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PubMed1985

Programmed ventricular stimulation in survivors of an acute myocardial infarction.

The prognostic significance of programmed ventricular stimulation and its usefulness in relation to other forms of invasive and noninvasive testing was evaluated in 150 survivors of acute myocardial infarction. Ventricular tachyarrhythmias of 6 beats or more were induced in 35 (23%) patients. No significant differences existed between patients with inducible ventricular tachyarrhythmias and those without inducible ventricular tachycardia with respect to occurrence of spontaneous ventricular arrhythmias in the acute and early recovery phase of infarction or predischarge exercise-induced ischemia or arrhythmias, severity of coronary artery disease, or degree of left ventricular dysfunction. A higher incidence of inferior myocardial infarction was observed in patients with inducible ventricular tachycardia when compared with those without inducible ventricular tachycardia (66% vs 41%, p less than .01). During a mean follow-up of 10 +/- 5 months (range 2 to 19), there were two sudden deaths, three nonsudden deaths, and two additional patients developed sustained ventricular tachyarrhythmias. There was no significant difference between patients with and those without inducible ventricular tachyarrhythmias with respect to the occurrence of these events. In this study population, a lower mean ejection fraction (p less than .01), the presence of a ventricular aneurysm (p less than .05), and exercise-induced ventricular premature contractions (p less than .05) were predictors of sudden death and of spontaneous ventricular tachycardia. Thus, the findings of this study do not support the hypothesis that the induction of ventricular tachyarrhythmias in patients recovering from acute myocardial infarction identifies a group at high risk for sudden cardiac death.

Acute Disease↗
PubMed1991

Standards for analysis of ventricular late potentials using high-resolution or signal-averaged electrocardiography. A statement by a Task Force Committee of the European Society of Cardiology, the American Heart Association, and the American College of Cardiology.

Sufficient data are available to recommend the use of the high-resolution or signal-averaged electrocardiogram in patients recovering from myocardial infarction without bundle branch block to help determine their risk for developing sustained ventricular tachyarrhythmias. However, no data are available about the extent to which pharmacological or nonpharmacological interventions in patients with late potentials have an impact on the incidence of sudden cardiac death. Therefore, controlled, prospective studies are required before this issue can be resolved. As refinements in techniques evolve, it is anticipated that the clinical value of high-resolution or signal-averaged electrocardiography will continue to increase.

American Heart Association↗
PubMed1994

Open infarct artery, late potentials, and other prognostic factors in patients after acute myocardial infarction in the thrombolytic era. A prospective trial.

BACKGROUND: Successful reperfusion of the infarct-related artery in patients with acute myocardial infarction has been shown to reduce in-hospital as well as 1-year mortality. Besides the thrombolysis-induced myocardial salvage, there is increasing evidence that an open infarct-related artery results in increased electrical stability of the heart and that this effect is at least in part responsible for the favorable long-term outcome of these patients. The exact incidence of arrhythmic events during the first year after myocardial infarction and the predictive value of different risk factors for these complications, however, have not been determined in patients in the thrombolytic era. METHODS AND RESULTS: A total of 173 patients with acute myocardial infarction, 51% treated with thrombolysis, were prospectively entered into the study. At the time of hospital discharge, signal-averaged ECG, Holter monitoring, radionuclide angiography, coronary angiography, and levocardiography were performed in all patients. An open infarct-related artery was documented in 136 patients. The overall incidence of late potentials was 24% (41 patients). By multivariate analysis, an occluded infarct-related artery (P = .04) and the presence of regional wall motion abnormalities (P = .02) were the strongest independent predictors for the development of a late potential. Residual ischemia was treated by either percutaneous transluminal coronary angioplasty or surgery in 86 of 173 patients (50%). Seventy percent of the patients received beta-blocker therapy. During a mean follow-up of 12 +/- 5 months, 7 patients died suddenly or had ventricular fibrillation documented, while only 2 developed sustained monomorphic ventricular tachycardia. Overall 1-year mortality was 4.1%. Multivariate analysis revealed only an occluded infarct-related artery as an independent predictor of arrhythmic complications (P = .017). CONCLUSIONS: In patients with acute myocardial infarction treated according to contemporary therapeutic guidelines, with a large proportion of individuals undergoing coronary artery revascularization, a low incidence of arrhythmic events, particularly of ventricular tachycardia, was observed in the first year after the index infarction. The presence or absence of an open infarct-related artery was the strongest independent predictor of these events, whereas other traditional risk factors, such as late potentials, were less helpful in identifying patients prone to sudden death. These findings emphasize the importance of the open artery hypothesis in patients recovering from acute myocardial infarction.

