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At least 379 records · Page 21Linked to original sources
PubMed2006

A short enantioselective pathway for the synthesis of the anti-influenza neuramidase inhibitor oseltamivir from 1,3-butadiene and acrylic acid.

A short synthetic pathway has been developed for the synthesis of oseltamivir (1) or the enantiomer (ent-1). The intermediates and conditions for this process are summarized in Scheme 1. The synthesis provides a number of advantages: (1) use of inexpensive and abundant starting materials; (2) complete enantio-, regio-, and diastereocontrol; (3) avoidance of explosive, azide-type intermediates; (4) good overall yield (ca. 30%, still not completely optimized); and (5) scalability.

Acrylates↗
PubMed2004

The plot thickens: New perspectives of primary cell wall modification.

Recent studies have further confirmed the ubiquity of cell wall restructuring during plant growth and development, and have emphasized the fact that our understanding of the breadth of molecular processes that mediate wall modification is still rudimentary. In the past few years, both enzymatic and non-enzymatic agents that apparently contribute to wall disassembly have been identified, and it is likely that additional mechanisms will continue to be revealed. These discoveries are being propelled by the development of new biochemical and biophysical assays, by database mining in the wake of the explosion of plant sequence information from genome sequencing and expressed sequence tags, and by a variety of strategies used to catalog the cell wall proteome. The daunting question of how these mechanistically diverse and complex processes are coordinated remains unresolved.

Arabidopsis↗
PubMedDate not supplied

Orgasmic headache with transient basilar artery vasospasm.

A 36-year-old man without significant past medical history presented with recurrent explosive headache at the time of orgasm. Magnetic resonance angiography showed focal mid-basilar artery narrowing. Despite receiving no specific therapy, the patient's headaches and vascular narrowing had resolved completely on follow-up six months later. While a number of pharmacologic agents have been proposed to be of benefit in orgasmic headache, this case suggests that spontaneous resolution may also occur.

Adult↗
PubMed1984

The role of prostaglandins in obstetrics/gynecology.

After a lag between the recognition of the biologic activity of material derived from seminal vesicles and the actual isolation and identification of prostaglandins, information on the structure, biosynthesis, physiology, and biomedical relevance of this family of substances has expanded explosively in recent years. Their ubiquitous presence in mammalian tissues has contributed to the intense interest in and investigation of their role in normal physiology and a variety of pathologic states. The availability of pure compounds of known chemistry, as well as of numerous agents that interfere with their production or metabolism, continues to allow unravelling of their regulatory influences, mechanism of action, and participation in disease processes. Understanding of the role of prostaglandins in reproductive physiology has led to widespread and effective applications in clinical obstetrics and gynecology, including menstrual disorders, therapeutic abortion, and labor. Their implication in the pathogenesis of toxemia of pregnancy, coupled with expanding information on the general role of prostaglandins in the regulation of hemostasis, has advanced understanding of hemorrhagic and thromboembolic disorders and opened innovative avenues for potential therapeutic intervention.

Abortion, Induced↗
PubMed1998

Problems with antimicrobial resistance in gram-positive cocci.

The development of antimicrobial resistance has almost invariably accompanied the therapeutic use of antimicrobial agents. Newer antimicrobials have succeeded partly but not entirely in overcoming the problem of resistance. Antimicrobial resistance in gram-positive cocci has achieved its greatest prominence in the past 15 years. There has been a steady erosion of antimicrobial activity against gram-positive cocci. The presentations in this symposium dealt with some of the important problems of antimicrobial resistance in gram-positive cocci, including methicillin resistance and multidrug resistance in staphylococci, penicillin resistance in pneumococci, and vancomycin resistance in enterococci. A related problem that warrants attention is the potential for explosive development of macrolide resistance in gram-positive cocci. This potential is particularly pertinent because the popularity of a number of new macrolides has led to a striking increase in their use. This occurrence will almost certainly be accompanied by a generalized increase in resistance in gram-positive cocci.

Anti-Bacterial Agents↗
PubMed2003

Advances in management of sickle cell disease.

Sickle cell disease is numerically as common as thalassaemia. However, it affects relatively under privileged population i.e. tribal population belonging to economically poor class and having inadequate access to education and modern health facilities. A recent explosion acknowledged in understanding the pathogenesis of this disease has lead to newer dimensions in treatment. Some of these viz. prevention of overwhelming bacterial infection, present indications and controversies regarding blood transfusion, prevention of stroke, acute chest syndrome, hydroxyurea therapy--probably the best disease modifying agent at the moment, stem cell transplantation--a cure and certain promising experimental therapies including gene therapy have been discussed in this review.

