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At least 1,063 records · Page 59Linked to original sources
PubMed1996

Studies on the synthesis and structure-activity relationships of 2-(2-functionalized pyrrolidin-4-ylthio)-1 beta-methylcarbapenems.

A series of new carbapenem derivatives, which have a pyrrolidin-4-ylthio group substituted with a hydroxyalkyl or carbamoyl group at the 2' position as the C-2 side chain, have been prepared. The antibacterial activity and the stability to renal dehydropeptidase-I of these compounds were investigated, and the structure-activity relationships were studied. Among these new carbapenems, (1R,5S,6S)-2-[(2S,4S)-2-¿(2-hydroxy)ethylmercaptomethyl¿pyrroli din-4 -ylthio]-6-[(1R)-I-hydroxyethyl]-1-methyl-1-carbapen-2-em-3- carboxylic acid (1a) showed the most potent and well balanced activity and was selected as a candidate for further evaluation.

Animals↗
PubMed1996

[Research and development of zonisamide, a new type of antiepileptic drug].

Zonisamide (1,2-benzisoxazole-3-methanesulfonamide, AD-810) is a broad spectrum antiepileptic drug which has been launched in Japan and South Korea. It lacks the ureide structure included in most of the existing antiepileptic drugs. Zonisamide was synthesized by the sulfonation and the successive amination of 1,2-benzisoxazole-3-acetic acid in a very poor yield. After several efforts to optimize the compound, zonisamide was selected based on the balance of the efficacy and safety. The yield was greatly improved by the development of new synthetic routes. Zonisamide suppressed maximal electroshock seizures in mice, rats, rabbits and dogs. Its therapeutic plasma concentration range between anticonvulsant and neurotoxic effects was much wider than that of the existing antiepileptic drugs. In electroencephalographic studies on animal models of epilepsy, zonisamide, like phenytoin and carbamazepine, restricted the spread or propagation of seizures and, like sodium valproate, it suppressed the epileptogenic focus activity. Zonisamide was effective in several kindling models. In clinical studies, zonisamide exerted the efficacy against partial seizures (simple, complex, secondarily generalized seizures) and some generalized seizures (tonic-clonic, tonic, atypical absence seizures) that were comparable to that of carbamazepine and sodium valproate, respectively. Zonisamide was also effective in monotherapy. The adverse effects related with zonisamide were mainly drowsiness, ataxia, loss of appetite and gastrointestinal symptoms. Serious adverse effects which may be life-threatening have not been reported.

Animals↗
PubMedDate not supplied

Balancing efficiency, cost-effectiveness and patient choice in opioid selection.

Recent UK government initiatives have stressed the importance of patient choice in health care. In relation to palliative care, this involves the achievement of the best quality of life, respect for patient autonomy and choice over treatment options. Regarding selection of analgesic, the treatment options are evaluated by considering efficacy and potency, routes of delivery, titration and conversion, adverse effects and cost effectiveness. This article explores these issues in relation to the rationale for choice of strong opioids. Morphine and diamorphine are usually considered the most effective, 'first-line' analgesics but is this necessarily the case when patient choice is put into the equation? There is a case for more flexibility in selecting the opioid depending upon individual circumstances. Opioid selection should take into account quality of life issues. However the scope for opioid selection seems likely to be restricted by considerations of cost effectiveness. The challenge is to ensure that the patient voice is heard.

Analgesics, Opioid↗
PubMed1983

Age, sex, and body composition as predictors of children's performance on basic motor abilities and health-related fitness items.

The purpose of this study was to determine the contribution of age, sex, and body composition to children's motor performances on selected basic motor tasks, balance, speed, agility, power, coordination, and reaction time, and health-related fitness items, flexibility, muscle strength and endurance, and cardiovascular functions. 80 subjects were students in Grades 1, 2, 3. Data were submitted to a step-wise multiple linear regression for each criterion variable. Predictor variables were age, sex, and body composition. Age was a significant factor in predicting performance on all variables except muscle strength, endurance, and flexibility. Sex significantly predicted performance for only flexibility and cardiovascular function and body composition for the power and cardiovascular function variables. Beyond the biological potential of each individual are factors that influence his motor development. These factors need early identification to make possible opportunities for each person to reach the full perimeters of motor potential.

Age Factors↗
PubMed1991

Simplified calculation of the NRC estimates for net energy for maintenance in beef cattle diets.

