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PubMedDate not supplied

Biochemical mechanisms involved in the hepatotoxicity of some drugs.

To find out the biochemical mechanisms involved in the hepatotoxicity of certain drugs, the continuous evolution of some related biochemical parameters was investigated. The results obtained showed the decrease of cytochrome P450, glutathione (GSH) and aniline hydroxylase, as well as increases of lipid peroxides and tryptophan oxygenase 2 hours after i.p. administration of carbon tetrachloride (CCl4) and paracetamol. Characteristic changes of hepatotoxicity such as increase of blood glutamate-pyruvate transaminase (GPT) and triglycerides, and decrease of free sulfhydryl (SH) groups were observed 24 hours after drug administration. The peroxidation of microsomal lipids appears to be the biochemical mechanism involved in the acute administration of these drugs. Subsequently this peroxidation leads to morphologic hepatic changes. In our experimental conditions, hepatotoxicity was prevented by concomitant administration of cystamine.

Acetaminophen↗

PubMed1982

Retinal breaks without detachment: natural history, management and long term follow-up.

A group of patients with retinal breaks without detachment were analyzed. They were divided into a treatment and a nontreatment group. The treatment group consisted of cases that the authors felt to be at high risk for the development of retinal detachment. Most of these were cases of horseshoe tears following the onset of an acute posterior vitreous detachment. Although a number of modalities were used in the treatment, a transconjunctival cryotherapy approach with topical anesthetic drops is currently used and was the most frequently employed. It is of note that while no case in this series developed a detachment because of inadequate treatment of the original tear a certain number did develop new tears and detachments. This would speak for a frequent follow-up, especially within the first three months following treatment, to anticipate such an occurrence. In the untreated group there were essentially two types of patients. One was the asymptomatic patient in which a retinal tear was found on routine examination and the other was the symptomatic patient with a round hole with pulled out operculum. New tears and or detachments also occurred in the asymptomatic group (4 of 72 eyes) but none of the round holes with pulled out opercula detached. Complications of treatment were related to the anesthesia and included vasovagal reactions and retrobulbar hemorrhage. One case seen in consultation had evidence of scleral perforation from a bridle suture and illustrates the inherent danger in any ophthalmic ocular procedure. The question of macular pucker (pre-retinal fibrosis) as a high risk of treatment is not shown by this study and in fact was more common in the untreated group than the treated group; however the vision of patients with macular pucker in the treated group was generally less than that of those untreated. Recurrent vitreous hemorrhage from bridging or avulsed vessels represented a significant problem following treatment and led to the only case of total visual loss in this study. The prophylactic treatment of acute horseshoe tears with continuing vitreous traction significantly reduces the incidence of subsequent retinal detachment. Whatever method of treatment is chosen by the surgeon, he must follow the principles laid down many years ago by Jules Gonin and completely close the tear. However, it is important to recognize that a new tear or detachment may occur in some cases and seems related to the continuing evolution of the posterior vitreous detachment or residual vitreo-retinal adherence rather than a cause of the treatment itself.

Adult↗

PubMed1995

Cardiovascular effects of varying G-suit pressure and coverage during +1 Gz positive pressure breathing.

With the continued evolution of anti-G suits, used to counter the cardiovascular dysfunction arising from +1 Gz hypoxia protection positive pressure breathing (PPB), it was hypothesized that full-coverage anti-G-suits would offer equal protection while using lower inflation pressures than the traditional 4:1 ratio. Nine experienced subjects were exposed to 2 min of 70 mm Hg PPB while wearing either the COMBAT EDGE (CE) and Tactical Life Support System (TLSS) garments with the G-suit inflated to 4 x breathing pressure, and the Advanced Tactical Anti-G-Suit (ATAGS) at 4, 3, 2, and 1 x the breathing pressure. All subjects were measured with impedance cardiography (IC), and six were measured simultaneously with both IC and the Cardioscint nuclear probe. IC-estimated stroke volume, relative left ventricular (LV) end-diastolic volume, LV ejection fraction, and peak filling rate were depressed most in the CE and ATAGS 1 conditions (p < 0.001). Heart rate and mean arterial blood pressure changes were highest and lowest, respectively, using the CE and ATAGS 1 garments (p < 0.001). There were no differences in these variables between the TLSS and ATAGS 2-4 conditions. Thus, protection against the PPB-induced fall in LV preload and cardiovascular function may still be adequately afforded by lower G-suit inflation pressures when using full-coverage anti-G suits during PPB intended for high altitude-protection.

