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PubMed1986

Behavioral and neurotransmitter changes in the urease-infused rat: a model of congenital hyperammonemia.

Rats implanted with subcutaneous or intraperitoneal osmotic minipumps infusing 0.8-1.25 IU urease/kg/h develop sustained hyperammonemia (range 137-497 microM, controls 88 +/- 51 microM +/- SD) for 5-7 days. Glutamine levels are also significantly elevated in plasma (677 +/- 166 versus 428 +/- 122 microM) and cerebral cortex (13.2 +/- 9.8 versus 4.7 +/- 2.8 nmol/mg tissue). Neurobehavioral abnormalities include decreased food intake and increased stereotypic activity. Increased serotonin turnover was suggested by elevated levels of tryptophan and 5-hydroxyindoleacetic acid in cerebral cortex, brain stem, and cerebellum of urease-infused compared to sham-operated animals. There were no changes in norepinephrine or gamma aminobutyric acid, and there was no correlation between the degree of hyperammonemia or glutaminemia and brain levels of tryptophan or biogenic amines. Animals receiving a tryptophan-deficient diet had significantly lower levels of tryptophan and 5-hydroxyindoleacetic acid in brain regions compared to animals receiving a normal tryptophan intake, under both control and hyperammonemic conditions. Despite the prevention of increased serotonin flux in hyperammonemic animals receiving a tryptophan-deficient diet, food intake and weight declined and there was increased stereotypic behavior.

Ammonia↗
PubMed2005

A new active vitamin D, ED-71, increases bone mass in osteoporotic patients under vitamin D supplementation: a randomized, double-blind, placebo-controlled clinical trial.

CONTEXT: ED-71 has been shown to increase lumbar bone mineral density (BMD) in osteoporotic subjects. However, vitamin D insufficiency might have influenced the effect of ED-71 on BMD. OBJECTIVE: Our objective was to examine whether ED-71 can increase BMD in osteoporotic patients under vitamin D supplementation. DESIGN, SETTING, AND PATIENTS: We conducted a randomized, double-blind, placebo-controlled clinical trial of 219 osteoporotic patients (49-87 yr of age). INTERVENTIONS: Subjects were randomly assigned to receive placebo or 0.5, 0.75, or 1.0 microg/d ED-71 for 12 months. All the subjects received 200 or 400 IU/d vitamin D(3). MAIN OUTCOME MEASURES: We assessed changes in lumbar and hip BMD and bone turnover markers from baseline. RESULTS: Lumbar BMD increased with ED-71 treatment for 12 months (2.2, 2.6, and 3.1% from baseline and 2.9, 3.4, and 3.8% vs. placebo group in subjects receiving 0.5, 0.75, and 1.0 microg ED-71, respectively). Total hip BMD also increased with 0.75 and 1.0 microg ED-71 (-0.8, 0.6, and 0.9% from baseline and 0.1, 1.5, and 1.8% vs. placebo group in the 0.5, 0.75, and 1.0 microg ED-71 groups, respectively). Bone formation and resorption markers were suppressed by approximately 20% after 12 months of 0.75 and 1.0 microg ED-71 treatment. Transient hypercalcemia over 2.6 mmol/liter occurred in 7, 5, and 23% of subjects in the 0.5, 0.75, and 1.0 microg ED-71 groups, respectively, but none of them developed sustained hypercalcemia. CONCLUSIONS: These results demonstrate that ED-71 treatment at around 0.75 microg/d can effectively and safely increase lumbar and hip BMD in osteoporotic patients with vitamin D supplementation.

Absorptiometry, Photon↗
PubMed1984

Plasma exchange and immunosuppressive drug treatment in the Lambert-Eaton myasthenic syndrome.

