrement of MCI by one standard deviation (0.1) was 1.5 (95% CI 1.2-1.8).

Interpretation Low MCI is associated with known risk factors of osteoporosis and predicts hip fracture. Since hand radiographs are easily available at low cost, measurements of MCI can be used as an alternative approach to find osteoporotic individuals with a high risk of hip fracture. ▪     

A short questionnaire method for evaluation of diets

The objective of this study was to develop a short questionnaire for the evaluation of diets in practical public health settings. One hundred and fifty-four men and women kept food consumption records for 4 days and filled in a questionnaire concerning the types and frequencies of use of 24 food items. Food items best predicting the intakes of total fat, milk fat, sugar, alcohol, and their total intake were identified by stepwise regression analysis. The best predictors were the weekly frequencies of the following food items: total fat—slices of bread, glasses of milk, pork, pastry; milk fat—slices of bread with butter, glasses of milk, cups of coffee with milk or cream; sugar—lumps of sugar, pastry, juice, ice cream; alcohol—bottles of beer, liquor. The total intake of fat, sugar, and alcohol was best explained by the weekly frequencies of six of the above food items. The combined sum frequencies of the best predictors were negatively correlated with the intakes of vitamins and minerals per 1000 kcal. The present approach appears to be promising for classification of individuals on the basis of the quality of their diets. Further studies are needed to test the value of the questionnaire in other population groups.     

Searching for an assessment instrument to determine temporomandibular disorder pain profiles for the purposes of primary health care

The objective was to study the utility of the graded chronic pain (GCP) scale of the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) for the purpose of recognizing TMD pain profiles in primary health care. The GCP scale was used to gather data from 93 consecutive TMD patients seeking treatment in a primary health care setting. The GCP data were compared with pain profiles assessed by scales similar to the more complicated multidimensional pain inventory (MPI). The scales used were able to produce the similar 'dysfunctional profiles' in the TMD patients as the original MPI scale in the sample of chronic pain patients. Also, the original MPI profiles of 'adaptive copers' and 'interpersonally distressed' were produced with distinctive features. The GCP grades distributed almost identically among the subgroups produced by the pain profiles. Most grade I patients were classified as adaptive copers (82--86%), most grade II patients were interpersonally distressed (59%) and all except one of the grade III patients were classified as dysfunctional (83%). The results seem to support the main assumption of our study that the GCP scale is a simple screening tool suitable for identifying primary care TMD patients with various types of pain profiles.     

Liver echogenicity: relation to systemic blood pressure and other components of the metabolic syndrome

We studied the impact of liver echogenicity among other potential predictors of systemic blood pressure (BP) and the metabolic syndrome. 38 persons (32 males, six females, aged 29 to 66) had their liver echogenicities scored, BPs measured and standard serum laboratory tests studied. There was a significant correlation between both systolic (r=0.438, p=0.006) and diastolic (r=0.498, p=0.001) BP and liver echogenicity. Liver echogenicity was the strongest predictor for systolic BP and the second strongest (after body mass index, BMI) for diastolic BP. Body height may modify the relation between liver echogenicity and systolic BP. Liver echogenicity also correlated significantly with BMI (r=0.527, p=0.001), serum triglycerides (r=0.472, p=0.003) and, to a lesser degree, with serum total cholesterol (r=0.305, p=0.066). Incidentally found increased liver echogenicity should alert the US performer and the clinician reading the report on the possibility of elevated BP or other features of the metabolic syndrome.     

Increase in Ara-C cytotoxicity in the presence of valproate, a histone deacetylase inhibitor, is associated with the concurrent expression of cyclin D1 and p27(Kip 1) in acute myeloblastic leukemia cells

The effects of valproate and butyrate were investigated in an acute myeloblastic cell line (OCI/AML-2) on cytotoxicity, cell cycle profile and expression of cell cycle regulating proteins in the presence of cytarabine (Ara-C) and etoposide. As a single agent valproate and butyrate inhibited AML cell growth but did not significantly induce cell death. A dramatic increase in cytotoxicity was observed when combining valproate or butyrate with Ara-C, whereas, co-addition of them with etoposide had much smaller effect on cell death. Valproate induced a clear G1 phase arrest and up-regulated cyclin D1 expression in the presence of Ara-C and etoposide. In addition, valporate was able to block the Ara-C-induced down-regulation of p27(Kip1) expression but not that induced by etoposide.