Blood Pressure↗

PubMed1995

Biologic therapy for osteosarcoma using liposome-encapsulated muramyl tripeptide.

The successful treatment of metastases will have to include modalities that can overcome the obstacles presented by the heterogeneous nature of malignant neoplasms and the continuous evolution of variant cells. Macrophages activated to become tumoricidal by interaction with L-MTP-PE may be able to accomplish this. Osteosarcoma appears to be an ideal disease in which to employ L-MTP-PE as an additional adjuvant to present chemotherapy regimens. The lung is the most frequent site of metastases, and pulmonary micrometastases are considered to be present in the majority of patients at diagnosis. Approximately 40% of patients with osteosarcoma develop pulmonary metastases despite the administration of adjuvant chemotherapy. The 2-year disease-free interval has not improved over the past 10 years, despite multiple changes in adjuvant regimens. These data argue that there is a subpopulation of patients who harbor tumor cells that are relatively resistant to all chemotherapy. Unfortunately, this group of patients cannot be identified at the time of initial diagnosis. This necessitates the incorporation of new forms of therapy into the adjuvant chemotherapy protocols for all patients in the hope of eradicating the resistant cells harbored in the 40%. Based on the data summarized previously, L-MTP-PE may improve the clinical outcome of patients with osteosarcoma by activating pulmonary macrophages to destroy residual tumor cells that are not eliminated by chemotherapy. Monocytes from osteosarcoma patients can be rendered cytotoxic to tumor cells by in-vitro incubation with L-MTP-PE and following the intravenous administration of this agent. L-MTP-PE can be given safely to both adults and children with minimal side effects. The whole-body distribution of 99mTc-labeled liposomes containing MTP-PE confirms that the agent is taken up by the lungs. Biologic activity in osteosarcoma patients is revealed by the elevations in plasma levels of several cytokines plus stimulation of monocyte-mediated cytotoxicity following L-MTP-PE infusion and by histologic changes in the pulmonary lesions. Ifosfamide therapy given in combination with L-MTP-PE does not suppress this immune response, as judged by both plasma cytokine levels and tumor histology. Finally, L-MTP-PE has been shown to be effective as a single agent against relapsed osteosarcoma. It is unlikely that the addition of other chemotherapeutic agents to the adjuvant chemotherapy protocols will alter the 65% to 70% 2-year disease-free survival rate associated with osteosarcoma. The preceding data indicate that L-MTP-PE is an active agent against this disease and deserves further investigation. Therefore, the inclusion of L-MTP-PE with chemotherapy is a reasonable alternative to consider to improve the response rate of this disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1978

[Technology and real performances of a new circuit for new pacemaker (author's transl)].

Continuing evolution in cardiac stimulation today imposes on PM manufacturers the need to submit their products under new criteria, such as: contained dimensions, functional complexity and longer periods of patient care. PM electronic circuity plays a determinant role in meeting the best solution of these problems. Thick film hybrid technology has been chosen by the Authors because it is deemed to be the best compromise for the present goals, such as: low power consumption, low weight and small size, electrical parameters stability, functional complexity and high circuitry density, Hi-Rel performance for longer working life. A little space has been reserved for schematic diagrams of the manufacturing cycle and the applied technology; particular evidence has been shown concerning selection criteria for circuitry component selection and Hi-Rel tests for the end product. Hi-Rel and qualification standards have been selected by the Authors from MIL-STD 883 methods and AAMI-FDA pacemakers standards. Practical results of the application of this methodology can be summarised as follows: only 44-50% of the total circuits pass the complete cycle of tests and thus are used for PM manufacture; electronic failure rate in the implanted units is 0.024% failure per month.

