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.

SourceResearch connectionFrom yearThrough year

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

At least 739 records · Page 41Linked to original sources

PubMed2004

Inhibition of tumor-associated fatty acid synthase activity enhances vinorelbine (Navelbine)-induced cytotoxicity and apoptotic cell death in human breast cancer cells.

The lipogenic enzyme fatty acid synthase (FAS) is differentially overexpressed and hyperactivated in a biologically aggressive subset of breast carcinomas and minimally in most normal adult tissues, rendering it an interesting target for anti-neoplastic therapy development. Current trends in the treatment of human breast cancer are with drug combinations that result in improved responses as well as the ability to use less toxic concentrations of the drugs. Here, we envisioned that combinations of conventional chemotherapeutic agents with novel compounds directed against breast cancer-associated FAS hyperactivity may provide increased efficacy over existing therapy for human breast cancer. Specifically, we examined the ability of the mycotoxin cerulenin, a potent and non-competitive inhibitor of FAS activity, to enhance the cytotoxic effects of vinorelbine (Navelbine), a derivative of vinca alkaloid that interferes with tubulin assembly and exhibits activity against metastatic breast cancer. SK-Br3, MCF-7 and MDA-MB-231 human breast cancer cell lines were employed as models of high, moderate and low levels of FAS ('cerulenin-target'), respectively. Combinations of cerulenin with vinorelbine were tested for synergism, additivity or antagonism using the isobologram and the median-effect plot (Chou-Talalay) analyses. Breast cancer cells were either simultaneously exposed to cerulenin and vinorelbine for 24 h or sequentially to cerulenin for 24 h followed by vinorelbine for 24 h. Concurrent exposure to cerulenin and vinorelbine resulted in synergistic interactions in MCF-7 and MDA-MB-231 cell lines, while additivity was found in SK-Br3 cells. Sequencing cerulenin followed by vinorelbine resulted in synergism for SK-Br3 and MDA-MB-231 cells, whereas it showed additive effects in MCF-7 cells. FAS activity blockade was found to synergistically enhance apoptosis-inducing activity of vinorelbine, as determined by an enzyme-linked immunosorbent assay for histone-associated DNA fragments. To the best of our knowledge this is the first study demonstrating that breast cancer-associated FAS is playing an active role in human breast cancer chemosensitivity. We suggest that pharmacological inhibition of FAS activity is a novel molecular approach to enhance the cytotoxic effects of existing chemotherapeutic agents in human breast cancer.

Antifungal Agents↗

PubMed2004

Roads from vaccines to therapies.

Over the past decade, we have demonstrated that various recombinant fragments of botulinum neurotoxin are highly immunogenic, stimulating notable levels of protective antibodies in mice, guinea pigs, and nonhuman primates. One of the fragments evaluated, the fragment C, is a potential next-generation vaccine candidate to replace the current pentavalent botulinum toxoid vaccine. Synthetic genes encoding the carboxyl-terminal regions (approximately 50 kDa) of toxin types A, B, C1, E, and F were expressed in Pichia pastoris, and manufacturing processes were developed for producing highly purified vaccines. These vaccines were shown to be safe, highly efficacious, stable, and amenable to high-level industrial production. Recombinant vaccines are now being produced in accordance with current Good Manufacturing Practices for use in future clinical trials. As our discovery-based program on vaccine development is diminishing, it is concurrently being replaced with a program focused on developing therapeutic interventions to botulism. Synthetic genes encoding the light chains of botulinum toxin have been expressed in Escherichia coli, and purified. These proteolytically active light chains are being used in high-throughput assays to screen for inhibitors of its catalytic activity. Other resources developed as part of the vaccine initiative, likewise, are finding utility in the quest to develop therapies for botulism.

Animals↗

PubMed1979

Immunotherapy in bee sting hypersensitivity. Bee venom versus wholebody extract.