Adult↗
PubMed1990

Hypertension in rats induced by renal grafts from renovascular hypertensive donors.

Renal transplantations were performed, using microsurgical techniques, with adult male two-kidney, one clip hypertensive rats (n = 9) and sham-operated normotensive Wistar-Kyoto rats (n = 8) as kidney donors and with F1 hybrids, bred from Wistar-Kyoto and stroke-prone spontaneously hypertensive rat parents, as recipients. Systolic blood pressure before surgery was 200 +/- 2.7 mm Hg in hypertensive and 115 +/- 1.7 mm Hg in normotensive donors and 144 +/- 7.1 and 138 +/- 3.5 mm Hg in the two groups of recipients. Renal hypertension in donors was maintained for 14 weeks before surgery was performed and the nonischemic kidneys were transplanted. Bilaterally nephrectomized recipients of renal grafts from hypertensive donors developed sustained hypertension (185 +/- 3.9 mm Hg). In contrast, in recipients of renal grafts from normotensive donors, blood pressure decreased significantly to the level of the donors (111 +/- 3.7 mm Hg). Posttransplantation hypertension in recipients of renal grafts from hypertensive donors was associated with intrarenal vascular hypertrophy, smaller kidneys, a decreased glomerular filtration rate, an increased plasma urea concentration, and polydipsia as compared with normotensive transplanted controls. Renal pyelograms revealed no gross anatomic alterations of transplanted kidneys. Our data indicate that secondary damage to the renal grafts caused by high perfusion pressure before transplantation can induce hypertension in recipients of these kidneys. Furthermore, our data suggest that renal mechanisms may be necessary to maintain borderline hypertension in F1 hybrids.

Animals↗
PubMed1992

Protein kinase C of smooth muscle.

The primary mechanism of regulation of smooth muscle contraction involves the phosphorylation of myosin catalyzed by Ca2+/calmodulin-dependent myosin light chain kinase. However, additional mechanisms, both Ca(2+)-dependent and Ca(2+)-independent, can modulate the contractile state of smooth muscle. Protein kinase C was first implicated in the regulation of smooth muscle contraction with the observation that phorbol esters induce slowly developing, sustained contractions. Protein kinase C occurs in at least four Ca(2+)-dependent (alpha, beta I, beta II, and gamma) and four Ca(2+)-independent (delta, epsilon, zeta, and eta) isoenzymes. Only the alpha, beta, epsilon, and zeta isoenzymes have been identified in smooth muscle. Both classes of isoenzymes have been implicated in the regulation of smooth muscle contraction. However, the physiologically important protein substrates of protein kinase C have not yet been identified. Specific isoenzymes may be activated by different contractile agonists, and individual isoenzymes exhibit some degree of substrate specificity. Prolonged activation of protein kinase C can result in its proteolysis to the constitutively active catalytic fragment protein kinase M, which would dissociate from the sarcolemma and phosphorylate proteins such as myosin that are inaccessible to membrane-bound protein kinase C. Protein kinase M induces relaxation of demembranated smooth muscle fibers contracted at submaximal Ca2+ concentrations. We suggest that protein kinase C plays two distinct roles in regulating smooth muscle contractility. Stimuli triggering phosphoinositide turnover or phosphatidylcholine hydrolysis induce translocation of protein kinase C (probably specific isoenzymes) to the sarcolemma, phosphorylation of protein, and a slow contraction. Prolonged association of the kinase with the membrane may lead to proteolysis and release into the cytosol of protein kinase M, resulting in myosin phosphorylation and relaxation.

Amino Acid Sequence↗
PubMed1995

Muscle delivery of human kallikrein gene reduces blood pressure in hypertensive rats.

We recently found that transgenic mice expressing human tissue kallikrein develop sustained hypotension. The result suggests that a continuous supply of human tissue kallikrein could have a prolonged effect on blood pressure reduction. In the present study, we investigated the potential of using human tissue kallikrein for gene therapy by injecting a kallikrein gene construct into the skeletal muscle of spontaneously hypertensive rats. Expression of the human tissue kallikrein messenger RNA in spontaneously hypertensive rats was identified by reverse transcription-polymerase chain reaction with Southern blot. Human tissue kallikrein was detected in the injected animals by an enzyme-linked immunosorbent assay. Injection of the human kallikrein gene into spontaneously hypertensive rats caused a significant reduction of systemic blood pressure, ranging from 15 to 26 mm Hg, compared with the control group. The differences were significant 1 week after the injection and continued for more than 2 months. Blood pressure reduction could be reversed after the administration of the bradykinin antagonist Hoe 140. The results indicate that somatic delivery of the human tissue kallikrein gene induces a sustained reduction of systemic blood pressure in spontaneously hypertensive rats. The present study raises the possibility of applying kallikrein gene therapy to the treatment of human hypertensive diseases.

