Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Therapy development”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 487 records · Page 27Linked to original sources
PubMed1985

Pneumonia treated with imipenem/cilastatin.

In an open, prospective, multicenter trial the efficacy and tolerance of imipenem/cilastatin for the treatment of bacterial pneumonia was investigated. Forty-three adults were studied: 29 with nosocomial and 14 with community-acquired infections. Significant underlying disease was present in 91 percent of patients. Nosocomial infection was frequently associated with endotracheal intubation (48 percent), prior antibiotic therapy (48 percent), and recent surgery (31 percent). Most frequent sputum isolates included Pseudomonas aeruginosa (10, all nosocomial), Hemophilus influenzae (10), Escherichia coli (eight), Staphylococcus aureus (seven), and Streptococcus pneumoniae (six). Treatment with imipenem/cilastatin was associated with clinical cure in 93 percent of patients. Two of three failures and one superinfection occurred in association with isolates of Pseudomonas aeruginosa resistant to imipenem. Overall, six of 10 strains of Pseudomonas aeruginosa isolated prior to therapy developed resistance to imipenem after an average of 10 days of therapy. Adverse effects occurred in nine patients (21 percent) and included one case of pseudomembranous colitis. Monotherapy with imipenem/cilastatin of serious lower respiratory tract infections was relatively safe and highly effective with the exception of disease associated with P. aeruginosa.

Adult↗
PubMed2001

Review article: the limitations of corticosteroid therapy in Crohn's disease.

Corticosteroids are highly effective in inducing clinical remission in patients with active Crohn's disease. However, the role of corticosteroids in the treatment of this disease is primarily ameliorative because they are ineffective in maintaining remission or healing mucosal lesions. Nearly half of the patients who initially respond to corticosteroid therapy develop a dependency on corticosteroids or have a relapse within 1 year. In addition, use of these agents is often limited by a relatively high risk of serious adverse effects that can involve nearly every major body system. These effects include: bone loss, which can develop with even short-term and low-dose corticosteroid therapy; metabolic complications such as glucose intolerance and diabetes mellitus; increased intraocular pressure and glaucoma; and potentially lethal infections. To minimize the risk of toxicity, corticosteroids are increasingly recommended for short-term use only at the lowest effective dose to induce remission in patients with moderately to severely active Crohn's disease. Corticosteroid formulations with low systemic bioavailability, such as controlled-release budesonide, may be associated with a lower rate of dermatologic adverse effects but appear to be somewhat less effective than conventional corticosteroids in inducing remission in patients with active Crohn's disease. Immunosuppressive agents such as azathioprine, 6-mercaptopurine, and methotrexate have demonstrated corticosteroid-sparing effects, facilitating the withdrawal of corticosteroids when initiated as maintenance therapy. Infliximab can be used as an alternative to corticosteroids.

Anti-Inflammatory Agents↗
PubMed1988

Atypical mycobacterial infection in alpha interferon-treated hairy cell leukaemia.

A patient whose hairy cell leukaemia had begun to respond to alpha interferon therapy developed overt atypical mycobacterial infection. This eventually responded to combination antimicrobial therapy. The clinical difficulties involved in this unique case included difficulty in isolation of the organism, failure of an empirical trial of antituberculous therapy and false attribution of the patient's infective symptoms to alpha interferon.

Aged↗
PubMed2001

Thyroid storm in a child following radioactive iodine (RAI) therapy: a consequence of RAI versus withdrawal of antithyroid medication.

A 7.5-yr-old boy with Graves' disease, difficult to control with antithyroid medication and radioactive iodine (RAI) therapy, developed thyroid storm encephalopathy on day 13 after withdrawal of methimazole therapy, 4 days after iodine-131 treatment. We attributed his thyroid storm to withdrawal of antithyroid medication as opposed to RAI therapy. We interpret this case as indicating that there may be a need to reevaluate the duration of antithyroid medication withdrawal before RAI therapy for hyperthyroid children at increased risk for thyroid storm.

Antithyroid Agents↗
PubMed2003

Decision tree and paradigms of primary breast cancer: changes elicited by preoperative therapy.

