Weight loss after bariatric surgery normalizes brain opioid receptors in morbid obesity.

Positron emission tomography (PET) studies suggest opioidergic system dysfunction in morbid obesity, while evidence for the role of the dopaminergic system is less consistent. Whether opioid dysfunction represents a state or trait in obesity remains unresolved, but could be assessed in obese subjects undergoing weight loss. Here we measured brain µ-opioid receptor (MOR) and dopamine D2 receptor (D2R) availability in 16 morbidly obese women twice-before and 6 months after bariatric surgery-using PET with [(11)C]carfentanil and [(11)C]raclopride. Data were compared with those from 14 lean control subjects. Receptor-binding potentials (BPND) were compared between the groups and between the pre- and postoperative scans among the obese subjects. Brain MOR availability was initially lower among obese subjects, but weight loss (mean=26.1 kg, s.d.=7.6 kg) reversed this and resulted in ~23% higher MOR availability in the postoperative versus preoperative scan. Changes were observed in areas implicated in reward processing, including ventral striatum, insula, amygdala and thalamus (P's<0.005). Weight loss did not influence D2R availability in any brain region. Taken together, the endogenous opioid system plays an important role in the pathophysiology of human obesity. Because bariatric surgery and concomitant weight loss recover downregulated MOR availability, lowered MOR availability is associated with an obese phenotype and may mediate excessive energy uptake. Our results highlight that understanding the opioidergic contribution to overeating is critical for developing new treatments for obesity.

Temperament, character and serotonin activity in the human brain: a positron emission tomography study based on a general population cohort.

BACKGROUND: The psychobiological model of personality by Cloninger and colleagues originally hypothesized that interindividual variability in the temperament dimension 'harm avoidance' (HA) is explained by differences in the activity of the brain serotonin system. We assessed brain serotonin transporter (5-HTT) density in vivo with positron emission tomography (PET) in healthy individuals with high or low HA scores using an 'oversampling' study design. Method Subjects consistently in either upper or lower quartiles for the HA trait were selected from a population-based cohort in Finland (n = 2075) with pre-existing Temperament and Character Inventory (TCI) scores. A total of 22 subjects free of psychiatric and somatic disorders were included in the matched high- and low-HA groups. The main outcome measure was regional 5-HTT binding potential (BPND) in high- and low-HA groups estimated with PET and [11C]N,N-dimethyl-2-(2-amino-4-methylphenylthio)benzylamine ([11C]MADAM). In secondary analyses, 5-HTT BPND was correlated with other TCI dimensions. RESULTS: 5-HTT BPND did not differ between high- and low-HA groups in the midbrain or any other brain region. This result remained the same even after adjusting for other relevant TCI dimensions. Higher 5-HTT BPND in the raphe nucleus predicted higher scores in 'self-directedness'. CONCLUSIONS: This study does not support an association between the temperament dimension HA and serotonin transporter density in healthy subjects. However, we found a link between high serotonin transporter density and high 'self-directedness' (ability to adapt and control one's behaviour to fit situations in accord with chosen goals and values). We suggest that biological factors are more important in explaining variability in character than previously thought.

Eutrophication and self-purification: counteractions forced by large-scale cycles and hydrodynamic processes.

During the 1990s nitrogen reserves have shown rising trends in the northern Baltic Sea. Changes in denitrification explain some of the fluctuations observed in nitrogen reserves. Although denitrification is an anaerobic process, the most efficient removal of nitrogen by denitrification occurs where the sediment is moderately well oxidized. A dramatic decrease in the ratio of SiO4 to DIN (DIN = NO3 + NH4) in the northern Baltic proper during the period 1973-1999 was recorded. If dissolved silica limits phytoplankton spring bloom, diatom blooms fade and become replaced by flagellates leading to changes in summer phosphate reserves and sedimentation. Seven years have elapsed from the previous strong saltwater inflow and anoxia has spread over large areas. Deep bottom phosphorus levels have started to increase and denitrification capacity is weakening. Thus, all efforts to minimize N- and P-loading will, in the long run, help the Baltic Sea to recover from the unacceptable status of eutrophication.

The role of bacteria in the nutrient exchange between sediment and water in a flow-through system.

The contribution of bacteria to phosphorus (P) and nitrogen (N ) release from, or retention in, sediment was studied in a flow-through system. "Live" and formaldehyde-"killed" sediment communities were incubated in 25-liter bottles with a continuous flow of P- or P + N-enriched water. Sediment bacteria in the killed communities were inhibited by adding formaldehyde (final concentration 0.04% v/v) to the sediment before the start of the experiment. Bacterial activity in the live sediments measured with [(3)H]thymidine and [(14)C]leucine incorporation techniques did not change essentially during the experiment period (7-8 days). Chemical mechanisms were found to be of principal importance in PO4-P retention in the sediment. In the live samples, the net retention of PO4-P was lower than in the killed samples, which was likely due to the reduced O2 conditions in the sediment as a consequence of bacterial mineralization. In total P exchange, however, bacteria increased the retention rate by recycling dissolved organic P in the sediment. In the live communities the retention of N was very efficient, and all the introduced NH4 -N and NO3-N was immobilized by sediment bacteria. Nitrogen enrichment, however, did not alter the P exchange rates. The gradual emergence of bacterial activity (and grazing) in the killed communities, subsequent to the dilution of formaldehyde concentration, enhanced the release of PO4-P and NH4-N from sediment.