Animals↗
PubMed1994

Distinct receptors and signaling pathways in alpha-thrombin- and thrombin receptor peptide-induced vascular contractions.

The vasoactive mechanisms of the serine protease alpha-thrombin were examined in isolated coronary arteries from dogs. In resting coronary arteries with endothelium, alpha-thrombin caused concentration-dependent contractions that were characterized by an initial transient relaxation followed by slowly developing sustained contractions. The vascular actions of alpha-thrombin were mimicked by the thrombin receptor-activating peptide (TRAP) SFLLRNP, a synthetic peptide based on the cleaved terminus of the thrombin receptor domain. Treatment of the arteries with N omega-nitro-L-arginine or removal of endothelium abolished the transient relaxations and enhanced the contractions, indicating that the transient relaxations were mediated by the concurrent release of endothelium-derived nitric oxide. alpha-Thrombin that had been catalytically inactivated with the irreversible inhibitor by use of D-Phe-Pro-Arg-chloromethyl ketone did not cause contractions, indicating the requirement of proteolytic cleavage by alpha-thrombin to induce contractions. In contrast to TRAP, alpha-thrombin-induced contractions were blocked by hirudin (a specific thrombin inhibitor), nifedipine and diltiazem (Ca2+ channel blockers), or staurosporine and calphostin C (protein kinase C inhibitors). Unlike alpha-thrombin, which undergoes homologous desensitization, TRAP failed to cause desensitization to subsequent stimulation by alpha-thrombin or TRAP. These observations support the hypothesis that vasoactive actions of alpha-thrombin are mediated by a mechanism that involves cleavage at the active site to expose a new NH2 terminus that activates the thrombin receptor. Further, the dissociation between alpha-thrombin and the synthetic receptor peptide in signal transduction and dissimilar desensitizing properties suggest the existence of distinct thrombin receptor subtypes and/or signaling events in vascular smooth muscle.

Animals↗
PubMed2004

Optic nerve damage in mice with a targeted type I collagen mutation.

PURPOSE: Transgenic (Col1a1(r/r)) mice gradually develop elevated intraocular pressure (IOP) with open angles. The present study was undertaken to evaluate optic nerve axonal loss with time in these mice. METHODS: The IOP of transgenic (Col1a1(r/r)) mice and control wild-type (Col1a1(+/+)) mice was measured at 7, 12, 16, 24, 36, and 54 weeks of age using a microneedle method. Transgenic Col1a1(r/r) and control Col1a1(+/+) mice at 24 and 54 weeks of age were randomly selected and their optic nerves were processed conventionally for electron microscopy. Optic nerve cross-sections were collected 300 micro m posterior to the globe. Low (200X) and high (10,000X) magnification images were collected systematically and were masked before analysis. For each nerve, cross-sectional area was measured in low magnification images, and axonal number was counted in high magnification images. RESULTS: Mean IOP of the transgenic Col1a1(r/r) mice was significantly higher than that of the control Col1a1(+/+) mice at 16, 24, 36, and 54 weeks by 21%, 42%, 41%, and 33% respectively (P < 0.05). The mean axonal density and total axonal number in the transgenic Col1a1(r/r) mice at 54 weeks of age (n = 10) was significantly less than those in the control Col1a1(+/+) mice at 24 weeks (n = 5) and 54 weeks (n = 5; P = 0.0081 and P = 0.020, respectively, analysis of variance, P < 0.05 for pair-wise comparisons). The mean axonal density and total axonal number in the transgenic Col1a1(r/r) mice at 54 weeks also were significantly less than in the transgenic Col1a1(r/r) mice at 24 weeks (n = 10). Mean axonal loss between 24 and 54 weeks of age in the transgenic Col1a1(r/r) mice was 28.7%. CONCLUSIONS: Transgenic Col1a1(r/r) mice develop sustained elevation of IOP and progressive optic nerve axon loss. This suggests that these mice may be useful as a mouse model of primary open angle glaucoma as well as for assessing the relationship between collagen type I metabolism and optic nerve axon loss.

