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Biomedical subjects

M S Horowitz

Publications and source records attributed to M S Horowitz.

At least 19 recordsLinked to original sources

SD Plasma in TTP and coagulation factor deficiencies for which no concentrates are available.

Clinical studies of SD-Plasma (SDP) have included treatment of patients with both the acute and chronic relapsing (CRTTP) forms of TTP and replacement of coagulation factors in patients with congenital deficiencies. With the infusion of SDP in 6 patients with CRTTP, platelet counts rose, LDH values dropped, hemoglobin levels remained constant, and the patients continued in good health. In an FFP-controlled study in acute TTP, 16 patients were exchanged with SDP and 10 with FFP. There was no difference between the two groups in patient survival; relapse or remission rate; incidence of treatment resistance; or in per patient total volume infused, number of treatments, average volume per treatment, or number of relapses. Finally, 48 coagulation factor-deficient patients received SDP for surgical prophylaxis, active bleeding and routine prophylaxis for Factor XIII deficiency. The expected levels of the deficient factors were achieved, and the treating physicians concluded that there was control of bleeding.

Blood-Borne Pathogens↗

Viral safety of solvent-detergent treated blood products.

Laboratory research commencing in 1982 led to licensing in the United States in 1985 of a solvent/detergent (SD)-treated anti-haemophilic factor (AHF) concentrate. Licensing was based on (a) studies demonstrating the inactivation of several marker viruses [vesicular stomatitis virus (VSV), Sindbis virus, Sendai virus], human immunodeficiency virus (HIV), hepatitis B virus (HBV), and non-A, non-B hepatitis virus [NANBHV; now known to be principally hepatitis C virus (HCV)] added to AHF just before treatment, (b) the realization that the principal viruses of concern in a transfusion setting (e.g. HIV, HBV, NANBHV) were all lipid-enveloped, and (c) laboratory, preclinical and clinical evidence indicating that AHF and other proteins present in the preparation were unaffected. The applicability of the SD method to a wide range of products and preparations, high process recoveries, and a growing body of viral safety information linked with the failure of several other virus inactivation methods to eliminate hepatitis transmission fostered the adoption of SD technology by more than 50 organizations world-wide. SD mixtures are now used in the preparation of products as diverse as intermediate purity and monoclonal antibody purified AHF and other coagulation factor concentrates, fibrin glue, normal and hyperimmune IgG and IgM preparations including those derived from tissue culture, plasma for transfusion, and various diagnostic controls. Over four million doses of SD-treated products have been administered, and numerous laboratory and clinical studies designed to assess virus safety have been conducted. SD treatment has been shown to inactivate > or = 10(9.2) tissue culture infectious doses (TCID50) of VSV, > or = 10(8.8) TCID50 of Sindbis virus, > or = 10(6.0) TCID50 of Sendai virus, > or = 10(7.3) duck infectious doses of duck HBV, > or = 10(11.0) degrees TCID50 of HIV-1, > or = 10(6.0) TCID50 of HIV-2, > or = 10(6.0) chimpanzee infectious doses (CID50) of HBV, > or = 10(5.0) CID50 of HCV, > or = 10(6.0) TCID50 of cytomegalovirus, > or = 10(5.8) TCID50 of herpes simplex virus type 1, > or = 10(4.0) TCID50 of PI-1, > or = 10(6.0) TCID50 of murine leukemia virus (Mov-3), > or = 10(4.0) TCID50 of murine xenotropic virus, and > or = 10(2.0) TCID50 of Rauscher murine leukemia ecotropic virus. Moreover, in ten prospective clinical studies, 0/53, 0/427, and 0/455 patients susceptible to HBV, NANBHV (HCV), and HIV became infected on follow-up.(ABSTRACT TRUNCATED AT 400 WORDS)

Biological Products↗

Successful resuscitation and neurologic recovery from refractory ventricular fibrillation after magnesium sulfate administration.