Electronics↗

PubMed1995

Occupational risks in the rubber industry.

Important epidemiologic findings have resulted in safer work conditions over the past decades. Maintaining this improvement in worker risk requires continued epidemiological surveillance for unrecognized dangers and intense enforcement of industrial hygiene principles. It also demands an enhanced clinical suspicion and a low threshold for clinical diagnosis of potentially attributable health problems in workers whose workplace chemical environment is in continual evolution. Clinicians should be familiar with the known associations of work and disease, and remain alert to the possibility of chemically mediated disease in workers exposed to this highly complex mixture of chemical agents.

Chemical Industry↗

PubMedDate not supplied

Larger scale multipin peptide synthesis.

The multipin peptide synthesis approach originated as an immunological tool for epitope mapping. However, continuing evolution of the basic technology has allowed synthesis at scales up to 10 mumol per pin. At this loading, the methodology can no longer be considered just a screening tool. The overall synthesis efficiency of this approach was assessed by the synthesis of 2913 different peptides having little or no sequence homology and ranging up to a 46-mer in length. High performance liquid chromatography analysis of the crude peptides indicates overall quality of synthesis was high. The method is suitable for multi-milligram synthesis of peptides without sacrificing any of the inherent advantages of the 96-well format.

Amino Acid Sequence↗

PubMed1994

Laxity and function in knee replacements. A comparative study of three prosthetic designs.

This study was designed to determine the influence of laxity on clinical function after knee replacement. Using a recently developed computerized method, anteroposterior laxities were measured in 29 Insall-Burstein posterior stabilized, 25 Kinemax Condylar (posterior cruciate retaining), and 10 Oxford bicompartmental (anterior and posterior cruciate retaining) knee replacements. Laxities of less than 5 min, irrespective of implant design, was associated with an impaired range of passive motion and an increased likelihood of incurring a flexion deformity in excess of 4 degrees. Clinical function, as reflected by the American Knee Society Clinical Rating system, demonstrated a particular sensitivity in the Oxford knee to anteroposterior laxity. It was concluded that anteroposterior laxity in excess of 5 mm in prosthetic knees is desirable for unimpaired joint function, although an upper limit of acceptable anteroposterior laxity could not be identified. These findings, which emphasize the need for attention to ligamentous tensions at the time of surgery, also indicate the need for appropriate weighting of anteroposterior laxity in the continuing evolution of clinical rating systems.

Adult↗

PubMed1993

Ruptured abdominal aortic aneurysm: a community experience.

A retrospective review of a community experience with ruptured abdominal aortic aneurysm (AAA) identified 117 cases from five community hospitals over a 12-year period. There were 90 men (77%) and 27 women (23%), ranging in age from 49 to 87 years. In the initial 6 years, the majority of operations were performed by general surgeons, with a survival rate of 35%. In the latter 6 years, most operations were performed by vascular surgeons, with a survival rate of 61%. For the entire period, patient survival with vascular surgeons was significantly greater than that with general surgeons (P < 0.05). Preoperative risk factors assessed in terms of their impact on survival were similar to those of previously reported series. Patients in the latter half of the study were older (72.8 versus 69.9 years), with survivors requiring a longer length of hospital stay than those in the initial 6-year period (34.5 versus 22.5 days), indicative of the changing patient population and having diagnostic-related group implications. There was also increased reliance by emergency room physicians on computed tomography for diagnosis, with increased survival rates. Misdiagnosis (patient sent home or admitted with incorrect diagnosis) occurred in 12 patients with no deleterious impact on survival. Some 15 patients with known AAA who either refused surgery for medical reasons or were considered to be at excessive risk for elective resection had a survival rate of 33%, indicating a definite potential for survival. It is concluded that there is continuing evolution of care for patients with ruptured AAA in the community setting.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMedDate not supplied

Embryology of the urinary tract and prenatal diagnosis of congenital obstructive anomalies.

