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At least 1,729 records · Page 96Linked to original sources
PubMed2002

Histomorphometric analysis of dentinal bridge formation and pulpal inflammation.

OBJECTIVE: The purpose of this study was to evaluate pulpal responses to the use of four resin composite materials as direct pulp capping agents. The importance and effects of individual pulp capping variables are not well understood; consequently histomorphometric analysis was used to analyze these variables. METHOD AND MATERIALS: Two hundred fifty standardized pulp-exposed cavities were prepared in nonhuman primate teeth. Exposed pulps were capped with calcium hydroxide and multistep and self-etching primer resin composites. Teeth were collected from 3 to 60 days to observe pulpal reactions. Following perfusion fixation, tissues were demineralized, sectioned, stained, and histomorphometrically measured. Bridge area, diameter of pulpal exposure, and cavity floor width were measured. Tunnel defects, operative debris, and pulpal inflammation were graded according to defined criteria. RESULTS: The variables correlated to dentinal bridge area were, in decreasing order of significance, time elapsed since exposure, diameter of pulpal exposure, pulp capping material, and tunnel defects. The variables correlated to pulpal inflammation were the type and curing of pulp capping material. Other variables were not statistically significant. CONCLUSION: Pulp capping with resin composite materials provided acceptable pulpal inflammatory and dentinal bridge repair responses, comparable with those of calcium hydroxide. Although resin composites are promising as direct pulp capping agents, further investigations are required to optimize their application protocols to reduce the penetration of potentially cytotoxic monomers into pulpal tissue.

Acid Etching, Dental↗
PubMed2002

A dyspnea evaluation protocol for respiratory therapists: a feasibility study.

PURPOSE: We tested the feasibility of incorporating a dyspnea evaluation protocol into bedside assessments routinely performed by respiratory therapists (RTs) on mechanically ventilated patients at a university teaching hospital. METHODS: A dyspnea assessment protocol was incorporated into the RT assessments performed at 4-hour intervals on endotracheally intubated, mechanically ventilated patients in our medical and surgical intensive care units. RTs were asked to inquire of all responsive patients: "Are you feeling short of breath right now?" and, if yes, "Is your shortness of breath mild, moderate, or severe?" We analyzed 324 consecutive patient ventilator flow sheets from 77 medical and 161 surgical intensive care unit patients. RESULTS: Dyspnea scores were recorded during 1,870 of 2,539 scheduled RT patient assessments. The protocol compliance rate was 74%. Patients were sufficiently responsive to answer the protocol questions during 32.1% of the bedside assessments. Dyspnea was recorded in 11% (67/600) of those encounters. Dyspnea was described most often as mild. CONCLUSIONS: Initial implementation of a dyspnea evaluation protocol was moderately successful in prompting RTs to ask mechanically ventilated patients whether they felt short of breath during scheduled bedside visits. A rapid bedside evaluation for dyspnea may prove useful in evaluating the effect on patient distress of implementing protocols designed to optimize ventilator settings or the use of sedating drugs during mechanical ventilation. By this approach RTs may also be able to promote a patient-centered approach to managing respiratory failure in the intensive care unit.

Dyspnea↗
PubMed2002

[How to use contrast material in multislice CT examinations].

Since the introduction of multislice CT in the clinical field, the acquisition time for helical CT becomes very short. As a result, contrast material administration becomes more difficult but at the same time offers new opportunities. Scan protocol should be optimized depending on the organ. To reach the best contrast enhancement, several different approached have been proposed. In general, higher injection rate result in higher level of arterial enhancement suitable for CT angiography. Scan timing should be optimized using bolus triggering or test injection technique. Sufficient amount of contrast material should be used in parenchymal imaging including liver and pancreas. For venous imaging including portal vein, sufficient contrast medium is also required to obtain diagnostic 3D imaging. Multislice CT may be beneficial in CTAP and CTHA examinations. In chest CT examinations, the amount of contrast material relative to single slice helical CT can be reduced. The overall quantity, flow rate and type of contrast medium still need to be optimized in further studies.

Angiography↗
PubMed2003

[Development of gene therapy for hematopoietic stem cell using viral vectors].

