1H MRS studies in the Finnish boron neutron capture therapy project: detection of 10B-carrier, L-p-boronophenylalanine-fructose

This article summarizes the current status of 1H MRS in detecting and quantifying a boron neutron capture therapy (BNCT) boron carrier, L-p-boronophenylalanine-fructose (BPA-F) in vivo in the Finnish BNCT project. The applicability of 1H MRS to detect BPA-F is evaluated and discussed in a typical situation with a blood containing resection cavity within the gross tumour volume (GTV). 1H MRS is not an ideal method to study BPA concentration in GTV with blood in recent resection cavity. For an optimal identification of BPA signals in the in vivo 1H MR spectrum, both pre- and post-infusion 1H MRS should be performed. The post-infusion spectroscopy studies should be scheduled either prior to or, less optimally, immediately after the BNCT. The pre-BNCT MRS is necessary in order to utilise the MRS results in the actual dose planning.     

Caveolins as tumour markers in lung cancer detected by combined use of cDNA and tissue microarrays

To identify new potential diagnostic markers for lung cancer, the expression profiles of 37 lung tumours were analysed using cDNA arrays. Seven samples were from small-cell lung cancer (SCLC), two from large-cell neuroendocrine tumours (LCNEC), and 28 from other non-small-cell lung cancers (mainly squamous cell cancer and adenocarcinoma). Principal component analysis and the permutation test were used to detect differences in the gene expression profiles and a set of genes was found that distinguished high-grade neuroendocrine carcinomas (SCLC and LCNEC) from other lung cancers. In addition, several genes, such as caveolin-1 (CAV1) and caveolin-2 (CAV2), were constantly deregulated in all types of tumour sample, compared with normal tissue. The expression of these two genes was investigated further at the protein level on a tissue microarray containing tumours from 161 patients and normal tissues. Immunostaining for CAV1 was negative in 48% of tumours, whereas 28% of the tumours did not express CAV2. Lack of CAV1 protein expression was not caused by methylation or mutation. In stage I adenocarcinomas, CAV2 protein expression correlated with shorter survival. In conclusion, the present study was able to identify genes that have not previously been implicated in lung cancer by the combined use of two different array techniques. Some of these genes may provide novel diagnostic markers for lung cancer.     

Growth hormone selectively improves intestinal cholesterol absorption after jejunoileal autotransplantation in pigs

Background/Purpose

Small bowel transplantation impairs enteric function and causes malabsorption of cholesterol and bile acids. Growth hormone stimulates intestinal absorptive function. The authors hypothesized that long-term growth hormone therapy could improve absorption of bile acids and cholesterol after autotransplantation of the jejunoileum.

Methods

Sixteen pigs with similar food, cholesterol, and fat intake underwent either sham laparotomy or a model of jejunoileal autotransplantation, including extrinsic autonomic denervation, lymphatic interruption, and in situ cold ischemia. Five randomly chosen autotransplanted animals received daily growth hormone treatment for 8 weeks. Serum lipids, absorption, and excretion of cholesterol, bile acids, and fat were determined after 8 weeks. Mucosal morphometrics, proliferation, and enzyme activities were determined. Plasma cholesterol precursors and plant sterols, respective markers of cholesterol synthesis and absorption, were measured after 2 and 8 weeks.

Results

After jejunoileal autotransplantation, growth hormone treatment significantly increased body weight gain, cholesterol absorption efficiency from 45.1% to 62.1%, plasma campesterol to cholesterol proportions, and biliary secretion of cholesterol. With or without growth hormone treatment, autotransplantation significantly increased fecal bile acid excretion, plasma cholesterol precursors, fecal bacterially modified neutral sterols, mucosal thickness of the ileum (but not jejunum), and intestinal transit time when compared with sham-operated animals. Crypt cell proliferation, mucosal enzyme activities, and microvilli showed no differences between the groups.

Conclusions

These findings suggest that growth hormone treatment selectively improves cholesterol, but not bile acid absorption, after autotransplantation of the jejunoileum.     

