Specificity of fungal associations of Pyroleae and Monotropa hypopitys during germination and seedling development.

Mycoheterotrophic plants obtain organic carbon from associated mycorrhizal fungi, fully or partially. Angiosperms with this form of nutrition possess exceptionally small 'dust seeds' which after germination develop 'seedlings' that remain subterranean for several years, fully dependent on fungi for supply of carbon. Mycoheterotrophs which as adults have photosynthesis thus develop from full to partial mycoheterotrophy, or autotrophy, during ontogeny. Mycoheterotrophic plants may represent a gradient of variation in a parasitism-mutualism continuum, both among and within species. Previous studies on plant-fungal associations in mycoheterotrophs have focused on either germination or the adult life stages of the plant. Much less is known about the fungal associations during development of the subterranean seedlings. We investigated germination and seedling development and the diversity of fungi associated with germinating seeds and subterranean seedlings (juveniles) in five Monotropoideae (Ericaceae) species, the full mycoheterotroph Monotropa hypopitys and the putatively partial mycoheterotrophs Pyrola chlorantha, P. rotundifolia, Moneses uniflora and Chimaphila umbellata. Seedlings retrieved from seed sowing experiments in the field were used to examine diversity of fungal associates, using pyrosequencing analysis of ITS2 region for fungal identification. The investigated species varied with regard to germination, seedling development and diversity of associated fungi during juvenile ontogeny. Results suggest that fungal host specificity increases during juvenile ontogeny, most pronounced in the fully mycoheterotrophic species, but a narrowing of fungal associates was found also in two partially mycoheterotrophic species. We suggest that variation in specificity of associated fungi during seedling ontogeny in mycoheterotrophs represents ongoing evolution along a parasitism-mutualism continuum.

Deficiencies in the health care system contribute to a high rate of late HIV diagnosis in Sweden.

OBJECTIVES: The aim of the study was to identify factors in HIV-infected patients and the health care system which contribute to late diagnosis. METHODS: All patients who were newly diagnosed with HIV infection at 12 clinics in Sweden over a period of 2.5 years (n = 575) were included in the study, corresponding to three-quarters of newly diagnosed HIV infections in the country. The patients were classified as non-late presenters or late presenters (LPs), defined as those with a CD4 count < 350 cells/µL or AIDS. LPs were subdivided into those without and those with advanced HIV disease, which was defined as a CD4 count < 200 cells/µL or AIDS. Demographics, missed AIDS and HIV-associated symptoms in the preceding 3 years, immigration date, and health examination at immigration were recorded. RESULTS: Fifty-eight per cent of the patients were LPs, of whom 66% had advanced disease. Age > 30 years, origin in sub-Saharan Africa or Eastern Europe/Asia/the Pacific region, and country of transmission being in sub-Saharan Africa or unknown were associated with late presentation. Half of the patients of non-Swedish origin had lived for more than 1 year in Sweden at diagnosis and 66% had a missed HIV testing opportunity at immigration. Twenty-seven per cent of all patients had presented for health care with AIDS- and/or HIV-associated conditions without having an HIV test. Sixteen per cent had a history of symptoms without seeking care. CONCLUSIONS: Deficiencies in the health care system with missed HIV testing opportunities contribute to the high proportion of late presenters in Sweden, especially among migrants. With increased testing at immigration and further incorporation of "indicator-guided" testing in general practice, most patients could be diagnosed earlier.

Auditing HIV Testing Rates across Europe: Results from the HIDES 2 Study.