Hematopoietic stem cells (HSC) are attractive targets for gene therapy of inherited and acquired disorders in hematopoietic system in that they possess the properties of self-renewal, proliferation, and multi-lineage differentiation. For successful gene therapy, the viral vector-mediated gene addition strategy has two essential prerequisites: 1) the efficient transfer of therapeutic gene into HSC; 2) the long-term and stable expression of the transgene at therapeutic levels. The oncoretrovirus-derived vectors are best understood and most widely investigated. Recent successful cases of gene therapy for severe combined immunodeficiency due to adenosine deaminase or gamma c chain deficiencies have provided strong evidences that retrovirus-mediated gene transfer into HSC will work in clinical treatment. While these results are encouraging, some obstacles remain to be circumvented including low efficiency of gene transfer and gene silencing in retroviral vector system. The therapeutic gene can be efficiently introduced into HSC by HIV-1-based lentiviral vector due to its capability to infect the quiescent cells. A variety of preclinical studies are now conducted and a number of valuable results highlight the efficacy of lentiviral-mediated gene transfer into HSC. However, the potential value of lentiviral vectors in human gene therapy remains to be demonstrated. Adeno-associated virus vector is an alternative to retroviral and lentiviral vectors. This review summarizes the characteristics of integrating vectors, the improved HSC transduction protocols, and the optimized gene expression strategies and outlines the important advances of preclinical and clinical trials in hematopoietic stem cell gene therapy.

Adenoviridae↗
PubMed1992

[Intravenous immunoglobulins in hematologic therapy].

The use of intravenous immunoglobulin (IgIV) increased in the last ten years. IgIV are used in three different groups of haematologic pathologies. The first group is formed by the immunodeficiencies: primaries (those that started the use of IgIV) and secondaries (from immunosuppressive agents and from deficit accessories of Ig). The second group is that of autoimmunity of the blood corpuscular elements (ITP, autoimmune neutrocytopenia and autoimmune haemolytic anaemias). The third group is represented by thrombotic thrombocytopenic purpura. The right protocol and the optimal formulas of the dosages of IgIV are still to be tested. The same applies to its action mechanisms and its potential utilization in other diseases.

Autoimmune Diseases↗
PubMed1992

First principles of fast spin echo.

Fast spin echo (FSE), a variant of the rapid acquisition with refocused echoes pulse sequence, is now being widely considered as an alternative to conventional spin echo for proton density and T2-weighted imaging. Although the medical experience with this sequence is relatively limited, relevant aspects of the technique have been well understood in the context of spectroscopic applications for many years. This article attempts to portray the subject in an appropriate historical context. Such a viewpoint promotes a deeper understanding of the artifacts, determinants of contrast, and future evolution of FSE. Hopefully, this may not only be of benefit in the design of optimal clinical imaging protocols for current state of the art but may also be of use in fashioning the criteria by which new developments in this field may be judged.

Artifacts↗
PubMed2004

[Neuroprotection in brain ischemia--doubts and hopes].

In ischaemic stroke the two major potential therapeutic strategies are aimed at either improving cerebral blood flow or directly interacting with the cytotoxic cascade--a large body of evidence gained from animal studies is in support of them. In clinical trials direct neuroprotection by blocking the neurotoxic cascade remained ineffective, although there are several clinical trials still in progress. We summarize the experimental data and present the results of clinical trials and also discuss why so many drugs, which were effective in animal studies, failed in human trials. It is emphasized, that 1. in most animal studies the reduction of infarct size, i.e. the amount of saved penumbral tissue, was the outcome measure, whereas neurological function remained unassessed; 2. the recovery of intellectual performance and higher cortical functions are of major importance in the future quality of life in stroke victims; however, it is impossible to examine these parameters appropriately in animal studies; 3. in many clinical trials the patient population was rather heterogenous and low in number, the study protocol was not optimal and the critical analysis of the subacute and chronic phase was lacking or insufficient. We present the major experimental stroke models, discuss their similarities, differences and limitations as compared to the human pathophysiological processes. The pitfalls of extrapolating data from animal studies to clinical practice are also summarized. The complex network of functional and morphological intercellular connections, the long timescale of neurotoxic and reparative events and the lessons learned from clinical trials suggest, that the use of drug combinations (therapeutic cocktails) targeting multiple steps of the neurotoxic cascade would hopefully result in more effective treatment of ischaemic stroke. Strategies to facilitate brain plasticity and regeneration is an additional promising tool to enhance recovery in brain ischaemia.

Animals↗
PubMed2004

Bexarotene: new preparation. Cutaneous lymphoma: too many adverse effects.