Acute Disease↗
PubMed2002

Identification of nitrate ester explosives by liquid chromatography-electrospray ionization and atmospheric pressure chemical ionization mass spectrometry.

Liquid chromatography-mass spectrometry (LC-MS) with electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI), in the negative-ion mode, was investigated for the analyses of three widely used nitrate ester explosives, pentaerythritol tetranitrate, nitroglycerin and ethylene glycol dinitrate, as well as six additional nitrate esters, using post-column additives. In ESI, ammonium nitrate, sodium nitrite, propionic acid and ammonium chloride promoted formation of characteristic adduct ions of the respective nitrate esters. In APCI, chlorinated agents, dichloromethane, chloroform, carbon tetrachloride and ammonium chloride, were employed, fanning chloride attachment adduct ions. Three forensic samples, Booster DYNO, Semtex and Smokeless Powder, were analyzed to demonstrate the validity of the developed LC-MS methods.

Atmospheric Pressure↗
PubMed2000

Psychologic and psychiatric aspects of gastrointestinal disease.

There has been an explosion in understanding of the psychosocial concomitants of functional gastrointestinal disorders. Detecting psychologic disturbance and eliciting a history of physical or sexual abuse are critical in suggesting comprehensive and efficacious treatment strategies for these patients. The challenge is to define further the use of psychopharmacologic agents, including the newer antidepressants, anticonvulsants, and anxiolytic agents, in the treatment of chronic functional gastrointestinal disorders. Further research to evaluate the usefulness of various forms of psychotherapeutic and behavioral interventions needs to be undertaken. Establishing a multicomponent treatment program delivered by a team of caregivers, each bringing their unique skills (internist, psychiatrist, psychologist, and others) to patients, must be based on further research on the efficacy of these modalities as opposed to empiric treatment.

Anti-Anxiety Agents↗
PubMed2004

[Physiopathology of severe sepsis].

Regarding the definition. Severe sepsis associates an explosive inflammatory reaction and organ failure. It is secondary to bacterial, fungal or viral infection. It can be at the origin of acute circulatory failure (state of septic shock). Response of the organism to infection. The presence of certain components of the membrane of pathogenic agents induces the release of various mediators in cascade, notably cytokines. Toll-like receptors (10 cloned in humans) intervene in the detection of microbes and in the inherent and subsequently adaptive immune response. Immune paralysis. The release of pro-inflammatory mediators characterizes the initial phase of sepsis. Persistence of the latter provokes acquired immunodepression, related to an anti-inflammatory profile, and hence to a delayed decrease in hypersensitivity, an incapacity to cope with the infection and the onset of nosocomial infections. The role of the mediators. During sepsis, the cytokines are predominantly pro-inflammatory (TNF-alpha and notably IL-1beta) whereas others, produced concomitantly or subsequently, are predominantly anti-inflammatory (IL-10 in particular). In fact, the majority of the cytokines have multiple and intrinsic effects, they mediate immune defense but also pathological manifestations. Many other mediators intervene: coagulation or complement systems, contact system, breakdown products of the phospholipid membrane, arachidonic acid metabolites, free radicals and nitrous oxide. Endocrine and metabolic dysregulations. The concept of relative adrenal insufficiency and peripheral syndrome of resistance to glycocorticosteroids have led to hormone replacement therapy during septic shock. Acute insulin resistance has also been described. The role of the endothelium and coagulation. The endothelium plays a key part in the onset of vascular insufficiency during sepsis due to abnormalities in vasomotricity and thrombomodulation. The anticoagulant regulating system is perturbed; there is a decrease in protein C with inactivation of its active form, which has pro-fibrinolytic properties, and a decrease in antithrombin III. Regarding myocardial dysfunction During septic shock there is often severe left ventricular systolic dysfunction, sometimes also involving the right ventricle, largely under-diagnosed despite its severe prognosis, and associated with reduced or even collapsed heart rate.

Animals↗
PubMedDate not supplied

Early and explosive development of nodular basal cell carcinoma and multiple keratoacanthomas in psoriasis patients treated with cyclosporine.

The use of cyclosporine to treat psoriasis has been widely adopted since 1997, when the microemulsion form (Neoral) became available. While the causal relationship between cyclosporine and the development of malignant neoplasms has been well described in the transplant literature, it is difficult to apply this relationship to cyclosporine-treated psoriasis, since lower dosages are used (3-5 mg/kg/d vs. 7-15mg/kg/d) for a shorter duration. Current literature suggests that cancer risk is not increased when cyclosporine is used in dermatologic doses for less than 2 years in healthy patients who are not on other immunosuppressants. We report two patients with explosive basal cell carcinoma and keratoacanthoma development, respectively, within 3 months of initiation of cyclosporine. Neither patient had a history of skin cancer, had received PUVA therapy, or was on additional immunosuppressive therapy. To our knowledge, there have been no previous reports of the development of similar lesions in cyclosporine-treated psoriatic patients within such a short timeframe. The results of these patients may herald the need for increased awareness by dermatologists for explosively-growing neoplasms in the setting of cyclosporine-treated psoriasis.