Animals↗
PubMed2003

Don't ban PVC: incinerate and recycle it instead!

Plastics are making a growing contribution to sustainable development. For example, over an expected lifetime of 50 years, the use of window frames and insulating materials made of plastic in buildings save many times the energy required to manufacture them. Plastics for packaging purposes provide protection against damage and dirt contamination, thereby saving considerable amounts of material and energy. Choosing appropriate disposal strategies for plastic waste also helps to protect the environment (Mark 2000).

Conservation of Natural Resources↗
PubMed2005

Environmental assessment of supercritical water oxidation and other sewage sludge handling options.

Sustainable development relies on the eco-efficient use of all flows in society; more value created out of each resource unit. Supercritical water oxidation (SCWO) can be used for treatment of wet organic waste. The technology has been under development for over 20 years but has not yet been fully commercialized. SCWO allows for complete oxidation of all organics in sewage sludge and almost complete recovery of the inherent energy, essentially without harmful emissions. In this paper, a life-cycle assessment (LCA) of sewage sludge SCWO (Aqua-Critox) is presented and the results are compared with LCA results for other sludge handling options: agricultural use, co-incineration with municipal solid waste, incineration with subsequent phosphorus extraction (Bio-Con) and sludge fractionation with phosphorus recovery (Cambi-KREPRO). For SCWO, beneficial utilization of the heat of reaction is of crucial importance for the outcome. The electricity consumed by pumping and the nitrous oxide produced are other important parameters. The best sludge handling option from an environmental point of view depends on what aspect is considered more important in the impact assessment. Regarding global warming, the energy recovery methods perform better than agricultural use.

Agriculture↗
PubMedDate not supplied

The Great Lakes Information Network: the region's Internet information service.

Communication is the cornerstone of ecosystem protection and sustainable development efforts in the binational Great Lakes region of North America. Great Lakes environmental protection, remediation, and pollution prevention efforts bring together individuals from across the public sector, business and industry, citizens groups, and academia. The region is now working to enhance communications between these groups and the rest of the world, through the Internet-based Great Lakes Information Network (GLIN). Diverse regional data, information, and human resources located at key agencies and organizations are accessible via GLIN. These online resources span environmental quality, human health effects and other research, resource management, transportation, demographic, and economic data, as well as other resources in the Great Lakes region of the United States and Canada. Federal, state, provincial, and regional agencies and a range of citizen, business, and research organizations are cooperating with the lead agency, the Great Lakes Commission, in developing GLIN into the region's shared Internet resource. GLIN resources are accessible to users of ubiquitous Internet research tools including World Wide Web and Gopher. Statistical information on usage and the region's response to ongoing efforts to build the GLIN system and solicit contributions of data and information indicate that we can continue to build GLIN into a truly regional resource which enhances communication among researchers, policy makers, students, and the general public.

Community-Institutional Relations↗
PubMed2001

Idiopathic trigeminal sensory neuropathy in childhood.

Harris first reported transient idiopathic trigeminal sensory neuropathy in 1935, although it later appeared that, in some of his patients, this condition evolved to typical chronic and painful trigeminal neuralgia. The patients who were later described by Hill and Hughes suffered a combined motor-sensory Vth cranial nerve dysfunction, and most cases reported by Spillane and Wells developed sustained permanent trigeminal neuropathy. The largest reported series of pure trigeminal sensory neuropathy includes 10 adults with varying degrees of sensory disturbance confined to all three nerve divisions. These patients experienced no facial pain or motor deficit, and 5 (50%) recovered completely within a few months. It is estimated that typical trigeminal neuralgia occurs in about 1 in 25,000 of the population and is uncommon prior to the third decade, with 1% of the cases occurring before the age of 20 years. To our knowledge, we present the first clinical report of idiopathic trigeminal sensory neuropathy occurring in childhood.

Administration, Topical↗
PubMed1991

Rice in an interdependent world.

The purpose of this paper is to examine the outcome of the increasing need and dependence on rice as an essential food, and the potential hazards of this trajectory in an interdependent world, and to propose the need for a supranational system to guide decisions made in areas of mutual dependency among nations. All rice producing countries of the world should be responsible for assuring sufficient quantities and qualities of rice for the world's population. However, there are hazards related to emphasis on rice yields associated with the neglect of overall nutritional needs and also the potential for environmental impact given the need for sustainable development. Scientific measurement and data analyses of interdependent supranational variables are needed to guide policies and practices to insure conditions for life will be favorable for people everywhere.