A small difference in decision-making causes a big impact on the long-term outcome in cancer treatment. Novel methods such as preoperative systemic treatment or sentinel node biopsy (SNB) may alter the decision-trees in primary breast cancer management. Recent data showed that preoperative chemotherapy drives pathological complete response (pCR) that implies long-term relapse-free, for about 25% to 30% of early breast cancer patients. In fact, preoperative systemic therapy has come to be used regardless of the tumor stage. From the point of the clinical trial, pCR can be recognized as a new endpoint, which promises to speed up new therapy development. Therefore, it is crucial to consider new paradigms including preoperative therapy in the decision-tree. There are several criticisms regarding the preoperative therapy, such as a possibility of over-treatment, however these issues might be resolved by changing the concept or procedures slightly. For instance, if SNB is conducted before the treatment, the over-treatment issue can be eliminated. In this article, we will discuss the changes in decision-tree and paradigms for primary

Antineoplastic Agents↗
PubMed1978

[Exfoliative cytology during topical treatment of oral leukoplakia with vitamin A acid].

Vitamin A acid (VAS) has proved itself an effective local therapeutic agent for intra-oral leucoplakia. Clinical remission characterized by a decrease in horny lumps and the eosinophilic index and an increase in intermediary cells was achieved in 32 out of 50 cases. In the course of maintenance therapy development towards an exfoliocytologically healthy mucosa proceeds via increasing parakeratosis. VAS therapy is essentially thought of as symptomatic therapy.

Administration, Topical↗
PubMed2002

Idiopathic inflammatory myopathy: management and prognosis.

We are entering an exciting era in our understanding and management of the connective tissue diseases and, in particular, inflammatory myopathy. There is an established array of immunosuppressive regimens available to clinicians; rehabilitative and physical therapeutic interventions are evolving to provide many nonpharmacologic options to complement current therapy. Our ability to quantify [table: see text] the disease burden, using newly developed tools to distinguish myositis disease activity from disease damage, will allow us to measure with greater sensitivity the effects of treatment interventions. These measures, together with the development of international consensus regarding the standardization of many clinical trial design parameters, will enhance our capacity to conduct well-designed, prospective, multicenter studies of established and newly developed therapies. The explosion of immunopathogenetic information, in conjunction with novel biologic agents (Table 4), will afford investigators a treatment menu with multiple therapeutic options. The continuing challenge for the practitioner is the development of a logical, well-studied, multifaceted, and multidisciplinary holistic approach that optimizes the risk: benefit ratio for each individual patient and uses a rational combination of immunomodulatory agents in conjunction with ancillary measures.

Biological Products↗
PubMed1982

Diagnostic imaging of focal nodular hyperplasia of the liver developing during nitrofurantoin therapy.

An asymptomatic palpable liver tumor developed in a six-year-old girl seven months after commencement of prophylactic nitrofurantoin therapy for recurrent urinary tract infections. The tumor was examined by 99mTc colloid radionuclide scan, compound ultrasonography and angiography. Ultrasonography demonstrated a large, solid tumor (5 x 5 x 8 cm) in the right lobe of the liver which had an echogenic central core surrounded by an area giving low-amplitude echoes. Angiography disclosed that the tumor was well demarcated and hypervascular, containing large tortuous arteries. The uptake of radionuclide in the tumor was normal. The tumor was resected and the pathological findings were typical for focal nodular hyperplasia (FNH) of the liver. The combination of the findings of these three diagnostic imaging methods is probably specific for uncomplicated FNH, a benign and innocuous tumor of the liver.

Aorta, Abdominal↗
PubMed1999

Anaphylactic response to factor IX replacement therapy in haemophilia B patients: complete gene deletions confer the highest risk.

Haemophilia B is an X-linked recessive coagulopathy due to mutations in the factor IX gene. Occasionally, patients receiving factor IX replacement therapy develop inhibiting antibodies to the factor IX protein, and it has been recently documented that a subset of these patients have had anaphylactic responses to factor IX replacement therapy in association with the development of inhibiting antibodies. To determine the relationship between mutation type and the risk of anaphylaxis, eight unrelated patients from families in whom anaphylaxis had occurred were genotyped. The mutations were compared to those in 550 haemophilia B patients and to those in 276 patients with clinically severe disease. Individuals with complete gene deletions were found to be at greatest risk for anaphylaxis, with an estimated risk of 26% or greater. Anaphylaxis was less likely to occur in patients with protein truncation mutations or partial gene deletions and least likely to occur with missense mutations. Genotypes can help physicians and patients anticipate the likelihood of anaphylaxis, a potentially life-threatening complication of factor IX replacement therapy. The very high risk of anaphylaxis associated with a complete gene deletion suggests that the lack of expression of a partial protein product may predispose to anaphylaxis and/or that the absence of a closely linked, codeleted gene enhances the anaphylactic immune response.

