Metabolite profiling of obese individuals before and after a one year weight loss program.

OBJECTIVE: We and others have previously characterized changes in circulating metabolite levels following diet-induced weight loss. Our aim was to investigate whether baseline metabolite levels and weight-loss-induced changes in these are predictive of or associated with changes in body mass index (BMI) and metabolic risk traits. METHODS: Serum metabolites were analyzed with gas and liquid chromatography/mass spectrometry in 91 obese individuals at baseline and after participating in a 1 year non-surgical weight loss program.ResultsA total of 137 metabolites were identified and semi-quantified at baseline (BMI 42.7±5.8, mean±s.d.) and at follow-up (BMI 36.3±6.6). Weight-loss-induced modification was observed for levels of 57 metabolites in individuals with ⩾10% weight loss. Lower baseline levels of xylitol was predictive of a greater decrease in BMI (ß=0.06, P<0.01) and ⩾10% weight loss (odds ratio (OR)=0.2, confidence interval (CI)=0.07-0.7, P=0.01). Decreases in levels of isoleucine, leucine, valine and tyrosine were associated with decrease in BMI (ß>0.1, P<0.05) and ⩾10% weight loss (isoleucine: OR=0.08, CI=0.01-0.3, leucine: OR=0.1, CI=0.01-0.6, valine: OR=0.1, CI=0.02-0.5, tyrosine: OR=0.1, CI=0.03-0.6, P<0.02). CONCLUSIONS: Diet-induced weight loss leads to mainly reduced levels of metabolites that are elevated in obese insulin resistant individuals. We identified multiple new associations with metabolic risk factors and validated several previous findings related to weight loss-mediated metabolite changes. Levels of specific metabolites, such as xylitol, may be predictive of the response to non-surgical weight loss already at baseline.

Ergonomics action research I: shifting from hypothesis testing to experiential learning.

This paper presents the case for the need for 'Action Research' (AR) approaches to gain understanding of how ergonomics considerations can best be integrated into the design of new work systems. The AR researchers work collaboratively with other stakeholders to solve a real-world problem: gaining insight into the problem and factors influencing solution building from an embedded position in the development process. This experience is interpreted in terms of available theory and can support further theory development. This non-experimental approach can help provide practical new approaches for integrating ergonomics considerations into real work system design processes. The AR approach suffers from a lack of acceptance by conventionally trained scientists. This paper aims to help overcome this weakness by developing the underlying theory and rationale for using AR approaches in ergonomics research. We propose further development of hybrid approaches which incorporate other evaluation techniques to extend the knowledge gains from AR projects. PRACTITIONER SUMMARY: Researchers should engage directly with organisations in ergonomics projects so that they can better understand the challenges and needs of practitioners who are trying to apply available scientific knowledge in their own unique context. Such 'Action Research' could help develop theory and approaches useful to improve mobilisation and application of ergonomics knowledge in organisations.

Cost effectiveness of cardiac resynchronization therapy in Greece: an analysis based on the CArdiac REsychronization in Heart Failure trial.

AIMS: Health economic considerations have become increasingly important in healthcare. The aim of this study was to investigate the incremental cost effectiveness of cardiac resynchronization therapy (CRT) plus medical therapy compared with medical therapy alone in the Greek health-care system. METHODS AND RESULTS: The health economic analysis was based on the CARE-HF trial, a randomized clinical trial estimating the efficacy of adding CRT (n = 409) to optimal pharmacological treatment (n = 404) in patients with moderate-to-severe heart failure with markers of cardiac dyssynchrony. Health care resource use from CArdiac REsychronization in Heart Failure was combined with costs for CRT implantation and hospitalization from publicly available sources. The analysis was based on a lifetime perspective, with the life expectancy estimated from the clinical trial data. Shorter time horizons were explored in the sensitivity analysis. The cost per quality-adjusted life year (QALY) gained with CRT was €6,045 in Greece, with a 95% confidence interval for the cost-effectiveness ratio of €4,292-9,411 per QALY gained. CONCLUSIONS: The results of the economic evaluation of CRT in Greek health-care setting indicate that it is a cost-effective treatment compared with traditional pharmacological therapy. Cardiac resynchronization therapy can therefore be recommended for routine use in patients with moderate-to-severe heart failure and markers of dyssynchrony.