Fifty-six patients with serologically confirmed bee sting hypersensitivity were treated for 1-3 years with either bee venom (BV) (31 patients) or wholebody extract (WBE) (25 per cent of re-exposed patients on BV-therapy showed a diminished reaction and 75% no reaction. Thirty-three per cent of re-exposed patients on WBE-therapy developed an unchanged or worse reaction, 42% a diminished reaction and 25% no reaction at all. An initial rise in BV-specific IgE was observed in BV-treated patients, whereas IgE levels after 1 year of treatment lay significantly below pretreatment values in both treatment groups. BV-specific IgG increased markedly in patients on BV-therapy and decreased slightly in those on WBE-therapy. The initial IgE increase induced by BV-therapy was insignificant in patients with high pretreatment levels of specific IgG-antibodies. Similarly, re-exposed patients with high BV-specific IgG showed no IgE increase, whereas a substantial rise in specific IgE was observed in those with low IgG. On the basis of clinical and serological results immunotherapy with BV is considered to be clearly superior to immunotherpy with WBE.

Adult↗

PubMed1990

Clinical experience with parenteral and oral ofloxacin in severe infections.

This study included 107 patients who were given ofloxacin at daily doses of 400-800 mg for 10 days to 12 months for treatment of a variety of infections. 77 patients were given ofloxacin orally and 30 received it intravenously. Infections treated were bronchopneumonia (29), chronic bronchitis with acute exacerbation (15), chronic osteomyelitis with exacerbation (20), soft tissue infections (13), complicated urinary tract infections (7), chronic prostatis with exacerbation (7), malignant external otitis (4), or other infections (12). Pathogens included Pseudomonas aeruginosa (39), Acinetobacter spp. (9), various Enterobacteriaceae (30), Haemophilus influenzae (26), pneumococci (1) and Staphylococcus aureus (4). MICs of ofloxacin ranged from less than 0.06-2 mg/l. Clinically, 69% of the patients were cured, 18% improved and 13% failed to respond. Bacteriologically, pathogens were eradicated in 70%, persisted in 16% and relapsed in 14%. Resistance during therapy developed almost exclusively in P. aeruginosa strains (17.9%). The following adverse reactions were reported: gastrointestinal disturbances (6), rash plus facial oedema (1), abnormal liver function tests (5) and leukopenia (1). It is concluded that ofloxacin is suitable for treatment of a variety of infections, ranging from serious life threatening infections in ICU patients to chronic ones that require prolonged therapy.

Administration, Oral↗

PubMed1989

Evaluation of the policy of empiric treatment of suspected Toxoplasma encephalitis in patients with the acquired immunodeficiency syndrome.

PURPOSE: This study was designed to measure response rates and survival in patients with acquired immunodeficiency syndrome (AIDS) and suspected Toxoplasma encephalitis treated empirically and in AIDS patients treated for biopsy-proven toxoplasmosis. PATIENTS AND METHODS: AIDS patients identified at Bellevue Hospital between August 1985 and May 1986, who had abnormal computed tomographic scans of the brain and who received empiric treatment for toxoplasmosis, constitute the empirically treated cohort. A cohort with biopsy-proven toxoplasmosis was identified from Bellevue Hospital neuropathology records spanning 1981 through 1986. Patient records were reviewed with a standardized data form, and tomograms were evaluated by neuroradiologists unaware of the identity of the scans. Survival analysis was performed by the product limit method. RESULTS: Of 38 empirically treated patients, 26 responded clinically and radiographically within four weeks of initiation of therapy. Four of nine patients who underwent biopsy responded to treatment. There was no difference in these response rates (68% versus 44%, p = 0.24). The median survival of the empirically treated responders, from first diagnosis of AIDS to last follow-up, was 422 days. Among the 30 responders, five patients discontinued therapy and four of them had relapses. No relapses occurred in the 25 patients who continued full-dose therapy indefinitely (p = 0.0004). Sixteen of 30 patients (53%) receiving continuous therapy developed toxicity, which required a change in medication. There was no difference in the survival of patients who continued to receive sulfadiazine and pyrimethamine compared with those in whom clindamycin was substituted for sulfadiazine (median, 311 days versus 422 days, p = 0.25). CONCLUSION: A policy of empiric treatment of suspected Toxoplasma encephalitis is satisfactory, and patients who respond to such therapy and continue to take full therapeutic doses of anti-Toxoplasma drugs have relatively long survivals.