Fetal malformations within the urinary tract are frequently detected during sonographic examination in the second and third trimester of pregnancy. Detection has been facilitated by a continued evolution of new technological equipment and by increased knowledge regarding the existence of direct sonographic patterns (kidneys) and/or indirect sonographic patterns (amniotic fluid volume). A wide range of variability and severity of such malformations has been noted, from the so-called "functional" types which disappear spontaneously after birth, to those requiring postnatal surgery, as well as those with fatal prognosis. Due to the complexity of the embryological development of the fetal urinary system, the pathogenesis of such malformations is still not well known. The main stages of development of the urinary tract in the embryo were studied in 156 cases involving urinary tract obstructions. Follow-up was strictly adhered to until the postnatal outcome. Sonographic patterns representative of this pathology were studied in order to verify if a correct diagnosis and an accurate definition of the prognosis could be arrived at using the data.

Female↗

PubMed1993

Trimethoprim and brodimoprim resistance of gram-positive and gram-negative bacteria.

Trimethoprim and brodimoprim act by selectively inhibiting bacterial dihydrofolate reductase. There are a number of mechanisms by which bacteria can develop resistance to these agents. These include thymineless mutation, impermeability, alteration in chromosomal dihydrofolate reductase and the plasmid-encoded production of an additional dihydrofolate reductase which is insensitive to inhibition by antifolate agents. Clinically the most important of these is the plasmid-encoded production of additional dihydrofolate reductases and such resistance is found in both gram-positive and gram-negative species. These plasmid-encoded enzymes were initially divided into a number of classes based principally on their biochemical profiles. More recently sequence analysis has been used to study these proteins and thus the classification of dihydrofolate reductases now also takes into account sequence information. The number of plasmid-mediated dihydrofolate reductases has increased markedly in recent years. Whilst this probably results from the continuing evolution of resistance it can also be partly attributed to more discriminatory methods for studying these enzymes.

Folic Acid Antagonists↗

PubMedDate not supplied

A case study in the use of race and ethnicity in public health surveillance.

Increased attention has been focused on the use of racial and ethnic categories in public health research and surveillance in recent years. This attention, however, has done more to increase the collective awareness of the difficulties inherent in these classification schemes than to resolve either the theoretical or practical problems. It has been recognized for many years that health outcomes for a particular ethnic population must be seen as an interaction between genetically determined factors and socially mediated exposures. The operational meaning of these concepts remains poorly defined, however. Although the general biologic construct of race and ethnicity appears straightforward, appearance is deceiving and the technical requirements that allow formulation of a rigorous and objective working definition have never been fully developed. The social factors that influence ethnic health differentials are perhaps better understood in practical terms; measurement of many of the relevant variables remains difficult, however. In this article an attempt is made to outline the implications of the new developments in molecular biology for the concept of race, and to provide an illustrative example of the continued evolution of the social determinants of ethnicity.

Data Collection↗

PubMed1993

Posterior composites. State-of-the-art clinical applications.

Composite resins have undergone a continuous evolution since the first patent developed by Bowen in the middle 1960s. Some current formulations are an order of magnitude more wear resistant than those first used in posterior teeth. In fact, some of them are nearly as wear resistant as amalgam with respect to generalized wear. Unfortunately, however, disproportionally little effort has been expended in improving the resins' manipulative characteristics. Consequently, posterior composite resins presently fall short as an overall substitute for amalgam as a restoration material.

Bicuspid↗

PubMed1993

Ongoing progress in the treatment of childhood rhabdomyosarcoma.

During the past 2 decades, several different multidisciplinary treatment studies of childhood rhabdomyosarcoma have been conducted, some as single-institution protocols and others as multi-institution cooperative endeavors. Much of our current understanding of the natural history and histopathology, as well as response to treatment, is derived from these studies. This understanding has allowed for the continued evolution of treatment, which has already resulted in a dramatic increase in overall survival rates. Current treatment trials are aimed at maintaining high cure rates while reducing treatment-related morbidity, and exploring innovative regimens to improve the outlook of poor-risk patients. The improved outcome in children with rhabdomyosarcoma is a tribute to the multi-institutional, multidisciplinary approach to cancer research and treatment.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1993

Questions of life and death.