A role for a new herpes virus (KSHV) in different forms of Kaposi's sarcoma.

Kaposi's sarcoma (KS) is a previously rare, tumour-like lesion of controversial biological nature. KS has since the early 1980s become frequent in patients with AIDS, particularly in homosexuals. KS is also endemic in Central Africa predominantly in otherwise healthy men but also in women and children. Recently, evidence for the presence of novel, herpes virus DNA sequences in more than 90% of AIDS Kaposi lesions (AKS) was presented. This DNA was identified using representational difference analysis (RDA) generating short, unique sequences with variable homology to several herpes virus, but no intact virus was recovered. If these DNA-sequences are also present in other, non-HIV-associated forms of Kaposi's sarcoma this would strongly suggest a specific, aetiopathological involvement of this putative new herpes virus in the pathogenesis of Kaposi's sarcoma, rather than a contamination of yet another opportunistic virus in immunosuppressed AIDS patients.

PIP: Samples were examined by polymerase chain reaction (PCR) for the presence of the putative Kaposi's sarcoma herpes virus (KSHV). KS DNA from HIV-negative, African, endemic (EKS) samples, and epidemic HIV-positive KS (AKS), and sporadic KS (SKS) samples were tested from Tanzania and Sweden. All of the HIV KS (18 African EKS and 4 Swedish SKS) as well as the HIV-positive AIDS-related KS (16 African and 7 Swedish AKS) biopsies were shown to contain the previously described DNA sequences. KS lesions from children, females, and males in various tissues were analyzed including skin, lymph nodes, gut and oral mucosa. All forms of KS showed a single PCR product of the expected size (233 base pairs). To exclude amplification of other types of herpes virus, virus preparations of Epstein-Barr virus (EBV), herpes simplex virus, cytomegalovirus, vesicular stomatitis, and human herpes virus type 6 (HHV6) were assayed, again by PCR, using the KSHV primers. No PCR products were obtained with any of these virus strains. However, most HIV-positive and HIV-negative KS DNA samples also contained either EBV and/or HHV6 sequences. All biopsies from non-KS tissues (cells) of HIV-positive and HIV-negative individuals were consistently negative for KSHV by PCR. The observation that the same herpes virus-like DNA sequence is present in endemic and sporadic, as well as AIDS-related, Kaposi's sarcoma cases suggests a possible pathogenic association between this putative novel, herpes-like virus and KS. The herpes virus-like DNA sequences described by Y. Chang in 1994 may indeed represent a novel herpes (KSHV), etiopathologically associated with various clinical forms of Kaposi's sarcoma. Its pathogenic importance is indicated by its presence in different KS tissues with various clinical types of KS and its absence from non-KS-involved tissues. Furthermore, the presence of KSHV in KS of children suggests a nonsexual mode of transmission.

Expression of both oestrogen receptor alpha and beta in human skeletal muscle tissue.

There are two oestrogen receptors (ERs), ERalpha and ERbeta. ERbeta protein is expressed in human skeletal muscle in the nuclei of both myofibres and endothelial cells, whether ERalpha protein is present in this tissue is unknown. We studied the expression of ERalpha protein in human skeletal muscle biopsies taken from vastus lateralis from four men, four women, two children and two postmenopausal women. Immunohistochemistry was used to determine the proportions of nuclei that were positively stained for ERalpha, the proportion of ERalpha-positive nuclei located in the muscle fibres and in capillaries and to test for possible co-expression of ERalpha and ERbeta. Both ERs were expressed in all subjects. Of all nuclei, 63% stained for ERalpha with no sex difference. ERalpha was localised both in myofibres and in endothelial cells of the capillaries, 25% of the ERalpha-positive nuclei were located in the capillaries. ERalpha and ERbeta were generally expressed in the same nuclei. The present study shows for the first time the expression of ERalpha protein in human skeletal muscle independently of age and sex. These results might improve understanding of the physiological role of oestrogen in human skeletal muscle and raise new questions about activation of ERs in skeletal muscle.

Thrombin generation assay: a useful routine check-up tool in the management of patients with haemophilia?