Acquired Immunodeficiency Syndrome↗

PubMed2001

[Risk of deep infection in first-intention total hip replacement. Evaluation concerning a continuous series of 790 cases].

OBJECTIVE: Deep infections of the operative site is a rare but serious complication of first intention total hip arthroplasties. French data on infections are sparse. We studied the incidence, characteristics and potential risk factors for these infections in a consecutive series of 790 total hip arthroplasties performed as first intention implantations in a University Hospital in France. PATIENTS AND METHODS: All patients undergoing first intention total hip arthroplasty surgery between November 1995 and May 1999 were included in this study. Demographic, clinical, therapeutic and surgical data were collected. Deep infection was defined as proven presence of microorganisms in at least two preoperative samples during revision surgery. Patients were followed for 1 month to 4 years. Potential risk factors were identified with univariate analysis. Chi square and exact Fisher test were used. RESULTS: The overall incidence of deep infections was 1.11 per 100 implantations (95% CI 0.84-2.70). Delay to development ranged from 14 days to 32 months. Eleven infections were proven within the first year and 3 after one year. Two risk factors were identified: absence of systemic antibiotic prophylaxis (RR = 4.74, p = 0.03) and drainage discharge after 48 hours (RR = 3.62, p = 0.02). Other variables associated with infection with a relative risk greater than 2 were obesity, corticosteroid therapy, development of a hematoma, or difficult postoperative wound healing. CONCLUSION: The incidence observed in this series is slightly higher than generally reported in the world literature. It would be important to write an antibiotic prophylaxis protocol with prescription of systemic antibiotics for all operated patients in order to reduce this incidence. Other measures that could improve the quality of care should also be taken: re-evaluation of preoperative skin preparation protocols, systematic screening of patients carrying Staphylococcus aureus before implantation and proper care for these patients.

Adult↗

PubMedDate not supplied

[Cell therapy and other neuroregenerative strategies in Parkinson's disease (I)].

OBJECTIVE: To review, from a mainly clinical standpoint, the different strategies applied to regenerate or restore the nigrostriatal dopaminergic system in Parkinson's disease. This first part focuses on the results of adrenal medulla and human fetal mesencephalic transplants, and a second part will address transplants of other cell types, administration of trophic factors, and gene therapy. DEVELOPMENT: Adrenal medulla transplants were abandoned because of their inconsistent results and high morbidity. Although fetal mesencephalic transplantation can produce long-term restoration of striatal dopamine deficiency, this neurochemical effect is clinically inadequate in presence of progressive neuronal loss. Other strategies with similar 'dopaminergic' action mechanism are not a therapeutic option in this setting. CONCLUSIONS: The objective of neuroregenerative therapy for Parkinson's disease should include trophic restoration of damaged neuronal systems, since improvement in striatal dopaminergic function is not sufficient. After the recent failure of the direct (intraventricular or intraputaminal) administration of glial cell line-derived neurotrophic factor (GDNF), attention of researchers has focused on indirect methods, including transplantation of GDNF-producing cells (carotid body cell aggregates or different genetically modified cells, including stem cells), and in vivo gene therapy.

Adrenal Medulla↗

PubMed1995

[Immunoglobulins--merely expensive or also useful?].

About 15 years ago, treatment with intravenous immune globulin (IVIG) for primary immunodeficiency diseases was introduced. The concept of replacement of deficient circulating antibodies to prevent infections in these patients subsequently proved to be beneficial. Up-to-date IVIG therapy is considered to be the treatment of choice in many primary or secondary immunodeficiency states. The observation of a significant increase in the platelet count in patients with agammaglobulinemia and severe thrombocytopenia after IVIG therapy developed interest in possible modulatory effects of IVIG on the immune system. Although the mode of action of IVIG in autoimmune diseases is not completely understood, therapeutic benefit has been shown in some diseases. It has to be stated that IVIG in autoimmune diseases are rarely first therapeutic choice; however, IVIG might be indicated in patients where conventional and cheaper therapy has failed. This review summarizes the status of IVIG therapy in primary and secondary immunodeficiency states and possible indications in autoimmune diseases.

