Multiple Clinical Indications Research Articles

Clinical indications for use of fresh frozen plasma in dogs: 74 dogs (October through December 1999).

To document reasons for use of fresh frozen plasma (FFP) in dogs and determine variables that apparently triggered the decision to use FFP. Retrospective study. 74 dogs. Medical records of dogs that received FFP at a veterinary teaching hospital during a 3-month period were reviewed. The 74 dogs underwent 144 transfusion episodes (TE; a TE was defined as 1 day of transfusion therapy) and received 252 units (120 ml/unit) of FFP. Fresh frozen plasma was administered to provide coagulation factors (67 TE), albumin (91), alpha-macroglobulin (15), or immunoglobulins (19); for some TE, multiple clinical indications were identified. Variables that apparently triggered the decision to administer FFP included active hemorrhage with or without prolongation of coagulation times, low total plasma protein concentration, persistent vomiting associated with pancreatitis, and sepsis. Mean doses of FFP for each indication were between 8.5 and 9.4 ml/kg (3.9 and 4.3 ml/lb). Small dogs were generally given higher doses (mean dose, 13.9 ml/kg [6.3 ml/lb]) than large dogs (mean dose, 5.1 ml/kg [2.3 ml/lb]). Fifty (68%) dogs were alive at the time of discharge from the hospital. Results suggest that FFP plays an important role in the care of critically ill dogs. Because the supply of FFP is limited, guidelines for when administration of FFP may be clinically useful should be developed.

Bonnes pratiques cliniques de la nébulisation

A meeting on nebulization held in April 1997 defined good clinical practices. Guidelines that were proposed pertained to the following: pneumatic and ultrasonic nebulizers; delivering circuit, occluded or not, the choice of the tip being done according to the disease to treat and to the drugs to be delivered; various functions, depending on the type of nebulizer; the particle size, as it will indicate which disease may be treated: between 2 and 6 μm for bronchi, between 0,5 et 3 μm for lung, > 5 μm for ear, nose and throat diseases; compatibility between the type of nebulizer and drugs. Ten drugs are currently registered in France. Nebulization has multiple clinical indications, such as asthma, cystic fibrosis, chronic obstructive pulmonary disease, Pneumocystis carinii pneumonia, acute laryngitis, and in infants, acute bronchiolitis. The prescription must be detailed, and the physician should make sure that the medical staff put it into application.

New Advances in Interferon Therapy of Cancer

Substantial increases in both the understanding of the cellular mechanisms of actions of interferon (IFN) and in its clinical use in cancer have occurred in recent years. The efficacy of interferon for the treatment of select malignancies has been established, and IFN-&agr; and IFN-&bgr; have been approved by the Food and Drug Administration for multiple clinical indications. IFN-&agr; increased median survival and relapse-free survival in patients with locally advanced melanoma when used as adjuvant therapy and had modest activity against advanced disease. In other tumors where studies indicated that IFN lacked direct therapeutic activity, clinical trials suggested that it increased the antitumor activity of cytotoxic chemotherapeutic agents when used in combination therapy. IFN has substantial activity in chronic myelogenous leukemia, increasing survival in patients in early chronic phase when compared with conventional chemotherapy, and has some activity in non-Hodgkin's lymphoma in combination with cytotoxic agents. Recent molecular and pharmacologic studies defining cellular receptor activation, signal transduction pathways, and biochemical modulating activities of interferon have yet to be fully incorporated into clinical development. Further preclinical advances along with the expanding identification of potentially clinically sensitive tumors make it likely that the use of IFN in cancer chemotherapy will continue to grow.

The median paralysis unit: A more pharmacologically relevant unit of biologic activity for botulinum toxin

Although the ld 50 has been used to quantify the biologically active toxin in clinical preparations of botulinum A toxin (Botox ® and Dysport ®), a discrepancy exists between the clinical potency of equivalent international units of different formulations of botulinum A toxin for multiple clinical indications. Our laboratory previously reported that a regional chemodenervation assay in the mouse could be utilized to detect the difference in the potencies of the clinical preparations of toxin [Pearce et al. (1994) Toxic. appl. Pharmac. 128, 69–77]. The purpose of this study was to quantify the regional paralysis produced by botulinum toxin and define a new pharmacologic/biologic unit of activity that more accurately reflects the mechanism of action of botulinum toxin in the clinical setting. Quantal analysis of regional paralysis revealed that the ed 50, defined as the median paralysis unit (MPU) for Botox ® and Dysport ®, was 0.41 ± 0.01 and 1.00 ± 0.02 ld 50 units, respectively. Differences in the potencies found in retrospective clinical studies comparing Botox ® and Dysport ® were accurately reflected, for the first time, by the dose of toxin expressed in terms of the MPU (median paralysis unit). The data suggested that the MPU may be a more appropriate measure of the biologic activity in therapeutic formulations of botulinum toxin.

Diaspirin crosslinked hemoglobin (DCLHb) does not affect the anesthetic potency of isoflurane in rats.

Hemoglobin solutions are being developed as oxygen carrying fluids for multiple clinical indications. Despite an early report of accentuation of ether anesthesia, the effect of hemoglobin on anesthetic potency has not been assessed. We assessed the effect of alpha-alpha diaspirin crosslinked hemoglobin (DCLHb) on the anesthetic requirement of isoflurane necessary to keep rats unresponsive to noxious stimuli (1.0 MAC [minimum alveolar concentration]). During isoflurane administration, each rat received one of the following fluid regimens: 44Hct/N-normal hematocrit and volume; 44Hct/H-8.0 ml of donor blood given as a hypervolemic bolus; 30Hct/H-5.0 ml of DCLHb given as an exchange transfusion and 8.0 ml as a hypervolemic bolus; or 16Hct/H-15.0 ml of DCLHb given as an exchange transfusion and 8.0 ml as a hypervolemic bolus. MAC was determined using a standard tail clamp technique. The isoflurane requirement to achieve 1.0 MAC was not different between the four groups. These results are consistent with a hypothesis that DCLHb does not change the anesthetic state.