Severity assessment of patients with haemophilia A (HA) is traditionally based on FVIII activity (FVIII:C). Clinical phenotype of HA patients often differs between individuals with the same FVIII:C determined with clotting and chromogenic assays. The aim of this study was to assess the influence of the FVIII:C on thrombin generation (TG) assay parameters both in vitro and ex-vivo postinfusion plasma. For in-vitro approach, influence of FVIII:C was evaluated on TG parameters in several dilutions of a normal plasma pool with commercial FVIII-depleted-plasma (FVIIIDP) and in others experiments, adding increasing amounts of different commercial FVIII concentrates (Fanhdi, Haemate-P, Hemofil-M and Kogenate Bayer) to FVIIIDP. In a series of 50 postinfusion samples, from HA patients of different severity, we assayed TG and FVIII:C (chromogenic and clotting). In vitro experiments, the 50% of maximum TG peak (TGMP) was achieved using only 5% FVIII:C and the TGMP was obtained with 40% of normal VIII:C. Impaired response compared with normal plasma was found in FVIIIDP using addition of increasing amounts of different commercial FVIII concentrates. An overall good correlation between the two FVIII assays was observed (y = 0.9115x - 0.273, r = 0.975, P < 0.001); TGMP and the Lag-Phase-Time (LPT) provided some discrepant results when compared with the total range of FVIII:C measurements. In contrast, correlations for TGMP, LPT and endogenous thrombin potential were improved in samples restricted to FVIII:C <5%. We conclude that TG parameters tentatively could be a tool to tailor the global haemostatic capacity in haemophilic patients.

Health-economic evaluation of three imaging strategies in patients with suspected colorectal liver metastases: Gd-EOB-DTPA-enhanced MRI vs. extracellular contrast media-enhanced MRI and 3-phase MDCT in Germany, Italy and Sweden.

The purpose of this study was to perform an economic evaluation of hepatocyte-specific Gd-EOB-DTPA enhanced MRI (PV-MRI) compared to extracellular contrast-media-enhanced MRI (ECCM-MRI) and three-phase-MDCT as initial modalities in the work-up of patients with metachronous colorectal liver metastases. The economic evaluation was performed with a decision-tree model designed to estimate all aggregated costs depending on the initial investigation. Probabilities on the need for further imaging to come to a treatment decision were collected through interviews with 13 pairs of each a radiologist and a liver surgeon in Germany, Italy and Sweden. The rate of further imaging needed was 8.6% after initial PV-MRI, 18.5% after ECCM-MRI and 23.5% after MDCT. Considering the cost of all diagnostic work-up, intra-operative treatment changes and unnecessary surgery, a strategy starting with PV-MRI with 959 Euro was cost-saving compared to ECCM-MRI (1,123 Euro) and MDCT (1,044 Euro) in Sweden. In Italy and Germany, PV-MRI was cost-saving compared to ECCM-MRI and had total costs similar to MDCT. In conclusion, our results indicate that PV-MRI can lead to cost savings by improving pre-operative planning and decreasing intra-operative changes. The higher cost of imaging with PV-MRI is offset in such a scenario by lower costs for additional imaging and less intra-operative changes.

An in vitro model for studying neuromuscular transmission in the mouse pharynx.

The muscles of the pharynx are controlled by networks of neurons under the control of specific regions in the brain stem, which have been fairly well studied. However, the transmission between these neurons and the pharyngeal muscles, at the motor end plates, is less well understood. Therefore, an in vitro model for the study of neuromuscular transmission in the pharyngeal muscle of the mouse was developed. Ring preparations from the inferior constrictor and the cricopharyngeus muscles were isolated and mounted for isometric force recording at physiologic temperature. Preparations from the diaphragm and the soleus muscles were examined in parallel. The muscles were stimulated at supramaximal voltage with short tetani at 100 Hz. Following direct stimulation of the muscle fibers, using a longer pulse duration, the rate of force development of the pharyngeal muscles was similar to that of the diaphragm and faster than that of the soleus muscle. By varying the duration of the stimulation pulses, conditions where the nerve-mediated activation contributed to a major extent of the contractile responses were identified. Gallamine completely inhibited the nerve-mediated responses. In separate experiments the dose dependence of gallamine inhibition was examined, showing similar sensitivity in the inferior pharyngeal constrictor compared to the diaphragm and soleus muscles. We conclude that reproducible contractile responses with an identifiable nerve-induced component can be obtained from the mouse inferior pharyngeal constrictor. The pharyngeal muscles have contractile characteristics similar to those of the faster diaphragm. The sensitivity to the neuromuscular blocking agent gallamine of the inferior pharyngeal constrictor was in the same concentration range as that of the diaphragm and soleus muscles.