Agammaglobulinemia↗

PubMed2005

Opsoclonus-myoclonus in an HIV-infected child on antiretroviral therapy--possible immune reconstitution inflammatory syndrome.

The exact immunopathogenesis and neuroanatomical localization of opsoclonus-myoclonus ataxia syndrome remains unclear. We describe a 1 year 9 month old girl who, shortly after commencement of highly active antiretroviral therapy developed opsoclonus-myoclonus syndrome and subsequently died of disseminated cytomegalovirus infection. We postulate on the etiological factors that may have played a role in the disease pathogenesis of the patient's opsoclonus-myoclonus ataxia. Immune reconstitution inflammatory syndrome was considered the most likely because of the initial CD4 depletion and the onset of symptoms shortly after initiation of antiretroviral therapy. Single photon emission computed tomography (SPECT) proved helpful by localizing the area of dysfunction to the cerebellar vermis.

Adrenocorticotropic Hormone↗

PubMed1992

Fluoxetine-induced psoriasis.

BACKGROUND: A number of medications have been reported to induce psoriasis. We report two cases of fluoxetine-related psoriasis and discuss similarities between lithium-, trazodone hydrochloride-, and fluoxetine-induced psoriasis. OBSERVATIONS: Two women being treated for depression with fluoxetine developed psoriasis after 6 and 12 months' exposure. This time frame is clinically similar to that observed with lithium-induced psoriasis. CONCLUSIONS: The occurrence of lithium- and fluoxetine-induced psoriasis may not be random. Both drugs modulate serotonergic function, a factor that may contribute to the pathophysiology of psoriasis. If a patient on acute or long-term fluoxetine therapy develops psoriasis, the drug should be considered as a possible etiologic agent.

Adult↗

PubMedDate not supplied

Effect of duration of chronic peritoneal dialysis therapy on the development of peritonitis.

OBJECTIVE: Long-term chronic peritoneal dialysis (CPD) therapy has been associated with alterations in peritoneal membrane structure and peritoneal macrophage function. We thus reviewed our experience with the development of peritonitis among patients maintained on CPD therapy for various time periods to determine if the spectrum of organisms, rates of peritonitis, and outcome changed with the duration of CPD therapy. SETTING AND PATIENTS: Patients maintained on CPD therapy in our out-patient unit in New Haven, Connecticut. DESIGN: Retrospective review of the charts of patients maintained on CPD therapy (HomeChoice Cycler or Ultrabag, Baxter, McGaw Park, IL, U.S.A.) between 1 January 1997 and 31 March 1998. These patients were divided into three groups: group 1, patients maintained on CPD therapy < or = 12 months; group 2, patients maintained on CPD therapy for 13-36 months; and group 3, patients maintained on CPD therapy for > or = 37 months. RESULTS: The study included 256 patients: 101 patients in group 1, 110 patients in group 2, and 45 patients in group 3. All groups of patients were similar in age. There were significantly fewer Caucasians and fewer males in group 3 in comparison to groups 1 and 2. The incidence of diabetes mellitus, coronary artery disease, and peripheral vascular disease was significantly lower among patients in group 3 in comparison to groups 1 and 2. There were 155 episodes of peritonitis during the study period for an overall rate of 1 episode in 18.7 patient-months. The overall, gram-positive, and gram-negative rates of peritonitis were not significantly different among the patients in groups 1, 2, and 3. There were more episodes of Staphylococcus aureus peritonitis among patients in group 3 in comparison to group 2 (1 episode in 59.6 vs 1 episode in 280.2 patient-months, respectively). Two weeks after the development of peritonitis, 94.6% of the patients in group 3 continued CPD therapy, while 79.4% of the patients in group 1 continued CPD therapy (p < 0.05). No patient in group 3 transferred to hemodialysis, while 10.3% and 8.2% of the patients in groups 1 and 2 transferred to hemodialysis (p < 0.05). The death rate 2 weeks after the onset of peritonitis was 10.3%, 9.8%, and 5.4% in groups 1, 2, and 3, respectively (p = NS). CONCLUSIONS: Despite the immunological and morphological changes that occur in the peritoneal cavity with increased time on CPD therapy, there was no difference in the overall, gram-positive, or gram-negative rates of peritonitis for patients maintained on CPD therapy for various time periods. Patients in group 3 continued CPD therapy more often than did patients in group 1. Patients in group 3 transferred to hemodialysis less often than did the remaining patients in the study period. The incidence of death was not significantly different for the three groups of patients.