European guidelines recommend the routine offer of an HIV test in patients with a number of AIDS-defining and non-AIDS conditions believed to share an association with HIV; so called indicator conditions (IC). Adherence with this guidance across Europe is not known. We audited HIV testing behaviour in patients accessing care for a number of ICs. Participating centres reviewed the case notes of either 100 patients or of all consecutive patients in one year, presenting for each of the following ICs: tuberculosis, non-Hodgkins lymphoma, anal and cervical cancer, hepatitis B and C and oesophageal candidiasis. Observed HIV-positive rates were applied by region and IC to estimate the number of HIV diagnoses potentially missed. Outcomes examined were: HIV test rate (% of total patients with IC), HIV test accepted (% of tests performed/% of tests offered) and new HIV diagnosis rate (%). There were 49 audits from 23 centres, representing 7037 patients. The median test rate across audits was 72% (IQR 32-97), lowest in Northern Europe (median 44%, IQR 22-68%) and highest in Eastern Europe (median 99%, IQR 86-100). Uptake of testing was close to 100% in all regions. The median HIV+ rate was 0.9% (IQR 0.0-4.9), with 29 audits (60.4%) having an HIV+ rate >0.1%. After adjustment, there were no differences between regions of Europe in the proportion with >0.1% testing positive (global p = 0.14). A total of 113 patients tested HIV+. Applying the observed rates of testing HIV+ within individual ICs and regions to all persons presenting with an IC suggested that 105 diagnoses were potentially missed. Testing rates in well-established HIV ICs remained low across Europe, despite high prevalence rates, reflecting missed opportunities for earlier HIV diagnosis and care. Significant numbers may have had an opportunity for HIV diagnosis if all persons included in IC audits had been tested.

Quality of life in patients with dental conditions: comparing patients' and providers' evaluation.

OBJECTIVE: To measure the agreement between patients and their caregivers in evaluating patients' oral quality of life. BASIC RESEARCH DESIGN: Cross-sectional study. CLINICAL SETTING: Data collected in four Swedish dental clinics in 2004. PARTICIPANTS: Consecutive patients. Data were completed for 444 patients. Fifteen dentists and 12 dental hygienists agreed to participate. INTERVENTIONS: For each patient, the patient him/herself and his/her caregiver completed the 14-item Oral Health Impact Profile (OHIP-14), a specific instrument used to measure quality of life in oral conditions, with higher scores indicating a worse quality of life. Information on personal and clinical characteristics of patients were also collected. MAIN OUTCOME MEASURES: Median OHIP-14 scores given by caregivers and patients were calculated and compared in different subgroups of patients. Cohen's kappa was calculated to measure the agreement between the evaluation of patients and caregivers. RESULTS: OHIP-14 scores median values were 3.0 among patients and 9.0 among caregivers. Caregivers always gave a higher score than patients, especially in older patients and patients with lower education. The concordance between patients' and caregivers' evaluation was very low (for different OHIP-14 cutoffs: Cohen's kappa from 0.10 to 0.15). CONCLUSIONS: In this study, great discrepancies were observed between patients and caregivers in the evaluation of patients' oral quality of life, with caregivers overestimating the burden of dental conditions on patients. It is important to improve patient-caregiver communication, in order to increase patient satisfaction and provide better care. A good patient-caregiver relationship is essential for the patients' well-being and their adherence to treatment.

A multilevel analysis of factors affecting the difference in dental patients' and caregivers' evaluation of oral quality of life.

In a previous study, we observed that the concordance between patients' and caregivers' evaluation of oral health-related quality of life (OHRQoL) was low. The aim of this study was to use multilevel analysis to investigate the possible determinants of the low concordance, taking into account different patients' demographic and clinical variables, the financial system used by patients to pay for dental treatment, and the role of the different caregivers and clinics. The OHRQoL of patients was assessed both by the patients and by their caregivers, using the Oral Health Impact Profile (OHIP)-14. Data were collected in four clinics, and patients were evaluated by one of 27 caregivers. We tested eight multilevel models, using the difference (caregivers OHIP - patients OHIP) as the dependent variable. Data were complete for 432 patients. The mean difference was 4.4 (standard deviation = 8.2; higher scores indicated a higher impact on OHRQoL). The variance due to patients was partly explained by their age, gender, and number of teeth, with a greater OHIP difference for older vs. younger patients, for women than for men, and in patients with fewer teeth. Almost 30% of the variance was due to caregivers, while the effect of clinics was not significant. It is important to study the possible causes of the different judgments concerning patients' OHRQoL by patients and caregivers, in order to improve the patients' satisfaction with care.

Financial systems' impact on dental care; a review of fee-for-service and capitation systems.