Cost effectiveness of cardiac resynchronization therapy in the Nordic region: an analysis based on the CARE-HF trial.

BACKGROUND: The aim of this study was to investigate the cost-effectiveness of cardiac resynchronization therapy (CRT) in Denmark, Finland and Sweden. The analysis was based on the CARE-HF trial, a randomised clinical trial investigating the efficacy of adding CRT (n=409) to optimal pharmacological treatment (n=404) in patients with moderate to severe heart failure with markers of cardiac dyssynchrony. The average follow-up time was 29.4 months. METHODS: The health effects were measured in terms of quality-adjusted life years (QALYs) gained. Data on health care resource consumption from CARE-HF was combined with costs for CRT implantation and hospitalisation from university hospitals in Denmark, Finland and Sweden. Calculations were based on patients' expected life time. The expected device lifetime (6 years) was used for CRT, and no additional gains in clinical effects were assumed after the 6 years. RESULTS: The cost-effectiveness ratio per QALY gained was 4800 euros in Denmark, 3600 euros in Finland and 6700 euros in Sweden. The 95% confidence intervals for the cost per QALY gained varied between a lower limit of 1169 euros in Finland to an upper limit of 17,482 euros in Sweden. These values were all below the threshold for being cost-effective in Denmark, Finland and Sweden. CONCLUSIONS: The study indicates that CRT is a cost-effective treatment in Scandinavian health care settings compared to traditional pharmacological therapy and can therefore be recommended for routine use in patients with moderate to severe heart failure and markers of dyssynchrony.

Cost-effectiveness of irbesartan/hydrochlorothiazide in patients with hypertension: an economic evaluation for Sweden.

Irbesartan, an angiotensin-II inhibitor, has been shown to be an effective antihypertensive agent in clinical trials. The purpose of this study was to assess the cost-effectiveness of irbesartan in combination with hydrochlorothiazide (HCTZ) in Swedish health-care setting by predicting clinical events and life years based upon observed reductions in blood pressure in clinical trials. The cost-effectiveness of antihypertensive treatment with irbesartan compared with placebo and to other selected angiotensin-II inhibitors (losartan, valsartan, candesartan) in combination with HCTZ was estimated using a Markov model. The incidence of cardiovascular disease was obtained from the Swedish inpatient registry, whereas the risk reductions associated with antihypertensive therapy were taken from the medical literature. Costs for antihypertensive therapy and for treatment of cardiovascular events were included, and the health effects were measured in terms of quality-adjusted life years (QALYs). The study was conducted from a health-care payer perspective. For a 55-year-old male, irbesartan 150 mg/HCTZ 12.5 mg was a dominant strategy (better health effects at lower costs) when compared with losartan 50 mg/HCTZ 12.5 mg and valsartan 80 mg/HCTZ 12.5 mg, and the cost-effectiveness ratio compared with placebo was 3500 euros per QALY gained. In moderate-to-severe hypertension, irbesartan was cost-effective compared with losartan, whereas the results compared with candesartan were mixed. High-dose combination therapy of irbesartan was also found to be cost-effective compared with low-dose combination therapy. The results from the model indicate that irbesartan provides a cost-effective antihypertensive treatment strategy compared with both placebo, and to valsartan and losartan.

The cost-utility of maintenance treatment with venlafaxine in patients with recurrent major depressive disorder.