Female↗

PubMed1985

Prolactin cell carcinoma of the pituitary. Clinicopathologic, immunohistochemical, and ultrastructural study of a case with cranial and extracranial metastases.

A patient with a primary adenohypophyseal neoplasm who had a long course marked by multiple surgical resections, radiation therapy, and high-dose dopamine agonist therapy developed local invasion as well as cranial and extracranial osseous metastatic lesions. The serum prolactin levels were greatly elevated, and immunohistochemical studies demonstrated prolactin in the cytoplasm of primary and metastatic tumor cells. Ultrastructural features of lactotrophic differentiation, including misplaced granule exocytosis, were observed. This is the third reported case of prolactin cell carcinoma that metastasized despite high-dose dopamine agonist therapy. Analysis of the patient's serum prolactin showed no abnormality in the chromatographic profile of biologic activity.

Biological Assay↗

PubMed2005

Seizure-related factors and non-verbal intelligence in children with epilepsy. A population-based study from Western Norway.

PURPOSE: To study the relationship between seizure-related factors, non-verbal intelligence, and socio-economic status (SES) in a population-based sample of children with epilepsy. METHODS: The latest ILAE International classifications of epileptic seizures and syndromes were used to classify seizure types and epileptic syndromes in all 6-12 year old children (N=198) with epilepsy in Hordaland County, Norway. The children had neuropediatric and EEG examinations. Of the 198 patients, demographic characteristics were collected on 183 who participated in psychological studies including Raven matrices. 126 healthy controls underwent the same testing. Severe non-verbal problems (SNVP) were defined as a Raven score at or <10th percentile. RESULTS: Children with epilepsy were highly over-represented in the lowest Raven percentile group, whereas controls were highly over-represented in the higher percentile groups. SNVP were present in 43% of children with epilepsy and 3% of controls. These problems were especially common in children with remote symptomatic epilepsy aetiology, undetermined epilepsy syndromes, myoclonic seizures, early seizure debut, high seizure frequency and in children with polytherapy. Seizure-related characteristics that were not usually associated with SNVP were idiopathic epilepsies, localization related (LR) cryptogenic epilepsies, absence and simple partial seizures, and a late debut of epilepsy. Adjusting for socio-economic status factors did not significantly change results. CONCLUSIONS: In childhood epilepsy various seizure-related factors, but not SES factors, were associated with the presence or absence of SNVP. Such deficits may be especially common in children with remote symptomatic epilepsy aetiology and in complex and therapy resistant epilepsies. Low frequencies of SNVP may be found in children with idiopathic and LR cryptogenic epilepsy syndromes, simple partial or absence seizures and a late epilepsy debut. Our study contributes to an overall picture of cognitive function and its relation to central seizure characteristics in a childhood epilepsy population and can be useful for the follow-up team in developing therapy strategies that meet the individual needs of the child with epilepsy.

Adolescent↗

PubMed1998

Treatment of pemphigus with gold.

BACKGROUND: Although gold has been reported to be useful in treating pemphigus vulgaris, its use has waned in recent years because of concerns regarding efficacy and toxicity. OBJECTIVE: To review 26 patients with pemphigus who were treated with intramuscular gold over a 10-year period. RESULTS: Gold was effective in 62% of patients as a primary treatment for pemphigus or as a steroid-sparing agent. An average of 3 months of therapy was required before the daily prednisone dosage could be halved. Four patients were free of disease and stopped receiving all therapy at the conclusion of the study. Toxic effects due to gold therapy developed in 42% of patients and all adverse effects resolved with its cessation. CONCLUSIONS: While toxic effects limit the use of gold in many patients with pemphigus, it may be effective in treating a large percentage of patients who otherwise are unable to reduce their steroid requirement. Because of its delayed onset of action, patients treated with gold usually require systemic steroids when therapy is initiated. Controlled, prospective trials are needed to further evaluate the efficacy of gold and its potential steroid-sparing effects.