Diabetes as an independent risk factor for early postoperative complications in critical limb ischemia

OBJECTIVE: The purpose of this study was to evaluate the significance of diabetes mellitus as a risk factor for postoperative major morbidity and mortality after surgery for critical lower limb ischemia (CLI). SUBJECTS: A national vascular registry (Finnvasc)-based survey included 5709 operations for CLI from 1991 through 1999. Of these operations, 2508 (44%) were performed on diabetics. Tissue loss was the indication for surgery in 77% of diabetics and in 52% of nondiabetics. The proportion of femorodistal bypasses was 43% in diabetics and 24% in nondiabetics, whereas the proportion of reconstructions for aortofemoral arterial occlusive disease was 16% in diabetics and 34% in nondiabetics. RESULTS: Thirty-day mortality was 4.5% in diabetics and 3.4% in nondiabetics ( P = .05). The rate for early below-knee amputation was 6.5% in diabetics and 3.3% in nondiabetics ( P < .001). Independent factors for postoperative death were aortofemoral reconstruction (odds ratio [OR], 4.0), preoperative cardiac risk factor (OR, 3.1), primary surgery (OR, 2.0), renal insufficiency (OR, 1.9), urgent surgery (OR, 1.7), and age (OR, 1.3). Diabetes was an independent risk factor for postoperative below-knee amputation (OR, 1.7), cardiac complications (OR, 1.5), and superficial wound infection (OR, 1.3). There was an inverse association between diabetes and acute graft occlusion (OR, 0.8). Independent risk factors for early postoperative mortality in diabetes were aortofemoral reconstruction (OR, 2.5), urgent surgery (OR, 2.0), male gender (OR, 2.0), renal insufficiency (OR, 1.9), cardiac risk factor (OR, 1.7), and age (OR, 1.4). In nondiabetics independent risk factors for early postoperative mortality were aortofemoral reconstruction (OR, 4.5), cardiac risk factor (OR, 3.6), primary surgery (OR, 2.6), and extra-anatomic bypass (OR, 2.3). CONCLUSIONS: Diabetes was not an independent risk factor for early postoperative mortality in CLI as there was an increased morbidity in diabetics associated with old age, male gender, known coronary artery disease, and renal insufficiency, as well as urgent surgery. As diabetics have increased proclivity for these factors, special attention needs to be paid to their preoperative assessments.     

Maternal smoking in pregnancy, fetal development, and childhood asthma

OBJECTIVES: We examined the relationships among maternal smoking in pregnancy, fetal development, and the risk of asthma in childhood. METHODS: We conducted a population-based cohort study, where all 58 841 singleton births were followed for 7 years using nationwide registries. RESULTS: Maternal smoking increased the risk of asthma (adjusted odds ratio = 1.35; 95% confidence interval = 1.13, 1.62 for high exposure). Low birthweight and preterm delivery increased the risk of asthma at the age of 7, whereas being small for gestational age did not. CONCLUSIONS: Maternal smoking in pregnancy increases the risk of asthma during the first 7 years of life, and only a small fraction of the effect seems to be mediated through fetal growth.     

A method for assessing occupational dermal exposure to permanent hair dyes

Hairdressers have an increased risk of developing occupational skin diseases due to exposure to skin irritants and sensitizers. In the present work a method of assessing dermal exposure to permanent hair dyes was developed. The sampling performance characteristics of hand wash sampling with bag rinsing were studied for five hair dye compounds. The effect of residence time, sample load and different matrices were studied. Thirty volunteers were exposed to a reference solution of these compounds and to commercial hair dye products. The sampling efficiency after 5 min residence time was between 70 and 90% for the dye components in the hair dye products. Sampling efficiency decreases with increasing residence time, making the time of sampling an important factor. Hand wash sampling should be performed as soon as possible after the work task of interest. We conclude that the sampling efficiency is adequate for measurements of dermal exposure to permanent hair dyes. Hand wash sampling with bag rinsing is a useful tool for field studies of dermal exposure assessment in hairdressers.     

Postnatal development of resistance to short-term high-dose toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in TCDD-resistant and -semiresistant rats

Despite great interspecies differences in adult 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) sensitivity, the toxic potency of TCDD is similar across species in fetal mortality. Han/Wistar (Kuopio; H/W) rats are exceptionally resistant to acute toxicity of TCDD, but show sensitivity to embryotoxicity and teratogenicity. The resistance of adult H/W rats to acute TCDD toxicity is based on a point mutation in the transactivation domain of the aryl hydrocarbon receptor (AHR) and to an unknown gene “B”. This study investigated the time course of postnatal development of resistance to TCDD and the significance of genotypic variation in resistance development. H/W, line A (a new line with the H/W-type mutated AHR), and line B rats (a line with normal AHR but moderately resistant because of gene “B”) were exposed to a single dose of TCDD 2-56 days after birth. H/W and line A rats received 1000 μg/kg; male and female B rats received 200 and 100 μg/kg, respectively. Survival was monitored for 42 days. Interestingly, although TCDD ceased growth and weight gain in all TCDD groups, the younger dosed animals did not seem to reach the body weight of the older dosed animals even in 100 days. The survival results after 42 days showed that line A rats are fairly resistant to TCDD immediately after birth, and their full TCDD resistance develops during the first week of life. The moderate resistance of line B rats develops approximately at the time of weaning. This difference in the time course of resistance development suggests that there are basic differences in pathways mediating resistance in lines A and B rats.     