We undertook serial clinical and electromyographic muscle action potential (MAP) amplitude assessments in nine patients with the Lambert-Eaton myasthenic syndrome (LEMS) over 0.5 to 2.5 years who received plasma exchange (PE; 5 to 15 exchanges over 4 to 19 days) and immunosuppressive drug (IS) treatment (prednisolone 60 to 100 mg on alternate days, azathioprine 2.5 mg/kg for 0.5 to 2.5 years), and who had no signs of carcinoma at entry. Eight patients responded to PE. The peak MAP response occurred 10 to 15 days post-PE, representing a 2.5-fold mean increase and was significant (p less than 0.01). Two of three patients who developed carcinoma responded initially to IS. Three of six noncarcinoma patients developed sustained clinical and MAP remission after 0.5 to 1 year; the three others, of whom two were intolerant of azathioprine, improved. IS and PE may benefit LEMS patients, but caution is required when carcinoma risk is high.

Action Potentials↗
PubMed1996

Psychogenic status epilepticus induced by a provocative technique.

We report a patient who developed sustained psychogenic seizures after undergoing a provocative technique (PT) for the diagnosis of psychogenic seizures. Because patients are at risk for severe agitation with PT, these diagnostic maneuvers should be used selectively, and the clinician should be prepared to deal with this complication.

Adult↗
PubMed2000

Biomedical research leaders: report on needs, opportunities, difficulties, education and training, and evaluation.

The National Association of Physicians for the Environment (NAPE) has assumed a leadership role in protecting environmental health in recent years. The Committee of Biomedical Research Leaders was convened at the recent NAPE Leadership Conference: Biomedical Research and the Environment held on 1--2 November 1999, at the National Institutes of Health, Bethesda, Maryland. This report summarizes the discussion of the committee and its recommendations. The charge to the committee was to raise and address issues that will promote and sustain environmental health, safety, and energy efficiency within the biomedical community. Leaders from every important research sector (industry laboratories, academic health centers and institutes, hospitals and care facilities, Federal laboratories, and community-based research facilities) were gathered in this committee to discuss issues relevant to promoting environmental health. The conference and this report focus on the themes of environmental stewardship, sustainable development and "best greening practices." Environmental stewardship, an emerging theme within and outside the biomedical community, symbolizes the effort to provide an integrated, synthesized, and concerted effort to protect the health of the environment in both the present and the future. The primary goal established by the committee is to promote environmentally responsible leadership in the biomedical research community. Key outcomes of the committee's discussion and deliberation were a) the need for a central organization to evaluate, promote, and oversee efforts in environmental stewardship; and b) immediate need to facilitate efficient information transfer relevant to protecting the global environment through a database/clearinghouse. Means to fulfill these needs are discussed in this report.

Biomedical Technology↗
PubMed2006

REACH-Meharry community-campus partnership: developing culturally competent health care providers.

An important national health care effort is elimination of racial and ethnic disparities in six specific conditions: infant mortality, cancer screening and management, cardiovascular disease, diabetes, human immunodeficiency virus infection, and child and adult immunizations. To address this concern, several health entities in Nashville, Tennessee responded to a grant initiative from the Centers for Disease Control and Prevention to develop a Racial and Ethnic Approaches to Community Health (REACH) demonstration project. The resulting award is the Nashville REACH 2010 Project, charged to develop sustainable methods to reduce and, in time, eliminate racial and ethnic disparities in cardiovascular disease and diabetes in the North Nashville community, where mortality rates of these diseases are substantially higher than in other parts of the county. As one of its many interests, the project included potential health care providers to receive and disseminate messages about disease prevention and health education. The present paper describes the community-campus partnership between the Nashville REACH 2010 project and the post-baccalaureate program of Meharry Medical College, a partnership that enfolded Meharry's pre-professional health care students into the community-based participatory service research project to increase the awareness and sensitivity of future minority health care providers to issues in minority and poor, underserved populations and to increase potential providers' familiarity with the processes involved in community-based participatory research.

Black or African American↗
PubMed2005

Genetically characterized positive control cell lines derived from residual clinical blood samples.