Adult↗

PubMed2005

Prophylaxis and treatment of bacterial infections: do we need new strategies?

Bacterial infections in patients with hematologic malignancies still represent a severe and life-treating problem. Several observational studies during the last decade have revealed that neutropenic patients with fever are a heterogeneous population with various differences regarding response to initial therapy, development of serious complications and mortality. The role of neutropenia as main risk factor for infections in hematologic patients and the definition of different level of risk related to neutrophils count and duration of neutropenia have been extensively studied and different categories of patients based on the risk of infection, mostly the condition of neutropenia, have been clearly defined. The strategies on antimicrobial therapy and supportive care in hematologic patients need to be continuously assessed, in fact new conditions favouring the occurrence of infectious complications in patients with hematologic malignancies have progressively emerged. The use of oral prophylactic antibiotics in neutropenic cancer patients is still a matter of debate. Before 2005, several trials showed how the prevention of infection can be extremely important in this setting of patients but none was conclusive. In 2005 two meta-analysis and two large randomized clinical trials gave new evidence that antibacterial prophylaxis can reduce in neutropenic patients several important outcomes including mortality. The use of the empiric antibacterial therapy represents the cornerstone of the antimicrobial strategies in the febrile neutropenic patients leading, over the span of 20 years, to a dramatic decrease of deaths: Actually beta-lactam monotherapy is commonly used for the empiric treatment of febrile neutropenia. Recently, large randomized clinical trials and meta-analysis showed that the addition of an aminoglycoside and/or a glycopeptides results in a more favourable outcome only in selected severe infections. The use of antibiotics should be prudent and safe also in neutropenic hematologic patients to prevent emergence of microbial resistance, to save costs, to reduce toxicity. For this reasons, according to the evidence, antibacterial prophylaxis should be restricted to high risk hematologic patients and empiric parenteral antibiotic monotherapy should be recommended in case of febrile neutropenia limiting the use of amynoglicosides and glycopeptides. In the next future, a major effort should be made to state in hematologic patients new risk factors which could more accurately define subgroups for targeted anti-infective strategies.

Bacterial Infections↗

PubMed1993

[Clinical profile and course of paroxysmal nocturnal hemoglobinuria].

PURPOSE: To evaluate the clinical characteristics, laboratory findings, course, treatment and survival of a series of patients with PNH. PATIENTS AND METHODS: The clinical records of 21 patients diagnosed of PNH in the La Fe University Hospital between 1970 and July 1991 were revised. Positivity to Ham's and sucrose tests was the major diagnostic criterion. Haemolysis was studied by means of reticulocyte count, unconjugated bilirubin, LDH levels, haptoglobin, serum iron, and haemosiderinuria. The survival analysis was performed in accordance with Kaplan and Meier. RESULTS: The median age in the group was 38 years (range: 18-72 years) and the M/F ratio was 11/10. The commonest symptoms at onset were weakness (76%), dark urine (47%), jaundice (33%), and purpura (24%). All the patients had anaemia, six of them (28%) presenting with aplastic anaemia. The complications most frequently seen included thrombosis (documented in 7 cases, clinically suspected in 6 others), infection (6 cases) and haemorrhage (6 cases). One patient developed aplastic anaemia after 16 years of follow-up, and another one had AML. None of the patients with PNH-associated aplastic anaemia developed thrombosis. The incidence of severe cytopenia was: Hb < 80 g/L, 62%; platelet count < or = 20 x 10(9)/L, 29%, and white cell count < or = 2 x 10(9)/L, 14%. The haemolysis-related findings were as follows: unconjugated hyperbilirubinemia, 100%; haemosiderinuria, 87%; decreased haptoglobin, 80%. Transfusion support consisted of washed red cells (total amount, 1,684 units) and platelets (137 units). A female patient with anticoagulant therapy developed haemolysis after non-isogroup plasma transfusion. Five patients required no transfusions. One patient was subjected to splenectomy and other underwent a successful bone-marrow transplant. The cause of death was related to PNH in three of the five patients who had died when this study was finished (mesenteric thrombosis, subcapsular haematoma of the liver and AML). The actuarial survival at 10 years was 68%. CONCLUSIONS: 1) The incidence of PNH is very low in our experience, excessive delay in diagnosis being the rule, as in other reported series. 2) Early anti-thrombotic treatment should be carried out in PNH whenever severe thrombocytopenia is not associated. 3) Allogeneic BMT is the only curative treatment.