(1) Existing treatments for cutaneous T cell lymphoma (topical agents, chemotherapy, photopheresis, interferon alfa) have cosmetic benefits but no impact on survival. (2) Bexarotene, a synthetic retinoid, is approved for the treatment of adults with advanced-stage cutaneous lymphoma refractory to at least one systemic treatment. (3) Two non comparative trials included patients who were refractory or in relapse after various systemic treatments: one included 58 patients at an early stage of the disease, and the other 94 patients at an advanced stage. The evidence from these trials is weak for several reasons such as the lack of a standard endpoint for efficacy and numerous protocol modifications. The optimal dose of bexarotene is unknown. No comparative trials are available, and indirect comparisons are often misleading. (4) Nearly all patients treated with bexarotene suffer adverse effects, which can include hyperlipidemia (risk of pancreatitis), hypothyroidism, and haematological reactions (leukopenia, anemia). There is also an unconfirmed risk of cataract. (5) In practice, bexarotene is a highly toxic drug with uncertain efficacy, and there is no reason to prescribe it. Bexarotene should never have been authorised on the basis of such a bad evaluation.

Administration, Oral↗
PubMed2005

[Primary treatment of advanced Hodgkin's disease].

Primary treatment of advanced Hodgkin's disease. Hodgkin's disease is one of the few malignant diseases that can be cured even in an advanced stage in the majority of cases. By employing a polychemotherapy containing anthracyclines, a long remission and recovery can be achieved in 60-70% of the patients. At present the standard treatment is ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) scheme for the following reasons: besides good treatment results early side effects are more favourable; sterility and secondary acute leukemia present themselves less often than by employing regimens containing alkylating agents. Unfortunately, some of the patients do not react properly to the treatment and about one third of the patients who are in remission following primary treatment will relapse at a later stage. The main goal is now to further improve treatment (recovery) results without an increase, or even a decrease of early or late side effects. Awareness of prognostic factors should lead to the employment of a less intensive but not toxic therapy in patients with good prognosis to prevent overtreatment, while in cases with bad prognosis a more effective regimen is needed (even for the price of expected complications). The latest meta-analysis on the subject has shown that--similarly to sequential high dose therapy--the addition of radiotherapy to an effective chemotherapy does not seem to prolong the survival of patients. Despite the excellent therapeutic results achieved by the many new "intensive" chemotherapies, there is unfortunately no optimal therapy or protocol available today. The multicentre analysis to confirm these results and to compare them with standard scheme is still under way. It is to be hoped that risk adapted management for advanced stage Hodgkin's disease will also be available soon.

Age Factors↗
PubMed2006

Tolerance and efficacy of interferon-alpha in hemodialysis patients in Tripoli.

A prospective non-randomized study was conducted at the Department of Infectious Diseases at Tripoli Medical Center. We evaluated the tolerance and efficacy of interferon-alpha (IFN) monotherapy in our hemodialysis (HD) patients with chronic hepatitis C virus (HCV) infection. Patients with evidence of active viral infection i.e. positive polymerase chain reaction (PCR) results and who were potential transplant candidates were included in the study. They received three million units of IFN-alpha, administered subcutaneously, three times a week for 12 months. The treatment was discontinued in 12 out of the 35 treated patients (i.e drop out rate 34.2%). Among the 23 patients who completed the treatment course, 14 (60.8%) became PCR negative, and by the end of eighteen months, nine of the patients maintained PCR negativity (39%). Thus, a sustained virological response was observed in nine (25.7%) of the 35 enrolled patients. Our study suggests that the efficacy of IFN-alpha in our patients was less than anticipated and the tolerance to the drug was poor. However, studies involving larger numbers of patients are required to optimize the treatment protocol.

Adolescent↗
PubMed1990

A novel photoaffinity ligand for the phencyclidine site of the N-methyl-D-aspartate receptor labels a Mr 120,000 polypeptide.

A radiolabeled photoaffinity ligand has been developed for the N-methyl-D-aspartate (NMDA)-preferring excitatory amino acid receptor complex. [3H]3-Azido-(5S, 10R)(+)-5-methyl-10,11-dihydro-5H- dibenzo[a,d]cyclohepten-5,10-imine [3H]3-azido-MK-801 demonstrated nearly identical affinity, density of binding sites, selectivity, pH sensitivity, and pharmacological profile in reversible binding assays with guinea pig brain homogenates to those displayed by its parent compound, MK-801. When employed in a photo-labeling protocol designed to optimize specific incorporation, [3H]3-azido-MK-801 labeled a single protein band which migrated in sodium dodecyl sulfate-polyacrylamide gels with Mr = 120,000. Incorporation of tritium into this band was completely inhibited when homogenates and [3H]3-azido-MK-801 were coincubated with 10 microM phencyclidine. These data suggest that the phencyclidine site of the NMDA receptor complex is at least in part comprised of a Mr = 120,000 polypeptide.