AIMS: The Prevention of Recurrent Episodes of Depression with venlafaxine XR for Two Years trial has reported advantages with maintenance treatment for patients with recurrent depressive disorder. The aim of this study was to assess the cost-utility of maintenance treatment with venlafaxine in patients with recurrent major depressive disorder, based on a recent clinical trial. METHODS: A Markov simulation model was constructed to assess the cost-utility of maintenance treatment for 2 years in recurrently depressed patients in Sweden. Risk of relapse and recurrence was based on a recent randomised clinical trial assessing the efficacy and tolerability of maintenance treatment with venlafaxine over 2 years. Costs and quality of life estimations were retrieved from a naturalistic longitudinal observational study conducted in Sweden. Health effects were quantified as quality-adjusted life-years (QALYs). Sensitivity analyses were conducted on key parameters employed in the model. RESULTS: In the base-case analysis, the cost per QALY gained of venlafaxine compared with no treatment was estimated at $18,500 over 2 years. In a probabilistic sensitivity analysis, we found that maintenance treatment with venlafaxine is cost-effective with 90% probability at a willingness to pay per QALY of $67,000 or less. Our long-term analyses also indicate that even under conservative assumptions about future risks of recurrences, maintenance treatment is cost-effective. CONCLUSION: The present study indicates that maintenance treatment for 2 years with venlafaxine is cost-effective in patients with recurrent major depressive disorder.

Resource use and costs associated with patients treated for depression in primary care.

We investigated medical resource consumption, productivity loss and costs associated with patients treated with antidepressants for depression in primary care in Sweden. Patients on treatment for depression were followed naturalistically for six-months, and data on patients' characteristics, daily activity and resource-use were collected. The total cost per patient was estimated at euro 5,500 (95%CI euro 5,000-6,100) over six months in 2005 prices. Direct costs were estimated at euro 1,900 (euro 1,700-2,200), 35% of total costs, and indirect costs at euro 3,600 (euro 3,100-4,100), 65% of total costs. The cost for antidepressants represented only 4% of the total costs. We conclude that the burden of depression is high, both to the individual as well as to wider society, and there seems to be a particular need for therapies that have the potential to improve productivity in depressed patients.

Parallel existence of Epstein-Barr virus (EBV) positive and negative cells in a sporadic case of Burkitt lymphoma.

In the Burkitt lymphoma line Oma-BL1, EBV positive and negative cells coexist. We demonstrate that EBV positive and negative subclones are identical with respect to chromosome markers and HLA type and that the same c-myc rearrangement occurs in all the subclones. This shows that the tumor cells are derived from the same patient and are of monoclonal origin. In the positive subclones, the EBV genome was stably maintained in the episomal form. The EBV negative subclones could be derived from previously uncloned tumor cells in early passage, but not from the EBV positive subclones.

Methodological studies of multiple reference genes as endogenous controls in vascular gene expression studies.

Detection and quantification of differentially expressed genes requires valid and reliable references to control for error variability introduced by preparatory procedures or efficiency of reverse transcription and polymerase chain reaction (PCR) amplification conditions. So-called housekeeping genes are frequently used as endogenous standards, based on the assumption that they are constitutively expressed and independent of experimental conditions. However, if the influence of experimental stimuli is to be analyzed, it cannot a priori be assumed that their expression is unaffected by stimulation. In the present study, the authors studied the expression of different housekeeping genes in the vascular endothelium of intact conduit vessels perfused in a unique biomechanical perfusion model. Ten control gene candidates were investigated by microarray expression analysis. Further, five of these genes were systematically analyzed by real-time reverse transcriptase (RT)-PCR gene quantification and their suitability as reference genes were evaluated. On the basis of these findings, the authors suggest criteria for evaluation of endogenous control genes in vascular perfusion studies.

The cost-effectiveness of candesartan-based antihypertensive treatment for the prevention of nonfatal stroke: results from the Study on COgnition and Prognosis in the Elderly.