BACKGROUND: Positive control materials for clinical diagnostic molecular genetic testing are in critically short supply. High-quality DNA that closely resembles DNA isolated from patient specimens can be obtained from Epstein-Barr virus (EBV)-transformed peripheral blood lymphocyte cell lines. Here we report the development of a process to (a) recover residual blood samples with clinically important mutations detected during routine medical care, (b) select samples likely to provide viable lymphocytes for EBV transformation, (c) establish stable cell lines and confirm the reported mutation(s), and (d) validate the cell lines for use as positive controls in clinical molecular genetic testing applications. METHODS: A network of 32 genetic testing laboratories was established to obtain anonymous, residual clinical samples for transformation and to validate resulting cell lines for use as positive controls. Three panel meetings with experts in molecular genetic testing were held to evaluate results and formulate a process that could function in the context of current common practices in molecular diagnostic testing. RESULTS: Thirteen laboratories submitted a total of 113 residual clinical blood samples with mutations for 14 genetic disorders. Forty-one EBV-transformed cell lines were established. Thirty-five individual point and deletion mutations were shown to be stable after 20 population doublings in culture. Thirty-three cell lines were characterized for specific mutations and validated for use as positive controls in clinical diagnostic applications. CONCLUSIONS: A process for producing and validating positive control cell lines from residual clinical blood samples has been developed. Sustainable implementation of the process could help alleviate the current shortage of positive control materials.

Blood Specimen Collection↗
PubMed1988

Cardiac arrhythmias during the combined use of intravenous aminophylline and terbutaline in status asthmaticus.

The purpose of this study was to evaluate prospectively the occurrence of cardiac arrhythmias during the combined therapy with intravenous aminophylline and terbutaline in 29 consecutive patients with status asthmaticus. The 24-hour Holter recordings were performed during continuous intravenous infusions of aminophylline (0.56 +/- 0.20 mg/kg/h) and terbutaline (0.034 +/- 0.014 microgram/kg/min). Serum theophylline concentration was 12.1 +/- 3.8 micrograms/ml and never reached the toxic level (greater than 20 micrograms/ml). Premature ventricular contractions (PVCs) were absent in 35 percent of patients and 48 percent had rare unifocal PVCs (less than 10/h). Only 17 percent of patients (five of 29) exhibited severe ventricular arrhythmias: PVCs greater than 10/h (n = 3), multifocal PVCs (n = 1); and a short run of ventricular tachycardia (n = 1). Serious supraventricular arrhythmias occurred in only 7 percent of patients (two of 29) who developed sustained runs of atrial tachycardia. These arrhythmias were always clinically well tolerated and spontaneously resolved without any antiarrhythmic treatment. We conclude that severe arrhythmias are rarely observed during combined therapy with aminophylline and terbutaline in status asthmaticus.

Adult↗
PubMed1990

Cardiac arrhythmias during theophylline toxicity. A prospective continuous electrocardiographic study.

To examine the effects of theophylline toxicity on cardiac rhythm, patients underwent continuous ambulatory ECG recording during acute theophylline toxicity and recovery. The patients, who were recruited form inpatient wards, intensive care units, and emergency departments of a University Medical Center and a Veterans Administration Medical Center, had serum theophylline concentrations (STC) greater than 30 mg/L. There were 14 men and two women with a mean age of 66 years. Fourteen patients had COPD and developed toxicity following long-term theophylline overmedication. Two patients had asthma and ingested an intentional overdose. The STC at the onset of ECG recording ranged from 23 to 67 mg/L. The principal rhythm was sinus in 15 patients; one patient had atrial fibrillation. Sinus tachycardia (heart rate greater than 100/min) was common, and heart rate fell in proportion to STC as toxicity resolved. Supraventricular ectopic beats (SVEs) were noted in seven patients with multiple runs of SVE being present in four. One patient developed multifocal atrial tachycardia (MAT) during toxicity that resolved spontaneously. During the 11 +/- 8 hours of recording during toxicity (STC greater than 20 mg/L), 80 percent of patients had ventricular premature beats (VPBs), 44 percent had paired VPBs, and 25 percent had ventricular runs. One elderly patient with heart disease developed sustained ventricular tachycardia (VT) when STC = 66 mg/L. No other patient had ventricular ectopy that required intervention. During the 10 +/- 6 hours of recording during the "recovery phase" (STC less than 20 mg/L), all patients with VPBs continued to have ectopy; however, the number of VPBs declined significantly. A follow-up 24-hour ECG recording obtained one week after recovery from toxicity in the patient with sustained VT demonstrated marked reduction in the frequency and complexity of VPBs. Patients with frequent (greater than 10/h) or repetitive VPBs were older (p less than 0.05) than those without complex ectopy. There was a trend (p = 0.07) suggesting patients with underlying heart disease were at risk for having complex ventricular ectopy. We conclude that sinus tachycardia, SVE, and VPBs are common among patients with theophylline toxicity; however, sustained ventricular or supraventricular tachyarrhythmias that require antiarrhythmic therapy are uncommon.