Calculation of dietary intake for beef cattle using the equation outlined by the NRC (1984) is confounded by the need to know the net energy for maintenance content of the diet (NEmkg). Intake cannot be calculated until NEmkg is specified, but intake must be indicated before performance can be predicted. To calculate NEmkg, dietary intake must be known or estimated, or it can be calculated using a complicated quartic equation. This quartic equation, when solved, gives the percentages of selected feedstuffs necessary to balance a diet. Placing the resulting percentages of feedstuffs necessary back into the generalized net energy equation solves for NEmkg. The quartic equation may be simplified by inserting imaginary nutrient values that optimize the equation for simplicity. It remains a quartic equation, but the coefficients for the first three factors of the equation are fixed, with only the unary X term and the coefficient containing variables. A modified version of Newton's method of approximating roots of equations estimates the percentage of feed necessary and when incorporated into the generalized net energy equation solves for NEmkg. The final reduced form results in simplified equations for NEmkg for each of the classes of beef cattle that are easily solved by the hand-held calculator.

Animal Feed↗
PubMed1996

A novel 1 beta-methylcarbapenem antibiotic, S-4661. Synthesis and structure-activity relationships of 2-(5-substituted pyrrolidin-3-ylthio)-1 beta-methylcarbapenems.

The synthesis and biological activity of (1R,5S,6S)-2-[(3S,5S)-5-substituted pyrrolidin-3-ylthio]-6-[(1R)-1-hydroxyethyl]-1- methylcarbapen-2-em-3-carboxylic acids are described. These compounds exhibit potent antibacterial activity against a wide range of both Gram-positive and Gram-negative bacteria including Pseudomonas aeruginosa. Of these new carbapenems, (1R,5S,6S)-2-[(3S,5S)-5-sulfamoylaminomethyl pyrrolidin-3-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarb apen- 2-em-3-carboxyli c acid (S-4661) showed the most potent and well balanced activity and was selected as a candidate for further evaluation.

Anti-Bacterial Agents↗
PubMed1976

[Considerations on graduate education of sanitary engineering in Latin America].

The author reviews the profound process of change in Latin America which presents serious problems for environmental engineering and, consequently, for education in the various disciplines that comprise this specialization. The explosive growth of knowledge and the increase responsibilities of professionals place extreme pressure on engineering schools. These schools are forced to consider curricular changes as well as changes in admission policies and in the image and the service which they should present to society. At the present time, 25 engineering schools offer an "option" of sanitary engineering and 12 schools offer graduate courses for an M.A. in environmental engineering. In the schools themselves, a combination of fulltime and part-time professors prevails. Graduate teaching programs are expected to provide: a) increasingly complex, new scientific and technologic knowledge, b) duly selected disciplines; and c) balanced management techniques. Certain plans of action may be considered. Among these are increasing the number of schools that offer graduate courses, revising curricula, encouraging higher enrollment, including research as a standard element in teaching and, in general, seeking higher standards of excellent. Prospects for the future seem to indicate that the following actions should be taken: 1) increasing interdisciplinary programs; 2) making use of the potential offered by continuing education; and 3) encouraging the development of doctoral studies.

Curriculum↗
PubMed1988

Who wants to be a resident mother?

A survey was conducted to enquire into the attitudes and experiences of mothers staying with their ill children in a teaching hospital. Ninety-four were interviewed informally on the ward and subsequently completed two psychological questionnaires, the Hospital Anxiety and Depression scale concerning themselves and the Rutter A scale concerning their child. Cases were selected by age to balance the groups with resident and non-resident parents. Forty-one mothers stayed on the ward, 19 in a separate parents' house and 34 were not resident. Significant factors affecting a mother's decision to stay were the distance from home and the severity of the illness. Social variables were similar for both groups. No association was found between psychological distress in mother or child and the mother's choice. Experiences on the ward are discussed together with the benefits provided by a purpose built house for resident parents.

Anxiety↗
PubMed2001

[Progress in rehabilitation of dizziness and equilibrium disorders].

Physiopathological basics of vestibular rehabilitation are based on mechanisms of vestibular compensation. In the course of vestibular organ lesion compensation can be achieved sooner through increased activity of the patient in habituation process, with active contribution of the vision and proprioceptive organs. The criteria of qualification and preparation of the patients were presented. The role of creation of adequate motivation of the subject in the process of preparation was emphasised. The progresses that had been achieved in this treatment method were mentioned. The value of individual training programs, that is programs adapted to definite needs of the patients, was appreciated in recent years. It was revealed, that training programs directed to train certain system such as lower limbs strength, failure of vestibular receptor, gait disturbances bring significant improvement in such cases. However traditional exercises consisting in the whole body movements do not bring desirable effects in certain cases. The new methods of assessment of rehabilitation progress were presented. Those methods are based on receding of subjective symptoms during normal daily activities.