Affinity Labels↗
PubMed1987

Rationale and strategies for chemoprevention of cancer in humans.

The potential for chemical intervention (chemoprevention) as a means of halting or delaying the process of carcinogenesis is assessed as a strategy for reducing the incidence of human cancer. The process of carcinogenesis is dissected into its constituent steps, thereby exposing sites for intervention. These sites are then critically discussed with regard to the existence of chemicals active at these sites using data gained from the laboratory and from epidemiological studies, intrinsic problems or advantages associated with intervention at specific sites in the carcinogenic process, and practical aspects of intervention in humans. The design and potential long-term positive and negative consequences of chemoprevention clinical trials are critically discussed, with the objective of exposing the major differences that exist between clinical trials in cancer chemoprevention and those in cancer chemotherapy. Results of completed prevention trials and details of ongoing trials are presented and discussed. Based on the laboratory, epidemiological, and clinical evidence presented, it is concluded that chemoprevention offers excellent prospects as a means of reducing cancer incidence. Among currently available agents, the retinoids possess the best combination of properties. However, much more research is needed to optimize drugs and protocols and to develop interim end points for assessing response. The authors finally caution that overambitious claims for the prospects for chemoprevention may lead to reduced emphasis on the need for changes in life-style (principally in smoking and diet) that are viewed as having the greatest potential for reducing cancer incidence.

Anti-Inflammatory Agents↗
PubMed1988

Platinum-radiation interactions.

The important chemotherapeutic agent cisplatin is currently being combined with radiation therapy (RT) in clinical protocols intended to exploit the potential for this drug to potentiate radiation-induced tumor cell kill. This paper reviews the reports from preclinical studies leading to the design of combined modality protocols and describes the effects produced when platinum complexes are combined with RT. Two interactions that are receiving considerable attention since they might produce an improved therapeutic ratio are the radiosensitization of hypoxic cells and post-RT potentiation of cell kill. This latter effect might include the inhibition of recovery from RT-induced potentially lethal or sublethal damage. However, platinum-radiation interactions are complex and probably include several mechanisms that are unknown at this time. The potential for platinum complexes will be especially promising if results of ongoing phase III combined modality trials show them to be efficacious, since it is unlikely that current protocol designs are optimal. Furthermore, second-generation platinum analogs or other metal complexes designed as potentiators of RT may prove to be more interactive with RT.

Animals↗
PubMed1985

Cyclosporin A in marrow transplantation for leukemia and aplastic anemia.

A total of 29 consecutive patients with leukemia or aplastic anemia who received an HLA-identical marrow graft were given cyclosporin A (CyA) to prevent graft-versus-host disease (GvHD). These patients were compared with an historic group of 25 similar patients with leukemia or AA given methotrexate (MTX) for GvHD prophylaxis at this institution. Engraftment was faster in patients given CyA when compared with MTX patients, with less days of granulocytopenia (P = 0.04), a shorter interval before reaching a platelet count of 70 X 10(9)/l (P = 0.04), fewer major infections (P = 0.01), and fewer days on intravenous antibiotics (P = 0.02). There were no graft failures in CyA patients compared with four of 25 in MTX patients (P = 0.01). Early mortality was lower in CyA patients but not significantly (P = 0.06). The incidence of pulmonary complications was comparable, five of 29 and seven of 25 in CyA and MTX patients, respectively, but the clinical features of such complications differed. Interstitial pneumonia developing after day 30 was seen in MTX patients, whereas an acute respiratory distress syndrome developing between day +8 and day +18 was seen in CyA patients. Acute GvHD was less severe in CyA patients (P = 0.04), but chronic GvHD was comparable (P = 0.3). The actual one-year survival is currently 72% and 52% in CyA and MTX patients, respectively (P = 0.1). Although our initial experience with CyA is encouraging with regard to engraftment and acute GvHD, optimization of CyA protocols will probably be needed for it to be proven as having a definite advantage over MTX.

Adolescent↗
PubMed1995

Selection of a highly enriched population of retrovirus-infected human hematopoietic progenitor cells using SNL fibroblasts.