Food Supply↗
PubMed1994

Clinical utility of ambulatory blood pressure monitoring in the evaluation of patients with borderline hypertension.

Blood pressure measured in the physician's office often differ considerably from those recorded during everyday activities away from the medical environment. This fact is particularly important in patients whose office blood pressures are only mildly elevated because, in a large proportion of these people, the elevation is observed only when blood pressures are measured in the physician's office and not when they are measured during normal activities. There is little evidence that this 'white-coat' hypertension is associated with increased cardiovascular risk, but patients with the condition are prone to develop sustained hypertension over time. It is therefore advisable to monitor these individual regularly so that antihypertensive therapy can be initiated when appropriate.

Antihypertensive Agents↗
PubMed2006

Increased endothelin-1 and diminished nitric oxide levels in blister fluids of patients with intermediate cold type complex regional pain syndrome type 1.

BACKGROUND: In complex regional pain syndrome type 1 (CRPS1) pro-inflammatory mediators and vascular changes play an important role in the sustained development and outcome of the disease. The aim of this study was to determine the involvement of vasoactive substances endothelin-1 (ET-1) and nitric oxide (NO) during early chronic CRPS1. METHODS: Included were 29 patients with CRPS 1 who were diagnosed during the acute stage of their disease and observed during follow-up visits. Disease activity and impairment were determined and artificial suction blisters were made on the CRPS1 and the contralateral extremities for measurements of IL-6, TNF-alpha, ET-1 and nitrate/nitrite (NOx). RESULTS: The levels of IL-6, TNF-alpha and ET-1 in blister fluid in the CRPS1 extremity versus the contralateral extremity were significantly increased and correlated with each other, whereas NOx levels were decreased. CONCLUSION: The NOx/ET-1 ratio appears to be disturbed in the intermediate stage of CRPS, resulting in vasoconstriction and consequently in a diminished tissue blood distribution.

Adult↗
PubMed2004

Managing the megacity for global sustainability: the new york metropolitan region as an urban biosphere reserve.

The UNESCO World Network of Biosphere Reserves (WNBR), while not originally conceived to include urban areas, was intended to include sites representing all significant ecosystems with the goal of support for sustainable development locally and globally. Drawing on the example of the New York Metropolitan Region (NYMR), which has a population of 21.4 million, it is argued here that the eventual inclusion of the largest of the world's cities in WNBR not only is within the logic of the biosphere reserve concept, but would also benefit the network and its goals. The ecological significance of the NYMR, its role as a driver for global environmental change, as well as the efforts under way in the city to improve urban environmental management and governance are all examined. Potential added value to the WNBR of including megacities such as the NYMR is considered, in particular, regarding the sharing of best practices, lessons learned, and the strengthening of links between megacities and their global natural resource bases.

City Planning↗
PubMed2004

Selective CD4+ lymphopenia in melanoma patients treated with temozolomide: a toxicity with therapeutic implications.

PURPOSE: Standard schedule temozolomide (TMZ; daily for 5 days every 4 weeks) is often used in melanoma patients, but phase III data show that it is no more effective than standard dacarbazine. Extended TMZ dosing regimens may be superior by delivering the drug continuously at a higher dose over time. Using an extended dosing schedule, we noted a high incidence of lymphopenia and occasional opportunistic infections (OIs). Here we report our retrospective experience in the first 97 patients. MATERIALS AND METHODS: TMZ was administered at 75 mg/m(2)/d orally for 6 weeks every 8 weeks, although nine patients were treated continuously without a break. Seventeen patients were treated with TMZ alone; 73 patients received TMZ with thalidomide; seven patients received TMZ with low-dose interferon alfa. RESULTS: Median duration of TMZ treatment was 113 days; 29% received > or = 24 weeks of therapy. Lymphopenia was seen in 60% of patients (absolute lymphocyte count < 800/microL) with a median of 101 days to lymphopenia. TMZ did not cause significant neutropenia or thrombocytopenia. Lymphopenia was not more common in patients treated concomitantly with thalidomide. In all patients analyzed for lymphocyte subsets, lymphopenia induced by TMZ affected the CD4(+) compartment preferentially. There were two documented OIs (Pneumocystis and Aspergillus pneumonia) as well as other infections indicative of T-cell dysfunction in another 21 patients. CONCLUSION: TMZ at this dose and schedule results in CD4(+) lymphopenia in a majority of patients that can result in OIs. Pneumocystis pneumonia prophylaxis should be considered for patients who develop sustained lymphopenia on TMZ.

Adult↗