Diagnosis, Differential↗
PubMed2001

[Cost-effectiveness of PET in the management algorithms of lung tumors: comparison of health economic data].

Modelling is an accepted, valid and often necessary method for assessing economic effectiveness in terms of cost per life year gained. Comparing an alternative strategy (a) with a baseline strategy (bl), the incremental cost (COSTa-COSTbl) divided by the incremental life expectancy (LEa-LEbl) defines the incremental cost-effectiveness ratio (ICER). Taking watchful waiting as the low-cost baseline strategy for the management of solitary pulmonary nodules, the ICER of positron emission tomography (PET) [3218 euros (EUR) per life year saved (LYS)] was more favourable than that of exploratory surgery (4210 EUR/LYS) or that of transthoracic needle biopsy (6120 EUR/LYS). Changing the baseline strategy to exploratory surgery, the use of PET led to cost savings and additional life expectancy in case of an intermediate pretest probability of malignancy. For management of potentially operable non-small cell lung cancer the use of PET in patients with normalisized mediastinal lymph nodes on CT was most cost-effective (143 EUR/LYS), and the costs of PET were almost balanced by a better selection of patients for beneficial cancer resection. Using PET in patients with enlarged lymph nodes on CT, the ICER raised to 36,667 EUR/LYS. When PET or CT were positive for mediastinal lymph nodes, the exclusion from biopsy confirmation led to cost savings that did not justify the expected reduction in life expectancy. Economic data from the USA and Japan also demonstrated the cost-effectiveness of PET-based algorithms for the management of lung tumours.

Algorithms↗
PubMed1992

Myocardial infarction and baroreflex sensitivity. Clinical studies.

Based on solid experimental evidence the concept has emerged that analysis of autonomic reflexes, and specifically of baroreceptive reflexes, might contribute to the identification of high risk subgroups in the post myocardial infarction phase. Accordingly, we brought this concept to clinical fruition and have performed the first clinical study to investigate the potential prognostic value of baroreflex sensitivity. The present article reviews those clinical results which indicate an almost 15 times greater risk for cardiac mortality among the patients with depressed baroreflex sensitivity. Baroreflex sensitivity has also been correlated with heart rate variability and it was found that the degree of correlation is relatively weak and such that it is not possible to predict one measure from the other. Thus, these two autonomic markers are not redundant. Among the various possibilities to induce favorable alterations in the autonomic balance, our group has selected and analyzed exercise training and the chronic administration of beta-blocking agents. Exercise training, examined in a case-control study involving 70 patients, was found to increase baroreflex sensitivity by 30%. Beta-blockers were found to augment baroreflex sensitivity in 40% of the patients tested. As a logical evolution of these studies we have initiated a large prospective collaborative study destined to enroll 1200 post myocardial infarction patients and to assess the prognostic value of baroreflex sensitivity, of heart rate variability, and of traditional markers such as left ventricular ejection fraction and late potentials.

Clinical Trials as Topic↗
PubMedDate not supplied

Long-term outcome in PD morbidity and mortality.

Two main dialysis modalities exist to treat chronic uremic patients: hemodialysis (HD) and peritoneal dialysis (PD); the latter is used less extensively than the former, but its penetration greatly differs among countries and among different regions of the same country. The comparison of the outcome in PD and HD is not easy, since many factors (mainly criteria for patient selection) oppose an adequate balance of the many factors influencing the patient's outcome. After the very different results in favor of HD in the early '80s, the difference in patient survival between PD and HD is progressively reduced and, in the '90s, many studies have shown comparable results. As far as the cardiovascular system is concerned, PD has some advantages versus HD due to stability in blood volume and electrolyte concentration, and lack of hyperkinetic circulation due to artero-venous fistula. However, this does not positively affect cardiovascular mortality whose prevalence is similar between the two modalities. Factors suggested to explain this unexpected result, namely: some degree of thrombophilia in PD, greater lipid metabolism derangement, and chronic fluid overload. Probably for these reasons, the de novo appearance of cardiovascular disease is similar in both modalities. Technique success is definitely worse in PD in nearly all the papers published. Many improvements in peritoneal solution biocompatibility have been made during the late '90s, but their effects on long-term outcome have to be defined.

Humans↗
PubMed2005

Antioxidant status in children with homozygous thalassemia.