Patients who survive a first stroke are often left with permanent disabilities, and have significant needs for rehabilitation and long-term care. Antihypertensive treatment reduces the risk of cardiovascular events such as stroke. The purpose of this study was to investigate the cost-effectiveness of candesartan-based antihypertensive treatment for the prevention of nonfatal stroke. The cost-effectiveness analysis was based on data from Study on COgnition and Prognosis in the Elderly (SCOPE), where patients were randomly assigned to receive the angiotensin receptor blocker candesartan or placebo, with open-label active antihypertensive treatment added as needed. The analysis was carried out using a Markov model, which combined clinical and resource utilization data from SCOPE with Swedish retail prices for drugs and unit costs for in-patient stays, and outpatient visits. The cost per patient was 1949 EUR in the candesartan group and 1578 EUR in the control group. The largest share of the cost was attributed to antihypertensive treatment in the candesartan group and to the long-term cost of stroke in the control group. Candesartan-based antihypertensive treatment was associated with 0.0289 additional quality-adjusted life-years (QALYs) per patient and an incremental cost per QALY gained of approximately 13,000 EUR. Sensitivity analyses showed that these results were fairly stable. In conclusion, the cost per QALY gained with candesartan-based antihypertensive treatment lies within the range of society's willingness to pay for health gains. The results indicate that candesartan-based antihypertensive treatment is cost-effective for the prevention of nonfatal stroke.

Spontaneous activity and stretch-induced contractile differentiation are reduced in vascular smooth muscle of miR-143/145 knockout mice.

AIM: Stretch is essential for maintaining the contractile phenotype of vascular smooth muscle cells, and small non-coding microRNAs are known to be important in this process. Using a Dicer knockout model, we have previously reported that microRNAs are essential for stretch-induced differentiation and regulation of L-type calcium channel expression. The aim of this study was to investigate the importance of the smooth muscle-enriched miR-143/145 microRNA cluster for stretch-induced differentiation of the portal vein. METHODS: Contractile force and depolarization-induced calcium influx were determined in portal veins from wild-type and miR-143/145 knockout mice. Stretch-induced contractile differentiation was investigated by determination of mRNA expression following organ culture for 24 h under longitudinal load by a hanging weight. RESULTS: In the absence of miR-143/145, stretch-induced mRNA expression of contractile markers in the portal vein was reduced. This was associated with decreased amplitude of spontaneous activity and depolarization-induced contractile and intracellular calcium responses, while contractile responses to 5-HT were largely maintained. We found that these effects correlated with a reduced basal expression of the pore-forming subunit of L-type calcium channels and an increased expression of CaMKIIδ and the transcriptional repressor DREAM. CONCLUSION: Our results suggest that the microRNA-143/145 cluster plays a role in maintaining stretch-induced contractile differentiation and calcium signalling in the portal vein. This may have important implications for the use of these microRNAs as therapeutic targets in vascular disease.

Ethanol decreases nocturnal plasma levels of thyrotropin and growth hormone but not those of thyroid hormones or prolactin in man.

Previous studies on the effects of ethanol on circulating pituitary hormones have been carried out mostly during daytime when the secretion of these hormones is generally at a nadir. Therefore, we studied the effects of ethanol on the nocturnal secretion of GH, PRL, TSH, and thyroid hormones (protocol I, nine healthy subjects, five women) and on the TSH and PRL responses to synthetic TRH (protocol II, healthy subjects, four women). Ethanol was given in doses of 0, 0.5 or 1.0 g/kg of BW(protocol I) and 0 or 1.0 g/kg (protocol II) and ingested po at 1900-1945 h. In protocol I, plasma GH rose from 0.6 +/- 0.2 microgram/L (mean +/- SE) at 2200 h to 25.0 +/- 4.3 micrograms/L at 0100 h in control subjects and was almost completely inhibited at 4.5 +/- 1.7 micrograms/L at 0100 h in subjects receiving 1.0 g/kg ethanol (P < 0.01). In subjects receiving 0.5 g/kg ethanol, the inhibition was also significant (P < 0.01), plasma GH being 8.2 +/- 2.5 micrograms/L at 0100 h. Plasma GHRH was measured after solid phase separation in RIA, but it did not show any ethanol-related changes. Plasma PRL exhibited a clear diurnal rhythm in control subjects and rose from 77 +/- 16 at 1800 h to 248 +/- 62 micrograms/L at 0700 h (P < 0.01). The plasma PRL profile was not affected by ethanol. Plasma TSH was 1.4 +/- 0.2 mU/L at 1800-2200 h and rose to 2.3-2.4 mU/L for 0100-0700 h (P < 0.001) in the control subjects. Ethanol 1.0 g/kg suppressed plasma TSH to 1.4 +/- 0.2 mU/L (P < 0.05 at 0100 h and P < 0.01 at 0200 h). According to the area under the curve analyses, the suppression in the nocturnal TSH was 32% in the 0.5 g/kg group and 45% in the 1.0 g/kg group (P < 0.05 for both cases). Circulating free or total T3 and T4 did not show any statistically significant changes that could explain the ethanol-induced inhibition in the nocturnal TSH peak. In protocol II, synthetic TRH (1 microgram/kg BW) was given intravenously, and blood samples were collected before, at 20 and 60 min. TRH significantly stimulated plasma TSH and PRL, but ethanol (1.0 g/kg BW) had no effect on these responses. In conclusion, small amounts of ethanol have unexpectedly great effects on nocturnal surges of TSH, and especially on those of GH, that are apparently mediated by suprapituitary mechanisms. On the other hand, ethanol did not affect the nocturnal PRL surge. These inhibitory effects of ethanol may have unfavorable effects on growth and metabolism in adolescent drinkers.