Anaphylaxis↗
PubMed2004

The development of gene therapy for diseases of the lung.

The development of a successful gene therapy has many stages, including preclinical testing in animal models and proof of principle clinical studies. A variety of diseases affect the lung, which are candidates for gene therapy; this review will mainly focus on the diseases that have attracted the most attention and have therefore yielded the most progress, namely lung cancer and the monogenic disorder cystic fibrosis. Knowledge gained from clinical studies could eventually be applied to more complex lung conditions such as acute respiratory distress syndrome and asthma. In addition, increased gene transfer efficiencies could be obtained by appropriate selection of the gene transfer vector and mode of delivery.

Animals↗
PubMed1982

A comparative study of the effect of oestrogen substitution therapy on breast development in girls with hypo- and hypergonadotrophic hypogonadism.

During treatment of girls with oestrogen deficiency we observed different patterns of breast development in response to therapy. The forty-five girls studied fell into four groups: Group A, gonadal dysgenesis; Group B, isolated gonadotrophin deficiency; Group C, multiple pituitary hormone deficiencies; Group D, congenital adrenal hyperplasia (17-alpha-hydroxylase deficiency). Treatment with oestrogen was given in an identical manner to all. In the patients with gonadal dysgenesis, in whom the hypothalamic-pituitary function was normal, treatment led to full breast development. In isolated gonadotrophin deficiency and multiple pituitary hormone deficiency breast development was incomplete even after 3 years or more of oestrogen treatment. The conspicuous difference in the hormonal status is that the latter two groups lack gonadotrophins, while in gonadal dysgenesis these hormones are grossly elevated. Our conclusion is that gonadotrophins play an important role in mammary gland development, a finding not previously described. In the girl with 17-alpha-hydroxylase deficiency we observed that cortisol was necessary, in addition to sex hormones, for normal breast development.

Adolescent↗
PubMed1993

Nitrate therapy and the development of tolerance.

The efficacy of organic nitrates in the treatment of acute episodes of angina pectoris is unquestioned. However, long-term use of these agents is associated with the development of tolerance or of reduced efficacy over time when given in doses or formulations that maintain therapeutic blood levels for 24-hour periods. Thus, the role of long-term use of nitrates in prophylactic treatment of stable angina has been questioned. The purpose of this brief review is to evaluate nitrate tolerance, a key issue in the prophylactic use of nitrates, as well as to review what is known about clinical rebound. These issues are discussed, and ways of preventing tolerance development are explored. Intermittent therapy involving a dose-free interval during each 24-hour period helps prevent tolerance.

Angina Pectoris↗
PubMed1995

Early interferon therapy and abortion of posttransfusion hepatitis C viral infection.

We studied the role of an "early" 4-month course of interferon therapy on posttransfusion viral hepatitis C (PTH-C). Paired serum samples of 51 consecutive recipients, taken before and 7-20 days after blood transfusion, were prospectively tested for hepatitis C virus ribonucleic acid (HCV RNA) using the polymerase chain reaction assay. Seven recipients experienced seroconversion of HCV RNA after transfusion. Two of the seven patients underwent an early 4-month course of interferon alpha therapy at a dose of 3 mU per day for 5 days during the first week, then three times a week for the subsequent 15 weeks. The first patient was treated at a very early stage of acute PTH-C and responded well to interferon therapy. Acute PTH-C in the second patient was prevented by interferon therapy. Both patients had normal serum alanine aminotransferase levels and tested negative for anti-HCV and HCV RNA 12 months after the end of treatment. Four of the five patients not on interferon therapy developed abnormal serum alanine aminotransferase activities more than five times the normal upper limit (383 +/- 143 IU/L) at 2-18 weeks after transfusion. All four patients experienced seroconversion of anti-HCV, and three patients developed chronic hepatitis. This study suggests that early long-term interferon therapy has the potential to prevent PTH-C.

Adult↗
PubMed1999

Direct medical charges associated with myocardial infarction in patients with and without diabetes.