Basal Cell Carcinoma↗
PubMed2001

Effects of blasting fumes on exposure and short-term lung function changes in tunnel construction workers.

OBJECTIVES: This study attempts to determine the effects of exposure to blasting fumes and its influence on the lung function of tunnel workers. METHODS: Two groups of tunnel workers, one using ammonium nitrate fuel oil (ANFO) as the explosive and the other using size-sensitized emulsion (SSE), with 24 workers per group, were compared with a reference group (N=34) with low exposure. Spirometry was used to determine lung function. Personal exposure to total and respirable dust, alpha-quartz, volatile organic compounds, oil mist and vapors, formaldehyde, nitrogen dioxide, and carbon monoxide was measured. RESULTS: The ANFO workers were more exposed to all the agents than the reference group and more exposed than the SSE workers to all the agents except total dust and carbon monoxide. The SSE workers were significantly more exposed to total dust and alpha-quartz than the reference group. High peak exposures to nitrogen dioxide (up to 20 ppm) occurred for the ANFO workers in contrast to the SSE workers, whose exposure did not exceed 2 ppm. The lung function of the ANFO workers significantly decreased by 3% for forced vital capacity, 7% for forced expiratory volume in 1 second, and 8% for forced expiratory flow rate from 25% to 75% of the forced vital capacity over the 11-day period. The changes were reversible. There were no significant changes among the SSE workers and the outdoor workers. The ANFO workers had a significant decrease in FEV1.0 when compared with both the SSE and outdoor workers. CONCLUSIONS: Tunnel workers using ANFO explosive show a temporary reduction in lung function, whereas those using SSE do not. The most likely explanation for the observed changes is peak exposures to nitrogen dioxide.

Adult↗
PubMed2000

Novel non-operative treatment and treatment strategies in pancreatic cancer.

Patients with advanced pancreatic cancer have traditionally been treated with palliative care only. The last decade has seen significant improvements in the surgical treatment of this disease but until the late 1990s there was no effective non-surgical treatment for these tumours. The introduction of gemcitabine has given clinicians treating patients with pancreatic cancer a new option. The published randomised data of gemcitabine in patients with pancreatic cancer has shown both a small survival advantage and significant improvements in quality of life indicators in these patients. These data have stimulated a resurgence of interest in pancreatic tumours and several studies have been or are currently investigating novel treatments or treatment strategies. The explosion in the molecular knowledge of cancer has led to the development of several 'molecular designer drugs' that have been tested in pancreatic cancer. The furthest advanced of these is a matrix metalloproteinase (MMP) inhibitor called marimastat. The first randomised data using this new class of agents is increasing and suggests that marimastat may have a role in the future treatment of patients with pancreatic cancer. Other agents such as gastrimmune, are about to enter Phase III studies and several other molecular treatment strategies are progressing from the in vitro stage towards the clinical arena. Each of these treatments and treatment regimens are discussed along with their current progress.

Animals↗
PubMed1997

[Methods for reduction of homologous blood transfusions in operative medicine].

For ethical and socio-economical reasons (cost-explosion in transfusion-medicine, patient's individual destiny), development and consistent application of allogeneic transfusion sparing techniques in surgery is a challenge to anesthesiologists, surgeons and blood-bankers. The combination of different techniques, i.e. autologous predonation, hemodilution, choice of anesthetic regimen, deliberate hypotension, application of antifibrinolytic agents and autotransfusion of intraoperatively saved blood allow for avoidance of allogeneic blood transfusion even in patients presenting important intraoperative hemorrhage. The present article summarizes (1) risks associated with transfusion of allogeneic blood, (2) actually applied pre- and intraoperative techniques to reduce transfusion of allogeneic blood and (3) new concepts (administration of erythropoietin, hyperoxic ventilation and administration of artificial oxygen carries) to further increase the efficacy of autologous predonation and preoperative normovolemic hemodilution.

Humans↗
PubMed1983

Ocular complications of Wegener's granulomatosis.