Acute Disease↗
PubMedDate not supplied

Anaerobic waste stabilization ponds: a low-cost contribution to a sustainable wastewater reuse cycle.

Waste stabilization ponds (WSP) have been used extensively all over Europe over the last 50 yr for the treatment of municipal and industrial wastewaters. Models presented in manuals should be used only for guidance, and local experience from pilot and full-scale plants of a particular pond type is extremely valuable. Anaerobic WSP are single-stage, continuous- flow, anaerobic reactors operating at ambient temperatures and low volumetric organic loading as a pretreatment method. This article presents a literature review on the different available operational parameters of anaerobic ponds and examples from full-scale plant performance worldwide. On a wastewater management scheme, involving reuse for agriculture, the zero-energy demand of a waste stabilization pond series for the effective removal of organic and microbiological loading under existing legislation and guidelines will remain a valuable tool for sustainable development.

Bacteria, Anaerobic↗
PubMedDate not supplied

Diseases associated with poor water and sanitation: hazards, prevention, and solutions.

This paper examines one of the most staggering challenges facing the mankind, the challenge to conquer diseases associated with poor water and sanitation. Although rapid strides have been made in the last decade of the last century to provide improved water supply and sanitation, the world is still rampant with diseases. More than 1.1 billion individuals lack access to improved water supply and 2.4 billion lack access to improved sanitation in a world that boasts of human rights and sustainable development. The paper details the various types of diseases associated with water and suggests preventions and solution and also examines international development targets and the number of likely deaths from diseases associated with water. Even if the set targets are met successfully, an estimated 40 to 58 million lives would still be lost by the target year of 2015, while the massive efforts of international agencies and governments would be able to salvage an estimated 15 to 22 million lives. The threat of diseases associated with poor water qualities and services makes a fitting case for world resources, finances, and expertise to be focused and diverted to the Water and Sanitation (WATSAN) sector on an unprecedented scale and at a much higher pace than that envisaged in the targets to avoid the large scale death and misery.

Bacterial Infections↗
PubMed2000

Current management of acromegaly.

Acromegaly, a chronic disease of growth hormone (GH) hypersecretion, is most typically caused by a pituitary adenoma. Early diagnosis is critical for prompt intervention to prevent deleterious effects of prolonged exposure to elevated GH and insulin-like growth factor Type I (IGF-I) levels. Current therapy for acromegaly includes several options: surgery, radiotherapy and pharmacotherapy. Transsphenoidal adenomectomy remains a mainstay of therapy for acromegaly. Cure rates are high in microadenomas, but < 50% in macroadenomas. Conventional and stereotactic procedures for radiation therapy are also effective in decreasing GH levels in acromegalic patients, but they need years to normalise GH hypersecretion and carry with them the risk of hypopituitarism. The major classes of drugs currently used to treat acromegaly are dopamine agonists and analogues of somatostatin. Dopamine agonists bind to the D2 receptor and suppress GH hypersecretion in some patients with acromegaly. Their clinical effectiveness is modest, although promising results have been obtained with two novel compounds, quinagolide and cabergoline, that possess long duration of action. Somatostatin analogues have been shown to improve clinical symptoms of acromegaly, decrease hypersecretion of GH and IGF-I and reduce tumour volume in a clinically significant number of patients. Octreotide is administered by s.c. route several times a day, but the recently developed sustained release formulations (octreotide LAR and SR lanreotide) are administered only every 7-28 days by i.m. injections. The complications associated with somatostatin analogues are small, relative to the benefits. Lastly, compounds with a novel mechanism of action, the GH receptor antagonists, are presently under investigation.