Comparison of methods for inhibiting bacterial activity in sediment.

Dilute formaldehyde was the most suitable treatment to inhibit sediment bacteria, since bacterial activity remained low during long-term incubations and the chemical changes in the sediment were minimal. The inhibiting effects of HgCl(2), autoclaving, and gamma radiation were diminished during longer incubations; these treatments also caused increases in dissolved nutrients.

Clinical, histological and quantitative prognostic factors in cutaneous malignant melanoma.

A retrospective study including 55 cutaneous melanoma patients with 9.5 years follow-up was carried out to assess the significance of various prognostic factors. The histological samples were evaluated according to Clark's and Breslow's classifications and six nuclear features were measured by interactive morphometry. Mitotic activity was assessed by two different methods: mitotic activity index (MAI) and volume corrected mitotic index (M/V index). The overall disease-related five-year survival of patients was 76.4%. TNM stage (p = 0.0001), sex (p = 0.0024), M/V index (p = 0.003), standard deviation of nuclear form factor (p = 0.023), MAI (p = 0.02), shortest nuclear axis (p = 0.023) and Breslow's classification (p = 0.044) predicted survival in univariate analysis. A multivariate analysis including clinical, histological and morphometric features pointed the Clark's classification as the most important predictor of survival (p = 0.002), while the other variables included had no independent prognostic value. The prognostic importance of mitotic indices and morphometric features is clearly a subject for further studies in superficial melanomas.

Melanoma of palms, soles, and nail-beds.

The clinical and histological characteristics of palmar, plantar, and subungual melanomas treated in the division of plastic surgery of Helsinki University Hospital between 1970 and 1984 were analysed. The peak incidence was during the seventh decade of life, and the mean delay between the onset of symptoms and the diagnosis was one year. The delay was as much the fault of the physician as of the patient. The observed and relative five-year-survival rates for all 31 patients were 60% and 67%, and the 10-year-survival rates 39% and 49%, respectively. There were 15 cases of the acral lentiginous subtype, and the observed and relative five-year-survival rates were 65% and 71%, and the 10-year-survival rates 48% and 64%, respectively. For the nodular melanomas (n = 11) the survival rates were 53% and 60%, and 39% and 53%, respectively. For the three superficial spreading melanomas they were 50% and 52%, and 25% and 28%, respectively. Microstaging criteria (Breslow and Clark) were both good prognostic indicators. The series was too small for multivariate analysis.

Simultaneous hepatoblastoma in identical male twins.

Identical male twin infants who in 1987 presented with hepatoblastoma at the age of 7 months are reported. Twin B was admitted for investigation due to enlarged liver and spleen. He was found to have an inoperable hepatoblastoma of fetal type and was treated with chemotherapy and local irradiation. However, 7 months after the chemotherapy the tumor recurred. The asymptomatic twin A was examined because of the known familial cases, and he proved to have an identical tumor. He was successfully radically operated on and 2 years after the chemotherapy is still doing well with no evidence of tumor. As the mother and the maternal grandmother had polyps in the colon, quite probably the hepatoblastomas of the twins were associated with familial adenomatous polyposis.

Carcinoma of the breast in children.

Carcinoma of the breast in children is an extremely rare disease, only 44 patients have been reported in the world literature. We report on a case of breast cancer in a 9-year-old girl, who was admitted to the hospital because of a four-month history of a painless mass in the right breast. Clinical examination and mammography resulted in a strong suspicion of malignancy. The histology corresponded to juvenile secretory carcinoma, the histological type without the characteristics of prepubertal cancer cases. Electron microscopy demonstrated intracellular large vacuoles and acini filled with secretory material. The mitotic index was low, the highest measured value was 4 mitotic figures per 10 high power fields corresponding to 2.78 mitotic figures per mm2 of epithelium in the microscope field. Flow cytometry showed that the neoplastic cells were diploid and had a low S-phase fraction. A simple mastectomy including axillary evacuation was performed. No lymph node or distant metastases were found. Postoperative radiation treatment or chemotherapy were not administered. Our patient has been in follow-up for six years without recurrence. In this case simple mastectomy with axillary evacuation seems to have given a cancer-free development into adulthood. Earlier reports have also shown a favourable outcome in these tumours.

A suggested follow-up time for breast cancer patients.

The data for this study, consisting of 300 females treated for breast cancer in 1951-1961, were evaluated in order to ascertain when excess mortality from breast cancer disappears and what would be an appropriate follow-up period for investigational purposes. The clinical stages of the patients were classified as follows: 23.3%, stage I; 49%, stage II; 20.3%, stage III and 7.3%, stage IV. Halsted's radical mastectomy was performed in 79.7% of the cases. Every patient was given radiotherapy. Two hundred and ninety-eight patients could be followed until death or up to the present. Forty-five patients (16%) were still alive. The survival rate over a 20-year period for the various stages was as follows: stage I, 46.1%; stage II, 22.7% and stage III, 10.9%. Only 26% of the patients with stage I died of breast cancer, while the respective figures for stage II were 57% and stage III, 70%. The death rate from the cancer diminished with time in every stage especially 10 years after primary treatment. After this the observed survival rate curves were almost parallel with the expected curves. Our data show that for follow-up studies a 5-year follow-up is good and a 10-year follow-up is very good to show the trend in the treatment of breast cancer.