OBJECTIVE: This review covers the impact of financial systems on dental care. BACKGROUND: Remuneration in fee-for-service (FFS) is done per service provided and in capitation (CAP) per patient enrolled. It may be expected that dentists' incentive in CAP is to keep the number of services provided at a minimum, while in FFS it is to keep the number of services at a maximum. This should lead to a different impact on care, with the dentists in CAP focusing more on prevention and dentists in FFS more on restorative treatment. Six questions were put: Does CAP increase or decrease caries incidence? Does CAP increase or decrease restorative treatments? Does CAP increase preventive care? Does CAP increase or decrease productivity? Does CAP increase or decrease the dentist's satisfaction with his/her work? Does CAP increase or decrease the patients' satisfaction with the oral care provided? METHODS: Literature was obtained through searches in databases. A format was developed to define the literature of interest. RESULTS: CAP decreases restorative treatment and there is a tendency of decreased caries incidence. "Supervised neglect" cannot be established. CAP increases preventive care. A conclusion regarding productivity was not possible. The results on dentist's satisfaction with work were inconclusive, as were the results regarding patient satisfaction. CONCLUSIONS: CAP has a different impact on provided care than FFS. More research is needed in this area and focus on efficiency is of importance.

Inhibition of cell proliferation and induction of apoptosis by N(1),N(11)-diethylnorspermine-induced polyamine pool reduction.

Reduction of cellular polyamine pools results in inhibition of cell proliferation and sometimes in induction of cell death. Reduction of cellular polyamine pools can be achieved by several strategies involving all the mechanisms of polyamine homoeostasis, i.e. biosynthesis, catabolism and transport across the cell membrane. In the present paper, we concentrate on results achieved using the polyamine analogue DENSPM (N(1),N(11)-diethylnorspermine) on different cell lines. We discuss polyamine levels in DENSPM-treated cells in relation to effects on cell cycle kinetics and induction of apoptosis. To really understand the role of polyamines in cell cycle regulation and apoptosis, we believe it is now time to go through the vast polyamine literature in a meta-analysis-based manner. This short review does not claim to be such a study, but it is our hope to stimulate such studies in the polyamine field. Such work is especially important from the viewpoint of introducing drugs that affect polyamine homoeostasis in the treatment of various diseases such as cancer.

Growth hormone endocrinology of Atlantic salmon (Salmo salar): pituitary gene expression, hormone storage, secretion and plasma levels during parr-smolt transformation.

A number of studies on the Atlantic salmon (Salmo salar), have reported changes in plasma GH during parr-smolt transformation, but there is a lack of information about the endocrinology of the GH system during this process. In order to elucidate the mechanisms underlying these changes in plasma GH levels during the parr-smolt transformation of Atlantic salmon, GH mRNA expression in the pituitary was studied together with total pituitary GH content, in vitro GH secretion rate and plasma GH and IGF-I levels. Atlantic salmon were kept in outside tanks, under natural condition from early February until late June. Approximately three times a month fish were killed and pituitaries and blood were sampled for investigation. Further, pituitaries were moved to the laboratory for in vitro GH secretion studies. The results show that the GH system is first activated by an increase in GH secretion rate, which leads to an increase in plasma GH levels and causes a drop in the total GH content of the pituitary. This drop in pituitary GH content is later reversed by an increased GH synthesis seen as an increase in GH mRNA expression. Maximal activation of the GH system is seen to occur in early May, when plasma IGF-I levels reach highest levels, after which a certain deactivation of the GH system takes place. The data show that plasma levels of GH are to a large extent regulated by the secretion rate from the pituitary, although changes in the GH clearance rate are also likely to take place and influence the plasma GH levels. The study further underlines the significant role that the GH-IGF-I axis plays in the parr-smolt transformation of the Atlantic salmon.

Breast-feeding, pain and infection.

A syndrome of deep pain in the breast during and immediately after lactation has been ascribed to an infection with Candida albicans. A series of 20 patients with deep pain, another 20 with superficial infection and 20 healthy women were compared with respect to the growth of bacteria and fungi. C. albicans was found twice as often in the milk of women with superficial lesions compared to those with deep pain. Bacteria were often found on the nipple and in the milk of those complaining of deep pain. Thus, if the deep pain syndrome is caused by microbes, this study points to a pathogenic role of bacteria rather than fungi.

[Somatostatin receptors. A new way to diagnosis and therapy of neuroendocrine tumors]. / Somatostatinreceptorer. Ny väg till diagnos och terapi av neuroendokrina tumörer.