OBJECTIVES: This study was designed to measure the direct medical charges for patients with and without diabetes who experience myocardial infarction. METHODS: We completed a retrospective cohort analysis (from the third-party payer perspective) to determine the total direct medical charges (eg, hospitalizations, outpatient visits, pharmacy, and emergency room visits) incurred by an inner city sample of 293 patients during the 12 months following myocardial infarction during the period from January 1993 through February 1997. RESULTS: The 87 patients with diabetes had a higher per patient total direct medical charge (inclusive of initial hospitalization) compared to the 206 patients without diabetes ($18,577 versus $26,414) and approximately $3000 more per person year of observation. Hospitalizations (initial and during the follow-up period) accounted for 88% of the total direct medical charges. The mean charge for the initial hospitalization was higher for patients with diabetes ($12,730 versus $15,394). In a subset, the mean charge per cardiovascular-related hospitalization that occurred during the follow-up period was also higher for patients with diabetes ($6344 versus $9648). CONCLUSIONS: Consistent with what we expected, patients with diabetes incurred higher total direct medical charges as a result of and following myocardial infarction. These data can be used in future cost-effectiveness evaluations for therapies developed to treat patients with diabetes who experience myocardial infarction or for therapies designed to reduce the risk of macrovascular complications associated with diabetes.

Adult↗
PubMed1989

Amiloride. Antiarrhythmic and electrophysiologic actions in patients with inducible sustained ventricular tachycardia.

This study assessed the antiarrhythmic activity of amiloride in 35 patients with inducible sustained ventricular tachycardia. Patients had failed to respond to 3.6 +/- 1.0 antiarrhythmic drugs. Ventricular tachycardia was reproducibly induced by programmed electrical stimulation in all patients at the baseline study. Amiloride was given at 10 and 20 mg/day p.o. on a twice-daily schedule that achieved serum concentrations of 21 +/- 17 and 36 +/- 18 ng/ml, respectively. The mean left ventricular ejection fraction was unchanged from 36 +/- 14% at baseline to 37 +/- 17% during amiloride treatment. Amiloride significantly increased serum potassium from 4.6 +/- 0.4 to 5.1 +/- 0.4 mM. Four patients failed amiloride therapy with spontaneous nonsustained ventricular tachycardia. The remaining 31 patients were assessed by repeat programmed stimulation. Six patients had complete antiarrhythmic response, and an additional six patients had less than 15 beats of ventricular tachycardia induced. Therefore, amiloride was an efficacious antiarrhythmic treatment in 12 of 35 (34%) patients. Amiloride concentrations were significantly higher (52 +/- 20 ng/ml) in patients that responded than in patients that did not respond (30 +/- 15 ng/ml). The only electrophysiologic measurement that changed significantly was the ventricular functional refractory period (from 269 +/- 24 to 283 +/- 25 msec, p less than 0.05). Amiloride also suppressed frequent, spontaneous ventricular premature beats in eight of 15 patients (53%). No somatic side effects occurred. Two of the five patients discharged on amiloride therapy developed asymptomatic nonsustained ventricular tachycardia, and this prompted a change in antiarrhythmic therapy. Both died suddenly of arrhythmia during substitute empiric antiarrhythmic drug therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Thrombolytic therapy in acute myocardial infarction--selected recent developments.

Thrombolytic therapy is the established treatment of choice for most eligible patients with acute myocardial infarction. Early initiation of treatment and early, complete and maintained patency of the infarct-related coronary artery are desirable, because these variables correlate with a reduction in mortality. As a consequence, considerable efforts have been undertaken to develop new pharmacological agents that serve these purposes. Among these, new plasminogen activators such as reteplase (r-PA), saruplase (scuPA), and staphylokinase are in clinical development, and DSPA (bat t-PA) and antibody-targeted plasminogen activators (ScuPA-59D8) have undergone extensive animal testing. Anticoagulants such as recombinant hirudin, hirulog, argatrobane, and Factor Xa inhibitors, as well as antiplatelet agents on the basis of monoclonal antibody 7E3 offer promise as adjunctive therapy to thrombolysis or to invasive intracoronary procedures.

Enzyme Precursors↗
PubMed2001

Basic science research on the urinary bladder and interstitial cystitis: new genetic approaches.

This article summarizes recent genetic research that promises to advance understanding of the functioning of the urinary bladder and further our knowledge about interstitial cystitis. Results reported at the Tenth International Research Symposium on Interstitial Cystitis and Bladder Research and in the current literature are presented. Three specific areas of genetic research are summarized: gene expression via DNA arrays, development of new animal models through transgenic or gene knockout approaches, and gene therapy. Advances in genetic research (specifically in gene therapy; development of new, genetically engineered mouse models; and study of gene expression using DNA array assays) will contribute to further understanding the functioning of the urinary bladder in health and disease.

Animals↗