Comparative absorption of calcium from carbonate tablets, lactogluconate/carbonate effervescent tablet, and chloride solution.

Intestinal absorption of calcium from three different labelled calcium preparations (all containing 500 mg elemental calcium) was determined using the whole body retention and urinary excretion of 47Ca in 14 normal subjects. Chewable calcium carbonate tablets showed a significantly (p less than 0.05) better mean minimum absorption of calcium (25.6% in exp. I, 22.8% in exp. II) than calcium given in the form of a lactogluconate/carbonate effervescent tablet, (17%), but similar to calcium in a chloride solution (24.7%). The minimum calcium absorption varied from 85 to 128 mg. All the preparations were taken with standardized low calcium test meals.

Closed-line integral optimization edge detection algorithm and its application in equilibrium radionuclide angiocardiography.

UNLABELLED: Automatic evaluation of left ventricular (LV) function using equilibrium radionuclide angiocardiography requires an edge detection algorithm to correct and reproducibly delineate the left ventricle. Available algorithms, usually based on differentiation of a radial profile, generally suffer from low precision due to low signal-to-noise ratios and overlapping structures, for example, the left atrium. METHODS: An edge detection algorithm was developed based on the assumption that the LV border can be defined as the maximum, normalized, closed-line integral of a closed curve in a vector field derived by image differentiation. It is further assumed that the closed curve can be described by a Fourier expansion with a limited number of harmonics. Regions of interest (ROIs) generated by this algorithm were compared with ROIs generated by an algorithm based on a combination of thresholding and second-order derivatives. RESULTS: This algorithm delineates the left ventricle and gives results more closely related to ROIs generated manually than the algorithm combining thresholding and the second-order derivative. Our algorithm can also handle the problem of overlapping structures, as demonstrated in phantom simulations. CONCLUSION: The concept of a maximum, normalized closed-line integral will improve the delineation of the LV in an equilibrium radionuclide angiocardiography study. The problem of overlapping structures is overcome by this algorithm because it takes into consideration global edge information.

Malignant lymphoma associated with human AIDS and with SIV-induced immunodeficiency in macaques.

Malignant lymphomas associated with human (HIV) and simian (SIV) immunodeficiency virus infections are reviewed and compared. Recent observation of a high frequency of lymphomas in a series of cynomolgus macaques, highly immunodeficient after infection with SIVsm(smm3) are described. In addition to the increased frequency in human and monkey AIDS, SIV and HIV lymphomas share several important features. Clinically and by histology they present as aggressive high-grade malignant tumors with a predilection for extranodal growth in viscera, skin, central nervous system, testis, and retroorbitally. Most malignant lymphomas are of B-cell origin. AIDS lymphomas in humans are heterogeneous with regard to Epstein-Barr virus (EBV) association. Similarly, most lymphomas in monkeys experimentally infected with SIV tested to date were shown to be associated with an EBV-like simian herpes virus. These observations point to the possibility of using SIV-immunodeficient macaques for study of EBV and other oncogenic and immunosuppressive factors in AIDS-associated lymphomagenesis.