Verification of the presence of somatostatin receptors on neuroendocrine tumour cells opened up unique diagnostic and therapeutic possibilities. Long-acting somatostatin analogues are currently used to alleviate symptoms of excessive hormone synthesis in patients with such tumours. Radiolabelled somatostatin analogues can be used both for high specificity and high sensitivity scintigraphic localisation of such tumours and for intraoperative scintillation detection. Detailed studies in patients and in tumour cells in vitro have shown 111In-octreotide uptake to be high and retention times long in tumour tissue, and have yielded evidence of intracellular localisation of the radionuclide. These findings thus showed somatostatin receptor-mediated radiotherapy to be a possible treatment alternative after close characterisation of the individual tumour. In the future, it may be possible to use other peptide receptors (e g, growth factor receptors) according to the same principles as applied in the case of somatostatin receptors.

Survival of patients with disseminated midgut carcinoid tumors after aggressive tumor reduction.

Sixty-four consecutive patients with disseminated midgut carcinoids were treated during an 8-year period according to a single clinical protocol aimed at aggressive tumor reduction by surgery alone or with subsequent hepatic artery embolization. All patients had markedly elevated urinary 5-hydroxyindoleacetic acid (5-HIAA) levels (581 +/- 79 micromol/24 h) and hormonal symptoms. Fourteen patients (22%) reached anatomic and biochemical cure by surgery alone. At follow-up, the mean 5-HIAA levels were still normal after 69.0 +/- 6. 2 months; two patients had died from unrelated causes. With the introduction of somatostatin receptor scintigraphy, subclinical disease was diagnosed in 7 of these 14 patients. Forty patients with bilobar hepatic disease underwent embolization in combination with octreotide. In this group, 5-HIAA levels were still reduced by 55% after 71 +/- 11 months of follow-up, and the 5-year survival was 56%, estimated from the total death hazard function. After embolization, two subgroups could be identified with marked differences in their long-term response to treatment. Ten patients were not embolized owing to complicating diseases. The 5-year survival for the entire series was 58%. A significantly increased risk of cardiovascular deaths was seen, which underlines the importance of total survival analysis in a disease with multiple hormonal effects. It is concluded that an active surgical approach must be recommended to patients with the midgut carcinoid syndrome. In patients with bilobar hepatic disease, embolization combined with octreotide treatment markedly reduced the 5-HIAA excretion and suggested a prolonged 5-year survival.

Systemic radionuclide therapy using indium-111-DTPA-D-Phe1-octreotide in midgut carcinoid syndrome.

A 55-yr-old woman with a midgut carcinoid syndrome due to metastatic spread of an ileal tumor to the liver, paraortic and mediastinal lymph nodes and to the skeleton was given systemic radionuclide therapy with 111In-DTPA-D-Phe1-octreotide. Before therapy, dosimetric calculations were performed on whole-body scintigraphs and 111In retention was shown to be long-lasting. Excretion was mainly seen during the first 24 hr after injection; thereafter whole-body retention remained stationary at 30%. Indium-111 activity in tumor biopsies and blood was measured using a gamma counter. Very high tumor-to-blood ratios were obtained: 150 for the primary tumor and 400-650 for liver metastases, which further justified radiation therapy. Indium-111-DTPA-D-Phe1-octreotide treatment was given on three separate occasions (3.0, 3.5 and 3.1 GBq) 8 and 4 wk apart. After each therapy, the patient experienced facial flush and pain over the skeletal lesions followed by symptomatic relief, even though no objective tumor regression was found radiologically after 5 mo. After initiation of octreotide treatment, there was a 14% reduction of the main tumor marker, urinary 5-HIAA. After three subsequent radionuclide therapies, there was a further 31% reduction of 5-HIAA levels. No adverse reactions, other than a slight decrease in leukocyte counts, were seen. The mean absorbed radiation dose after the three treatments was estimated to be about 10-12 Gy in liver metastases and 3-6 Gy in other tumors, depending on the size and location of the metastases. Assuming internalization of 111In into tumor cells and a radiobiological effect from short range Auger and conversion electrons, there might be a therapeutic effect on the tumor.

Isometric muscle strength and muscular endurance in normal persons aged between 17 and 70 years.