Retrovirus-mediated gene transfer into human hematopoietic progenitor cells for therapeutic or experimental purposes has proved difficult due to low and variable infection efficiency. To address this, we have developed an in vitro system for the selection and maintenance of a highly-enriched population of retrovirus-infected hematopoietic progenitor cells. Human umbilical cord CD34+ cells were cultured on SNL, a neo-containing murine fibroblast cell line used for embryonic stem cell culture. SNL-supported CD34+ cultures could be maintained with continuing blast cell and CFU-GM production for eight weeks, compared to four weeks in the absence of SNL. We then tested the ability of SNL to facilitate the selection in G418 of CD34+ cord cells infected with the neo-containing retrovirus, vsn-2. While all cells in the control cultures died within 14 days, vsn-2-infected CD34+ cells continued to proliferate, differentiate and produce CFU-GM for up to five weeks after infection. 100% of individually-plucked CFU-GM from such cultures were shown by PCR to be successfully infected. This approach should be useful for experimental work and, since it would diminish competitive repopulation between infected and uninfected progenitors, may also be utilized, with modification, for optimizing gene therapy protocols.

3T3 Cells↗
PubMed1994

From RNA to sequenced clones within three days: a complete protocol.

Detection of specific mRNA transcripts by the reverse transcription/polymerase chain reaction (RT/PCR) technique has become increasingly important. The technique is fast and has a very high resolution. Cloning of these PCR fragments into vectors is sometimes necessary for identification of alternative splicing products, for bacterial expression or for generation of a DNA probe. Here we present a complete protocol for RT/PCR, cloning and sequencing of PCR, cloning and sequencing of PCR products beginning with the total RNA and ending with the DNA sequence within three days. To illustrate the procedure as an example, a fragment of the human glyceraldehyde-3-phosphate dehydrogenase mRNA was amplified from total RNA, cloned and partially sequenced. The protocol has been optimized for small scale to facilitate handling and to reduce costs.

Base Sequence↗
PubMed1995

Adrenocortical carcinoma: epidemiology and natural history.

Information about epidemiology, natural history and prognostic factors of adrenocortical carcinoma in Italy is extremely scarce. We report here 35 patients of adult age who were referred to our institution in the last two decades. Nine patients had non functioning, and 26 had functioning tumors. In non-functional tumors initial symptoms were abdominal pain in 90% of cases, fever, weakness, malaise, weight loss in 30%. Only one patient was asymptomatic. Of patients with functioning tumors, 18 presented with Cushing's syndrome, 6 with Cushing's syndrome and virilization, 1 with Cushing's syndrome and feminilization and 1 with hyperaldosteronism. Twenty-two of all cases (63%) had metastases at diagnosis; most frequent sites were lung, liver and distant lymph nodes. The results of tumor staging, according to MacFarlane system, were: stage I, 1 patient (3%); stage II, 10 patients (28%); stage III-IV, 24 patients (69%). Twenty-six out of 35 patients underwent removal of the mass with complete adrenalectomy. Twelve patients received mitotane alone; 8 mitotane and chemotherapy; 5 chemotherapy alone; 2 radiotherapy associated with mitotane or chemotherapy; 1 anthalgic radiotherapy. Survival time ranged from 1 to 108 months. One-year survival rate was 60%, and 5-year survival rate was 10%. Lower survival rate compared with that reported from other countries is probably related to the referring of patients at very advanced stages of disease. Early recognition and referral, in addition to optimization of therapeutic protocols by multicenter studies, may improve prognostic aspects.

Actuarial Analysis↗
PubMed1995

Therapeutic range in transscleral contact cyclophotocoagulation.

Laser contact cyclophotocoagulation (CP) increasingly replaces noncontact CP and cryotherapy as it produces less damage to the conjunctiva and sclera. However, the optimal wavelength and protocol for treatment have not yet been firmly established. We used a contact continuous-wave (cw)-Nd:YAG laser at 1064 nm (Meridian-Microruptor III) with a bare fiber. A total of 30 freshly enucleated porcine eyes with brown irides were treated within 12 h of enucleation. The intraocular pressure was kept at 35-40 mmHg with an infusion system. The fiber was placed at a 1.5-mm distance from the limbus perpendicularly to the scleral surface, and applications were made using power levels ranging from 1.0 to 10.0 W for exposure periods of 0.5, 0.7, 1.0, 1.5, 2.0, 3.0, and 4.0 s. A just-visible whitening of the ciliary body was defined as a minimal effect, a complete whitening without loss of ciliary structures was defined as a medium effect, and a complete whitening with loss of ciliary structures was defined as a maximal effect. Supramaximal "pop" effects could be identified by the typical sound and the destruction of the ciliary body. Pop effects originate from a sudden overheating, which leads to the formation of small gas bubbles. Using an exposure duration of 0.5 s, no pop effect or maximal effect was observed. For longer exposure periods the therapeutic range decreased continuously (3.7 +/- 2.7 W for 0.5 s, 0.3 +/- 0.3 W for 4.0 s).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