A 46-year-old man suffered a witnessed cardiac arrest. Ventricular fibrillation persisted despite 62 minutes of basic and advanced cardiac life support measures in the field. On arrival in the emergency department, he received 4 g magnesium sulfate IV and was defibrillated successfully to normal sinus rhythm with the next countershock. The patient was discharged neurologically intact. We discuss the possible mechanisms of action and clinical use of IV magnesium sulfate in cardiac arrest.

Cardiopulmonary Resuscitation↗

Improvement in plasma protein concentrations with fibronectin treatment in severe malnutrition.

Severely malnourished young children (n = 72) were treated with intravenous fibronectin to assess its efficacy as an adjunct treatment for kwashiorkor and/or marasmus. The protein was given in a double-blind study during the first 4 d of hospitalization together with standard nutrition and supportive therapy. Fibronectin concentrations as well as albumin, transferrin, prealbumin, and alpha-2-macroglobulin were monitored in samples taken before each dose of fibronectin and in samples taken five times thereafter. Sick individuals had significantly lower concentrations of all five proteins than did healthy control individuals of matching ages. Mean fibronectin concentrations were 98 +/- 7 mg/L (mean +/- SEM) for sick vs 303 +/- 21 mg/L for healthy individuals. Concentrations of all five proteins increased at a greater daily rate in patients treated with fibronectin than in patients who received placebos. Eighty-seven percent of the treated children survived to the end of the treatment and observation periods (mean hospitalization 14.7 d) whereas only 56% of the control subjects survived (P = 0.004). These data support the use of intravenous fibronectin as an adjunct in the treatment of severe malnutrition at a dosage of 7.5 mg.kg-1.d-1 over a 4-d period.

Blood Proteins↗

Virus safety of solvent/detergent-treated antihaemophilic factor concentrate.

The safety of an antihaemophilic factor concentrate treated with the organic solvent tri-(n-butyl)phosphate and sodium cholate (factor VIII-SD) was assessed for transmission of non-A, non-B (NANB) hepatitis and human immunodeficiency virus (HIV). Patients enrolled in the study had no previous exposure to blood products made from plasma pools, although 5 had received small quantities of single-donor products. All but 1 had normal alanine aminotransferase (ALT) levels, none had markers of HIV infection, and all had been vaccinated against hepatitis B. After treatment with factor VIII-SD, serum ALT levels and HIV antibody were monitored for up to 1 year. 20 patients received 625 to greater than 40,000 U (total 163,000 U, median dose 3900 U), and 17 of these were followed up for at least 6 months: transmission of either NANB hepatitis or HIV was not observed.

Adolescent↗

Clinical effects of alpha-interferon dose variation on laryngeal papillomas.

Achieving optimal clinical control of recurrent respiratory papillomatosis with prolonged treatment with human leukocyte (alpha) interferon appears to be dose-related and often requires individualized dosage elevation. Six of eight patients in this study needed a maximum dose of 18 x 10(6) IU/week for part of the therapy period to achieve better disease control. The strong correlation found between dosage and response suggests that it is the interferon causing the effect on disease expression, not just the unpredictable nature of the disease. An effect on papilloma growth was observed in all patients during IFN therapy. Three patients were able to be tapered off IFN with only minimal recurrence seen in one patient. No toxic side effects were observed.

Adult↗

The development of virus-free labile blood derivatives--a review.

Human blood plasma derived coagulation factor concentrates carry a substantial risk of virus transmission as traditionally prepared. Intensive investigations during the past 5 years have led to the development of several virus sterilization procedures which can be applied to these concentrates as well as to other labile protein derivatives. This review summarizes detailed information which is now available establishing the virucidal potency of these procedures, particularly with regard to the contaminating viruses of most concern: hepatitis B, non-A, non-B hepatitis and the AIDS virus. Currently utilized virus sterilization procedures have greatly reduced or eliminated the transmission of AIDS virus, HIV. The transmission of non-A, non-B hepatitis virus (NANBHV) has also been greatly reduced by some but not all of these procedures. Additional virus safety data in man will be required to establish whether any of the procedures gives products which are totally safe from NANBHV transmission and to assess their impact on other blood-borne viruses.