Isometric muscle strength was measured in 63 women and 65 men, randomly selected, aged 17-70 years, using Penny & Giles' hand-held dynamometer. Eight muscle groups as well as the hand grip strength were tested bilaterally. The muscular endurance was measured as time to exhaustion in the abductors of the shoulder and the flexors of the hip. Reference values for muscle strength and muscular endurance are given in the age groups 17-18, 20-29, 30-39, 40-49, 50-59 and 60-70 years of age. The mean strength of females was about 65-70% of that of the men, but when the results were related to weight, the differences almost disappeared. Both men and women seem to have the greatest muscle strength at the age of about 17-18. The strength is rather constant up to the age of about 40 years, after which a discrete decline is seen up to about 60, from where the decline is more obvious. Muscular endurance showed great variability between individuals. However, no decrease in endurance was seen in older ages. For both sexes, lower reference limits of endurance, with the methods used, for arm abductors are suggested as being 3 minutes and for hip flexors, 90 seconds.

Induction of basophilic differentiation in the human basophilic cell line KU812.

The potential for differentiation of the human basophilic leukaemia cell line KU812 was examined by means of a panel of physiologic and non-physiologic substances used as inducers. The phenotypic characteristics of non-induced KU812 cells included an immature morphology with scanty cytoplasmic granulation, expression of a low amount of high affinity, but no low affinity receptors (CD 23) for IgE, and a capacity for low-rate histamine synthesis. The differentiation process was characterized by a rapid (24 h) increase in histamine production a slower morphological maturation with the development of Alcian blue stainable granula demonstrable after 72 h. Concomitant with the phenotypic alterations, cell growth was inhibited. Differentiation in KU812 cells was inducible by Ara-C and to some extent by sodium butyrate, but not by dimethyl sulphoxide, retinoic acid, or gamma-interferon. Conditioned medium (CM) from cultured peripheral blood cells from atopic individuals and 18 out of 22 analysed glioma cell lines induced differentiation of the KU812 cells, whereas supernatant from only 1 out of 21 other cell lines, including carcinoma, melanoma, sarcoma, leukaemia, and normal fibroblasts had this activity. CM from the T-leukaemic cell line, Mo, also induced KU812 differentiation. A primary fractionation of the active substance from this cell line by reversed phase chromatography eluted the active substance at a concentration of 42-44% acetonitrile. Our present study has shown that the KU812 may serve as an appropriate model to study differentiation of basophils. In addition, its fast and specific response to biological factors makes it suitable as a biological assay for determination of active factor produced by atopic individuals.

Effects of thyroid stimulating immunoglobulin on function and morphology of xenotransplanted toxic diffuse, toxic nodular and normal thyroid tissue.

In order to examine the properties of human thyroid tissue, toxic diffuse goiter (TDG), toxic nodular goiter (TNG) and normal thyroid tissue were transplanted to nude mice. Starting 3 and 10 weeks after the transplantation the mice were given 14 daily injections of control serum or serum containing thyroid stimulating immunoglobulin (TSI). The uptake and release of 125I were repeatedly measured externally. The uptake and unstimulated release of 125I was lowest in TDG transplants, highest in TNG transplants, and intermediate in transplants of normal thyroid tissue. The findings were similar at both 3 and 10 weeks. Injections of TSI reduced the biological half-time of the tracer in TDG and normal transplants, but had no significant effect on TNG transplants. Light and electron microscopic studies showed that hyperplastic TDG tissue underwent involution after transplantation, whereas TNG and normal thyroid tissue remained unchanged. Injection of TSI reactivated TDG tissue; morphometry showed that the absolute and relative volumes of the follicle cells were more than doubled, with a corresponding decrease in the volume of the follicle lumen, and mitotic figures were common. Similar findings were seen in normal transplants, whereas the effect of TSI on TNG tissue was less pronounced. In summary, our observations show that serum from a patient with Graves' disease stimulated iodine release and induced follicle cell hyperplasia and probably also follicle cell multiplication in transplanted normal and TDG tissue, but had a lesser effect on TNG tissue.

Mouse virulence of Salmonella typhimurium mutants deficient in two major outer membrane proteins.

The role of several outer membrane components as virulence factors is well established. We have now isolated spontaneous mutants and conjugational hybrids of smooth mouse virulent Salmonella typhimurium deficient in two major outer-membrane proteins. The lack of the 34,000- and/or 36,000-dalton proteins was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Mutants and recombinants were then tested for their mouse virulence by intraperitoneal inoculation and were found to be as virulent as the parent strain.