Life events, social support, and onset of major depressive episode in Finnish patients

We investigated differences in life events and social support between subgroups of depressed patients and the distribution of life events in phases preceding or during depression. In the Vantaa Depression Study, 269 psychiatric patients with DSM-IV major depressive disorder were diagnosed with Schedule for Clinical Assessment in Neuropsychiatry, Version 2.0, and Structured Clinical Interview for DSM-III-R personality disorders (SCID-II). Life events during the 12 months preceding the interview were investigated with the Interview for Recent Life Events, and social support with the Interview Measure of Social Relationships and the Perceived Social Support Scale-Revised. Nearly all patients (91%) reported life events, on average 4.1 per preceding year. No major differences between sociodemographic or clinical subgroups were found; the frequency of events was somewhat greater among the younger subjects, whereas those with comorbid alcoholism or personality disorders perceived less social support. Although events were distributed evenly between the time preceding depression, the prodromal phase, and the index major depressive episode, two thirds of the patients attributed their depression to some event. Despite clinical and sociodemographic heterogeneity, patients with major depressive disorder are fairly homogeneous in terms of life events during the preceding year. Events do not cluster in any particular phase of the progression to an episode.     

Nasal swab versus nasopharyngeal aspirate for isolation of respiratory viruses

To determine the usefulness of nasal swabs as a simple method for detection of respiratory viruses, we compared nasal swabs and nasopharyngeal aspirates obtained at the same time from the opposite nostrils of 230 children with upper respiratory infection. The sensitivity of nasal swabs was comparable to that of nasopharyngeal aspirates for the detection of all major respiratory viruses except respiratory syncytial virus.     

Alpha-adrenoceptor-mediated modulation of 5-HT2 receptor agonist induced impulsive responding in a 5-choice serial reaction time task

The activation of 5-HT2A receptors has been shown to enhance the probability of premature responding, regarded as a form of motor impulsive behaviour. At the behavioural level, the interaction of alpha-adrenoceptors and 5-HT2 receptors has been linked to head twitch behaviour, regarded as an experimental model of compulsive behaviour. The aim was to determine whether the probability of premature responding induced by an excess activation of 5-HT2A receptors can be modulated by the blockade of alpha1- or alpha2- adrenoceptors. In the experiments, the 5-choice serial reaction time task was used to measure attention and response control of the rats. The experiments assessed the effects of (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) 0.1-0.2 mg/kg subcutaneously, a 5-HT2A/2C agonist, and prazosin, an alpha1-adrenoceptor antagonist, alone or in combination, on the performance of rats. In an additional experiment to examine the possible role of the alpha2-adrenoceptors, a potent, selective and specific alpha2-adrenoceptor antagonist, atipamezole, was given alone or in combination with DOI. Results showed that DOI increased the probability of premature responses, but it did not affect the choice accuracy. Prazosin (0.1 or 0.3 mg/kg, subcutaneously), given on its own had no effects on probability of responding prematurely, but prazosin (0.3 mg/kg.) was able to attenuate the DOI-induced responding. Atipamezole (0.1 mg/kg, s.c.) did not attenuate the effect of DOI on probability of premature responding. When given at lower doses, DOI (0.03 mg/kg) and atipamezole (0.03 mg/kg) synergistically increased the probability of premature responding, whereas a higher dose of atipamezole (0.3 mg/kg) on its own increased the probability of responding prematurely, but this effect was not additive to that of 0.1 mg/kg DOI. These data indicate that 5-HT2 receptor activation enhances impulsive responding and this effect can be diminished by the blockade of alpha1-adrenoceptors. Atipamezole, an alpha2-antagonist, enhances the probability of premature responding and shares the mechanism of action with the 5-HT2 agonist in this respect. These results provide evidence for an interaction between the serotonergic 5-HT2 receptors and alpha-adrenoceptors in the modulation of response control to the motor impulsivity type of behaviour (premature responding) in addition to that of compulsory behaviour (head shakes) found previously.