Acromegaly↗
PubMed2002

Migration, remittances, livelihood trajectories, and social resilience.

We argue that all aspects of demographic change, including migration, impact on the social resilience of individuals and communities, as well as on the sustainability of the underlying resource base. Social resilience is the ability to cope with and adapt to environmental and social change mediated through appropriate institutions. We investigate one aspect of the relationship between demographic change, social resilience, and sustainable development in contemporary coastal Vietnam: the effects of migration and remittances on resource-dependent communities in population source areas. We find, using longitudinal data on livelihood sources, that emigration and remittances have offsetting effects on resilience within an evolving social and political context. Emigration is occurring concurrently with, not driving, the expansion of unsustainable coastal aquaculture. Increasing economic inequality also undermines social resilience. At the same time diversification and increasing income levels are beneficial for resilience.

Animals↗
PubMedDate not supplied

A historical perspective and prospects of biomedical research on parasitic diseases.

We all hope that biotechnology will answer some social and economical unavoidable requirements of the modern life. It is necessary to improve agriculture production, food abundance and health quality in a sustainable development. It is indeed a hard task to keep the progress on taking into account the rational use of genetic resources and the conservation of biodiversity. In this context, a historical perspective and prospects of the biomedical research on parasitic diseases is described in a view of three generations of investigators. This work begins with a picture of the scientific progress on biomedical research and human health over the last centuries. This black-and-white picture is painted by dissecting current advancements of molecular biology and modern genetics, which are outlined at the meaning of prospecting achievements in health science for this new millenium.

Animals↗
PubMed2000

Plasma metanephrines: a novel and cost-effective test for pheochromocytoma.

Pheochromocytomas are rare chromaffin cell tumors that nevertheless must be excluded in large numbers of patients who develop sustained or episodic hypertension as well as in many others with suggestive symptoms or with a familial history of pheochromocytoma. Diagnosis of pheochromocytoma depends importantly on biochemical evidence of excess catecholamine production by a tumor. Imperfect sensitivity and specificity of commonly available biochemical tests and the low incidence of the tumor among the tested population mean that considerable time and effort can be expended in confirming or ruling out pheochromocytoma in patients where the tumor is suspected. Measurements of plasma free metanephrines provide a superior test compared to other available tests for diagnosis of pheochromocytoma. In particular, the high sensitivity of plasma free metanephrines means that a normal test result reliably excludes all but the smallest of pheochromocytomas so that no other tests are necessary. Measurements of plasma free metanephrines, when systematically combined with other diagnostic procedures outlined in this review, provide a more efficient, reliable and cost-effective approach for diagnosis of pheochromocytoma than offered by previously available approaches.

Adrenal Gland Neoplasms↗
PubMed2006

Ticks (Acari: Ixodidae) associated with wildlife and vegetation of Haller park along the Kenyan coastline.