140 patients with biopsy-proven Wegener's granulomatosis were examined during a 16-year period at the Mayo Clinic. Forty patients had diverse and explosive ophthalmic involvement, including conjunctivitis, episcleritis, scleritis, corneal ulceration, uveitis, retinal vasculitis, optic neuropathy, orbital mass, orbital cellulitis, and obstruction of the nasolacrimal duct. The multiple ophthalmic and systemic complications in these 40 patients and the importance of establishing the pathologic diagnosis are discussed. Treatment with corticosteroids and immunosuppressive agents has dramatically improved the prognosis, although substantial mortality (four patients died of Wegener's granulomatosis) and ocular morbidity (three eyes were enucleated) are still associated with this disease.

Adolescent↗
PubMed2003

[Pathogenesis of type 2 diabetes mellitus].

"Common" type 2 diabetes mellitus is a multifactorial disease. Hyperglycemia is related to a decrease in glucose peripheral uptake, and to an increase in hepatic glucose production, due to reduced insulin secretion and insulin sensitivity. Multiple insulin secretory defects are present, including loss of basal pulsatility, lack of early phase of insulin secretion after intravenous glucose administration, decreased basal and stimulated plasma insulin concentrations, excess in prohormone secretion, and progressive decrease in insulin secretory capacity with time. These genetically determined abnormalities appear early in the course of the disease. Insulin resistance affects muscle, liver, and adipose tissue. For the same plasma insulin levels, peripheral glucose uptake and hepatic glucose production suppressibility are lower in diabetic patients than in controls. It results from aging of the population and from "western" lifestyle, with progressive increase in mean body weight, due to excess in energy intake, decreased energy expenses and low physical activity level. NEW ASPECTS: The role of beta-cell dysfunction, as well as the interplay between insulin secretory defect and insulin resistance are now better understood. In subjects with normal beta-cell function, increase in insulin needs secondary to insulin resistance is compensated by an increase in insulin secretion adjusted to maintain plasma glucose levels to normal. In subjects genetically predisposed to type 2 diabetes, failure of beta-cell to compensate for increased needs is responsible for a progressive elevation in plasma glucose levels, then for overt type 2 diabetes. This adaptative phenomenon is called beta-cell compensation of insulin resistance. The lack of compensation is responsible for type 2 diabetes. When permanent hyperglycemia is present, progressive insulin secretory failure with time ensues, due to glucotoxicity and to lipotoxicity. PERSPECTIVES: Simple changes in lifestyle, such regular moderate physical activity, and control of body weight, should permit to avoid the explosion in prevalence of type 2 diabetes. This has been evidenced by the results of prospective studies aiming at preventing conversion from impaired glucose tolerance to diabetes. In patients with permanent hyperglycemia not controlled by lifestyle changes, metabolic defects are the targets of specific therapy intervention with antidiabetic oral agents, such as insulin secretagogues, insulin sensitizers, and inhibitors of hepatic glucose production.

Diabetes Mellitus, Type 2↗
PubMed1992

Immunomodulators: current and future development and application.

It has been amply demonstrated that immunomodulators have a place in the armamentarium with other therapeutic modalities for the treatment of various diseases. They presently are, and in the future will be, most effective in preventing diseases which cause, or are the result of, immunodeficiencies. For future development the biological agents that are potent immunomodulators can be more purified and their molecular structures defined and synthesized, such as muramyldipeptides are products of BCG, etc. The active moiety of Picibanil (OK 432), a very powerful immunostimulator should be defined. Further investigations in isolating and characterizing biological agents as immunomodulators should continue in view of the success that has been achieved with BCG in treating superficial transitional cell bladder carcinoma. This mode of treatment is much less toxic to the patient than treatment with the cytotoxic agents thiotepa, mitomycin C. Chemically defined immunomodulators have been used successfully when combined with other therapeutic modalities. Levamisole and its additive therapeutic effect when combined with 5-FU in the treatment of Stage C colorectal carcinoma establishes the potential usefulness of chemicals which specifically augment the immuno response. The explosive growth of cytokine research has led to many technical advances which were key to give cloning and the availability of recombinant cytokines which have extended and modified our concepts of cytokines. The capability of cloning to provide considerable quantities of pure cytokines, permitted studies of immunological, physiological, and therapeutic roles of cytokines. All three classes of immunomodulators: biologicals; chemical; and cytokines will continue to play a major role in advancing and improving the quality of treatment of several of human as well as animal diseases.

Adjuvants, Immunologic↗
PubMed1993

[Multiresistant tuberculosis in New York].

New Yorkers have to deal with a tuberculosis situation which is of greater extent and a health-care system which is less prepared than in the sixties. Poverty and the HIV epidemic have had a negative impact on the control of tuberculosis. The emergence of nosocomial multidrug-resistant tuberculosis has created an explosive situation. In 1991, rifampin resistance was 33% in patients who had received antituberculosis therapy and 10% among the patients who had never been treated.

AIDS-Related Opportunistic Infections↗