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Biomedical subjects

L Hoffer

Publications and source records attributed to L Hoffer.

10 recordsLinked to original sources
PubMed2000

Manufacturing of a prothrombin complex concentrate aiming at low thrombogenicity.

The paper describes the production of a prothrombin complex concentrate (PCC) with high virus safety and a well-balanced content of vitamin K-dependent clotting factors and inhibitors. Solid-phase extraction is followed in a second step by optimized anion exchange chromatography using a radial column. A step for virus removal by nanofiltration is introduced in addition to the solvent/detergent step. By speeding up the chromatographic step, the period of time required for production is reduced considerably. The activities of the four vitamin K-dependent clotting factors II, VII, IX and X are in ratios of about 1:1:1:1. Protein C, Protein S, and Protein Z are also present in therapeutically effective concentrations. The product shows no thrombogenicity, in either in vivo nor in vitro models. Clinical investigations show that the PCC is a safe and efficient preparation for the substitutive treatment of FIX or FVII in patients suffering from the respective deficiencies. All bleeding episodes have been efficiently controlled with relatively low doses of the concentrate. The surgical procedures have been conducted without any problems in severely FIX and FVIII deficient patients.

Animals↗
PubMed1999

Production of highly purified clotting factor IX by a combination of different chromatographic methods.

A highly enriched preparation of human clotting factor IX was produced by a combination of adsorption chromatography, hydrophobic interaction chromatography and heparin affinity chromatography. The introduction of adsorption chromatography with a hydroxyaminopropyl support allows the capture step to be carried out directly from the cryoprecipitate-depleted plasma with a chromatographic column in flow-through mode. This replaces the batch procedure used until now. The other two chromatographic steps are designed in such a way that the eluate from the preceding step can be directly applied, without any intermediate treatment of the sample. This cuts the period of time required for the process by almost 50%, and increases the yield considerably. The isolated factor IX contains practically no contaminants and has a specific activity over 200 IU/mg of protein.

Adsorption↗
PubMed1999

Active heroin injectors' perceptions and use of methadone maintenance treatment: cynical performance or self-prescribed risk reduction?

In addition to the numerous heroin users who voluntarily enter methadone treatment as a way to free themselves from illicit drug addiction and those ordered to do so by the courts, there are a large number of opioid users who enter methadone treatment with other objectives in mind. These include shorter-term goals that users do not necessarily equate with complete heroin abstinence. In this paper we report the results of a qualitative study designed to identify and describe the motivations active heroin users have for entering methadone treatment, and to suggest that many of these short-term methadone episodes may operate as self-prescribed attempts at risk reduction, and act as pilot tests for users considering or anticipating entering treatment to quit the use of illicit drugs. We argue that heroin users' motivations, perceptions about methadone, and the strategies they devise for adapting methadone treatment for their own needs should be recognized for their value in reducing the multiple risks associated with drug use.

Colorado↗
PubMed1997

Issues in the development of medical products based on human plasma.

Product development and process validation are shown in the case of several products obtained from human plasma. These are virus-inactivated plasma, intravenous immunoglobulins and the clotting factors VIII and IX. Different analytical methods are presented, which are used for product control and in-process control. For the production of virus-inactivated human plasma a down-scale protocol is presented, allowing a simulation of the production on a laboratory scale. Virus validation has shown that the reduction of transfusion-relevant viruses in the process was higher than six log steps. Determination of leachables from the RP-column, which was used in this production, proved that they appear in the final product in quantities below the detection limits only. It was also shown that the chemicals used for virus inactivation could be quantitatively removed from the product. For the isolation of other products, here intravenous gamma globulins and the clotting factors VIII and IX, similar validation steps had to be taken. In the case of clotting factor VIII the following data were determined, the reduction of viruses, the amount of leachables from the column, the residues of chemicals from the solvent/detergent treatment for virus inactivation. Virus reduction was successfully performed as well as the removal of chemicals used for virus inactivation. The amount of leachables from the columns used for chromatographic purification was found to be far below the permissible levels.

Biological Products↗
PubMed1995

Improved virus safety and purity of a chromatographically produced factor IX concentrate by nanofiltration.

A virus removal system based on tangential flow filtration was introduced into a Factor IX production process. Beside the intended virus reduction potency of filter membranes, an additional purification effect could be achieved. This purification effect was evaluated in detail by means of sodium dodecyl sulphate-polyacrylamide gel electrophoresis and size-exclusion HPLC. High-molecular-mass impurities were retained by the membrane, thus increasing the specific activity of the product.

Blood-Borne Pathogens↗
PubMed1994

Yohimbine impairs P50 auditory sensory gating in normal subjects.

The evoked response to repeated auditory stimuli generally decreases in amplitude, a phenomenon that demonstrates the activity of sensory gating mechanisms in the central nervous system (CNS). Gating of the P50 wave of the auditory evoked response shows such behavior in normals, but not in schizophrenic or manic subjects. In mania, diminished gating of the auditory evoked response is correlated with elevated levels of noradrenergic metabolites. In animals, yohimbine, a presynaptic alpha-2 antagonist, increases noradrenergic neuronal transmission in the CNS and diminished gating of the auditory evoked response. The aim of this experiment was to test whether yohimbine causes diminished auditory sensory gating in normal human controls. Seven normal subjects with normal P50 auditory gating were treated either with 0.4 mg/kg of oral yohimbine on one day or placebo on a different day. Each subject acted as his own control. Yohimbine, but not placebo, caused a significant but transient decrease in P50 auditory gating in these subjects. Thus, increasing CNS noradrenergic neuronal transmission in normal controls can cause a transient impairment in auditory sensory gating.

Acoustic Stimulation↗
PubMed1986

The pharmacokinetics of alfentanil in gynecologic surgical patients.

The pharmacokinetics and serum protein binding of alfentanil during continuous intravenous infusion were determined in 11 women who were either healthy (American Society of Anesthesiologists [ASA] physical status 1) or had mild systemic disease (ASA physical status 2). Anesthesia was induced with intravenous thiopental 2 mg/kg and alfentanil 50 micrograms/kg and maintained with constant intravenous alfentanil infusions of 1-3 micrograms/kg/min until approximately ten minutes before the end of surgery. Venous blood samples were obtained after the bolus of alfentanil was administered and at various times during and after the alfentanil infusion. Serum alfentanil concentrations were measured by gas-liquid chromatography. There was considerable interpatient variability in alfentanil pharmacokinetics and serum protein binding. The mean +/- SD alfentanil serum clearance, volume of distribution at steady state (Vss), and elimination half-life were 5.2 +/- 2.0 mL/min/kg, 0.47 +/- 0.1 L/kg, and 97 +/- 52 minutes, respectively. The mean fraction of alfentanil unbound in serum (fu) was 0.18 +/- 0.08. There was a time-dependent decrease in alfentanil serum clearance that correlated with increasing duration of surgery. This decrease in clearance resulted in a prolonged alfentanil half-life. These results indicate there is considerable interpatient variability in the pharmacokinetic parameters and serum protein binding of alfentanil in these patients and suggest that the infusion rate of alfentanil during maintenance anesthesia should be adjusted for individual patient response. Infusion rates may need to be tapered during prolonged operations.

Adult↗