The status of enzymatic and non-enzymatic anti-oxidants was evaluated in 41 patients with transfusion dependent beta-thalassemia. An additional 20 age-matched children, with non-hemolytic anemia, served as controls. Fresh blood samples, obtained in the morning, were processed immediately. Plasma was stored at -80 degrees C. Levels of vitamins A and E were assayed simultaneously by HPLC. RBC vitamin A was not measurable in 29 (70.7%) thalassemics and in all the controls. Plasma vitamin A levels were lower in thalassemics than in controls (p<0.05). Vitamin E in RBCs was not measurable in 13 (31. 7%) cases. The mean level of RBC vitamin E was 3 times lower in thalassemics. Similarly, SOD enzyme activity in thalassemics, was at least 1.5 lower in comparison to the activity documented in controls (p<0. 05). The observations indicate that thalassemics have enhanced oxidative stress. Administration of selective antioxidants and a balanced diet may preclude oxidative damage.

Child↗
PubMed1989

Vitamin C and oral health.

Maintaining natural dentition is a realistic goal given today's improved caries control and attention to good oral hygiene. Expanding knowledge in the area of periodontal diseases provides further insight into health promotion practices which can be effective in preventing tooth loss. Vitamin C's role in maintaining the health of teeth and gingivae remains unchallenged. Now clinical evidence indicates that vitamin C functions in improving host defence mechanisms and is thereby implicated in preserving periodontal health. Common sense tells us that the monitoring of the vitamin C status of individuals, especially those at high risk (e.g., diabetics, smokers, elderly, etc.) for inadequate intakes, will yield positive results for periodontal health. Patient education programs that stress the importance of good nutrition, while at the same time providing practical information for the selection of a well balanced diet, are simple measures that will benefit many.

Ascorbic Acid↗
PubMed1988

Current therapy of acute heart failure.

Acute heart failure involves various pathophysiological mechanisms among which primary reduction of myocardial contractility due to acute myocardial infarction, cardiomyopathy, and after open heart surgery are the most common. Therapy should be as causally related as possible. In patients with mechanical defects such as rupture of the interventricular septum or acute mitral regurgitation due to papillary muscle rupture, surgical correction is mandatory. Systemic hemodynamics can often be temporarily stabilized by mechanical circulatory assist devices until spontaneous recovery has occurred or definitive treatment is possible. The objectives of medical therapy are to relieve pulmonary congestion and to provide adequate systemic tissue perfusion. This is achieved by carefully balancing and monitoring a selection of pharmacological approaches according to each patient's hemodynamic profile. Ventricular filling pressure may be reduced by potent loop diuretics and venous dilating drugs with preservation of an optimal pressure range of 15-18 mmHg; cardiac output can be increased by afterload reduction and/or positive inotropic drugs; preservation of systemic perfusion pressure may necessitate use of arteriolar constrictor therapy. Most of these hemodynamic objectives are met by agents with combined vasodilatory and inotropic effects, e.g., dobutamine and amrinone. Whilst both agents are equally effective at improving pump performance, amrinone, unlike dobutamine, has the advantage of doing so without increasing myocardial oxygen consumption and without tolerance development or significant arrhythmogenicity.

Acute Disease↗
PubMed1982

Evaluation of antacid suspensions containing aluminum hydroxide and magnesium hydroxide.

Liquid antacid suspensions containing aluminum hydroxide and magnesium hydroxide were evaluated for composition, antacid properties, and product quality. The equivalent aluminum oxide and magnesium hydroxide content was determined by chelatometric titration, and sodium content was determined by flame photometry. Antacid properties measured were acid-consuming capacity, antacid effectiveness (preliminary antacid test, acid-neutralizing capacity test), and pH-stat titration. Content uniformity, consistency of the antacid properties, and microbiological content were examined for each product. Data are presented for 36 products for which samples from four or more lots were obtained. The ratio of percentage of equivalent aluminum oxide to percentage of magnesium hydroxide ranged from 1:0.6 to 1:3.5; this range allows for selection of the desired balance between the laxative effect of magnesium hydroxide and the constipating effect of aluminum hydroxide. Based on a daily dose of 280 meq of antacid, the sodium content of the products tested ranged from less than 2% to approximately 45% of the 500 mg per day of sodium allowed in a sodium-restricted diet. The concept of bioavailability was related to the amount of the antacid reacting at pH 3, 37 degrees C during the estimated gastric residence time of 15 minutes. Antacid suspensions are available which will react almost completely (neutralizing greater than 90% of the theoretical quantity of acid) during the estimated gastric residence time. Approximately 4% of the samples contained unacceptable numbers of bacteria. An antacid suspension cannot be adequately evaluated by a single test; choice of a product should be based on an evaluation that integrates several characteristics including sodium content, time and volume required to neutralize a given amount of acid, and uniformity of content.

Aluminum Hydroxide↗