Adolescent↗

PubMed2006

Once daily, oral, outpatient quinolone monotherapy for low-risk cancer patients with fever and neutropenia: a pilot study of 40 patients based on validated risk-prediction rules.

BACKGROUND: The objective of this study was to assess the feasibility of empiric, oral, outpatient quinolone monotherapy in 40 adult patients with fever and neutropenia who were at low risk for serious medical complications. METHODS: Patients with breast cancer or sarcoma who presented with fever and neutropenia and were identified as low risk received empiric, oral, quinolone monotherapy (gatifloxacin at a dose of 400 mg once daily). Patients who had a significant source/focus of infection on presentation were excluded. After an initial observation period of 4 to 8 hours in the emergency center, the remainder of their management was ambulatory. Patients were evaluated for response to therapy, development of complications and/or the need for hospital admission, and drug-related adverse events. RESULTS: Three of 43 patients studied were ineligible medically because of the presence of Common Toxicity Criteria (version 3.0) Grade>2 mucositis. Of the 40 eligible patients, 38 patients (95%) responded to gatifloxacin monotherapy, although 1 patient requested hospital admission (92% response for ambulatory management). The mean duration of therapy was 7 days, and the median number of days from enrollment to defervescence was 4 days. There were no serious medical complications, no drug-related adverse events, and no deaths on study or during 30 days of follow-up. CONCLUSIONS: The results from this study indicated that outpatient quinolone monotherapy in low-risk febrile neutropenic patients is safe, effective, and well received. These conclusions need to be validated in a randomized trial.

Administration, Oral↗

PubMed1993

Analysis of production, purification, and cytolytic potential of bi-specific antibodies reactive with ovarian-carcinoma-associated antigens and the T-cell antigen CD3.

OV-TL3 and MOv 18 MAbs, due to their restricted specificity, have been successfully used to visualize ovarian cancer in patients and might therefore be used to develop therapies for ovarian cancer. The bi-specific MAbs alpha T3/OC2 and alpha OC/TR (both being combinations of MOv18 and alpha CD3) have been shown to lyse ovarian tumor cells in vitro. To evaluate the relative merits of MOv18/CD3 and OV-TL 3/CD3, the present study was undertaken in which the bi-specific MAbs alpha T3/OC2 and alpha OC/TR, and a newly developed bi-specific MAb, OV-TL 3/CD3, were highly purified and compared for specificity, stability, purification and cytolytic potential. The dual specificity of the hybrid-hybridoma supernatants was analyzed by immunohistochemistry, and by testing bi-specific MAb-mediated cytotoxicity against relevant target cells in the presence of effector cells. Stability testing of bi-specific MAb-producing hybridomas showed that, after sub-cloning, clones stably produced up to 40% bi-specific MAb even after prolonged in vitro culture. The purification of the bi-specific fractions was performed with protein A and by ion-exchange high-pressure liquid chromatography, depending on the sub-class combination of the bi-specific MAb. The purified bi-specific MAbs were tested for their ability to mediate target-cell lysis with the use of cytotoxic T-cell clones and activated peripheral-blood lymphocytes. The purified alpha T3/OC2, alpha OC/TR, and OV-TL3/CD3 were all able to mediate highly specific lysis of various ovarian-carcinoma cell lines. No correlation was found between the level of antigen expression and bi-specific MAb-mediated cytolysis.

Antibodies, Monoclonal↗