This artcile describes the results obtained from a tick survey conducted in Haller park along the Kenyan coastline. The survey aimed at evaluating tick-host associations, assessing tick population density, and providing baseline information for planning future tick control and management in the park. Ticks (2,968) were collected by handpicking from eight species of wildlife and by dragging in 14 selected sites within the park. A considerable proportion of ticks were also collected from leaves, stems, and bark of most dominant trees, namely, Casuarina equisetifolia L. (Forst. and Forst.), Cocos nucifera L., Adansonia digitata L., Musa paradisiaca L., and Azadiracta indica Adr. Juss. Dragging was conducted in sites predominantly occupied by Cynodon dactylon L. (Pers.), Cenchrus ciliaris L., Stenotaphrum dimidiatum L. (Kuntze.) Brongn., and Brachiaria xantholeuca Hack. Ex Schinz Stapf. and Loudetia kagerensis K. Schum. Hutch. Eight tick species were identified, and the collection included Rhipicephalus pravus Dönitz 1910, Rhipicephalus pulchellus Gerstäcker 1873, Hyalomma marginatum rufipes Koch 1844, Amblyomma gemma Dönitz 1910, Amblyomma hebraeum Koch 1844, Amblyomma sparsum Neumann 1899, Amblyomma nuttalli Dönitz 1909, and Boophilus decoloratus Koch 1844. Given that the identified tick species are known to parasitize humans as well as livestock, there exist risks of emergence of zoonotic infections mediated by tick vectors. In the recreational environment of Haller park, where tick vectors share habitats with hosts, there is a need to develop sustainable and effective tick control and management strategies to minimize economic losses that tick infestation may cause.

Animals↗
PubMed2005

Environmental monitoring and ecological risk assessment for pesticide contamination and effects in Lake Pamvotis, northwestern Greece.

Monitoring of pesticide residues in water and sediments was conducted as a basis for subsequent ecotoxicological risk assessment for the shallow eutrophic Lake Pamvotis, northwestern Greece. During a one-year study period, atrazine, desethylatrazine (DEA), simazine, diazinon, malathion, oxamyl, carbofuran, and ethion were detected in water and atrazine, desethylatrazine, diazinon, and s-ethyl dipropylthiocarbamate (EPTC) in sediments, all at ppb concentration level. Temporal variation in pesticide concentrations was observed. Highest residue levels for most pesticides in both water and sediment matrices occurred in the May to July period with the exception of atrazine and DEA, which show highest levels in water during the September to November period. The ecological risk associated with pesticide contamination was assessed using two different methods: The toxic unit method, which provides a first indication of the relative contribution of detected pesticides to the total toxicity and a probabilistic approach, and the inverse method of Van Straalen and Denneman, which is used to quantify the ecological risk. The maximum percentage of the ecological risk was 10.3 and 51.8% for water and 17.2 and 70.6% for sediment, based on acute and chronic level, respectively. These results show that pesticides exert a significant pressure on the aquatic system of Lake Pamvotis, especially for the chronic-effect level. Simple quotient methods should be coupled with higher-tier risk assessment, especially if restoration activities on lake ecosystems are to be undertaken for sustainable development.

Animals↗
PubMed2006

Copper inhibition of soil organic matter decomposition in a seventy-year field exposure.

On a site contaminated decades ago with Cu from a wood treatment facility, we can observe that the decomposition of soil organic matter has been slowed. This represents an exceptional data set, and it allows us to address many challenges faced by regulators and risk assessors who are trying to derive appropriate soil quality criteria. These data are representative of a field study with a very well-equilibrated contamination and allow the derivation of chronic toxicity threshold values for the inhibition of microbial respiration. Soil respiration is the main determinant of the carbon balance, and it is assessed using the accumulation of soil organic matter (SOM) in this case. Using data derived from a 70-year-old field study also has the advantage of not being subject to risk assessment uncertainty factors arising from the potential aging effects of spiked soil or to the uncertainty caused by laboratory-to-field differences, both of which are very difficult to address. The resulting toxicity thresholds for an inhibition of SOM degradation are 154, 193, and 285 mg Cu/kg dry soil for inhibition levels of 10, 20, and 50%, respectively. Setting those thresholds correctly is critical for a proper risk assessment relative to sustainable development and agriculture.

Biodegradation, Environmental↗