The continuous evolution of health care technology has brought with it a growing need to evaluate the quality of the lives it saves or prolongs. Do Not Resuscitate (DNR) orders, euthanasia and living wills all raise the issue of who decides about the quality of a person's life. Although nurses and other health care professionals have developed codes of ethics to deal with these difficult evaluations, ethics are not law. Ethics are derived from culture, religion and societal and individual concepts of morality. Law is the set of rules a society chooses to enact and enforce. Real difficulty arises when health care providers must face a situation where personal and professional codes of ethics clash with the law.

Decision Making↗

PubMed1993

The impact of technology on patients and families.

The continuing evolution of the highly specialized, technologic manner in which we provide care in critical care units has potentially hazardous effects on the physical and psychological well-being of patients and family members. Although the ICU environment possesses characteristics that make patients and families prone to undesirable sequelae, critical care nurses can employ creative strategies to minimize the impact of bedside technology that is so important for the survival and recovery of the critically ill patient. Strategies to reduce the psychological impact of the ICU environment begin with a psychosocial assessment of the meaning patients and families attach to bedside technology. This assessment will strengthen nurse, patient, and family interactions, as well as guide patient and family education and sensory information to reduce fear and anxiety often associated with threatening procedures. Facilitating touch and family involvement in the patient's care during visitation is another strategy to humanize the technologic environment. Managing the environment is essential to reduce the physical impact of the ICU environment. Nurses can manipulate the use of equipment to reduce crowding and noise at the bedside, foster familiar activities to stimulate the patient's other senses, and facilitate sleep patterns by structuring nursing activities and providing comfort measures. These nursing interventions will reduce the effects of sensory overload/deprivation and sleep deprivation and, it is hoped, prevent ICU psychosis.

Anxiety↗

PubMed1995

The evolution of a scalable departmental real-time clinical information system.

On-line Clinical Information Systems have to be both very responsive and capable of accessing large volumes of historic data. The EmStat Emergency Department Clinical Information System has evolved through several approaches to meeting these needs, including effective use of client/server technology, and optimizing all available machine resources. Currently the system is quite successful in this regard but the evolution continues.

Computer Systems↗

PubMed1996

Caval interruption methods: comparison of options.

The Stainless Steel and Titanium Greenfield filters, the Venatech filter, and the Bird's nest filter are most commonly used in the United States. A comparison of contemporary experience with these filters along with that of Simon-Nitinol filter is shown in Table 1. The published experience with each device is minimal compared with actual clinical use. The published reports available do not often examine experience with a view toward unbiased and accurate comparison of results. Each filter has an acceptably low rate of recurrent PE, but each has experienced the range of complications associated with vena caval filters or partitions. The reviewed case series are too small and the complication rates too similar for any of the newer designs to claim unequivocal superiority. Except for the Stainless Steel Greenfield filter, comparison is further complicated by the lack of standardized, quantitative follow-up of patients over a period long enough for possible extremity venous complications to be observed. Each of the currently available filters has at least one specific attribute that may recommend it for a particular situation. Detailed and comparable examination of IVC filtration is becoming more important as the indication for and use of these devices increase. Clearly, the search for the perfect device to prevent PE should continue.90 Any filtration device plays only a small role in the overall management of the patient with thromboembolic disease. It is incumbent upon the physician who treats this patient to assume the responsibility for the diagnosis of and long-term follow-up of the underlying disorder. Considerable technical ingenuity and continued evolution of materials and design have propelled the development and number of available vena cava filters for clinical use. Without objective clinical data, many interventional radiologists and surgeons base their filter selection on ease of insertion and device cost. Variable data on safety and effectiveness demand that physicians match the best filter to each patient's particular situation and anatomy. The primary objective of vena cava filtration is to provide a safe and effective device for permanent implantation. If this objective is not kept in sight, quality of care in the management of deep venous thrombosis and/or pulmonary embolus will be lost.

Clinical Trials as Topic↗