Animals↗

Intrathecal interferon in subacute sclerosing panencephalitis.

Five patients with clinically advanced subacute sclerosing panencephalitis (SSPE) were given human leukocyte interferon (IFN) by the lumbar route, 1 million IU every other day for a total of 30 days. Intrathecal IFN produced a meningeal inflammatory reaction in all patients and was associated with transient hemiparesis in 1. It persisted in the cerebrospinal fluid at measurable levels for 48 hours after a single injection. Although improvement was temporally related to intrathecal IFN in 1 patient, it is not clear whether this was induced by IFN or a spontaneous remission. A randomized controlled trial would be necessary to evaluate IFN critically as a therapy for SSPE.

Adolescent↗

Echocardiographic diagnosis of pericardial disease.

Echocardiograms were performed in 11 patients with constrictive pericarditis or effusive-constrictive pericarditis confirmed by cardiac catheterization and pericardiectomy. Three echocardiographic patterns of pericardial disease were noted and were related to three types of pericardial pathology. Parallel moving echoes separated by a clear space were reflected from chronically fibrosed and thickened pericardium without associated pericardial exudate. Effusive-constrictive pericarditis or subacute wet pericarditis was characterized on the echocardiogram by a posterior echo-free space representing the liquid pericardial effusion and multiple ultrasonic lines from the thickened visceral pericardium. Subacute dry pericarditis was associated with numerous ultrasonic signals filling the space between the visceral pericardium and the relatively flat parietal pericardium. These ultrasonic signals were reflected from coagulated pericardial exudate which was adherent both to the parietal pericardium and the visceral pericardium. Parallel moving echoes or dense bands of echoes were reflected from either or both thickened visceral and parietal pericardium.

Chronic Disease↗

Vegetative bacterial endocarditis on the prolapsing mitral valve. Echocardiographic evaluation.

Vegetative endocarditis on the prolapsing mitral valve can be diagnosed with an echocardiogram and the response to therapy can be followed with this technique. A dense mass of fuzzy echoes was noted on the prolapsing posterior leaflet of an echocardiogram from a patient with endocarditis. Three months after the initiation of antibiotic therapy, the mass of echoes had disappeared and was replaced by a dense linear echo, suggesting fibrosis of the part of the mitral valve that had been infected previously. Persistence of the echocardiographic evidence of endocarditis, despite negative blood cultures, may indicate persistence of the risk of peripheral embolization.

Echocardiography↗

Separation of two hepatitis B human antibody fractions by cold-ethanol precipitation.

Antibodies to three different samples of hepatitis B antigen-positive serum were found to be absent from a Cohn fraction II hepatitis B immune globulin preparation, but present in the whole plasma from which the immune globulin was made. Fractions containing the antibodies specific for the three antigen samples were isolated from the plasma by euglobulin precipitation, and the antibodies were characterized as to immunoglobulin class and precipitability in the Cohn fractionation procedure. They appear to be IgG antibodies which, however, were detectable only in Cohn fraction I, while the remainder of the HB specificity present in the original plasma was found, as expected, in fraction II.

Antibodies↗

Echocardiographic evaluation of the stent mounted aortic bioprosthetic valve in the mitral position. In vitro and in vivo studies.

Echocardiograms were performed on 20 clinically stable patients following mitral valve replacement with glutaraldehyde-preserved porcine aortic heterografts and three patients with antibiotic sterilized aortic homografts mounted in the mitral position. Such valves were evaluated in a test chamber at varied flow rates resulting in improved understanding of movements seen with the echocardiogram in vivo. The technique for recording the valvular stent and leaflets is described and a method for measuring several parameters is demonstrated. Initial diastolic slope averaged 2.4 +/- 0.5 cm/sec (range 1.9 to 3.3 cm/sec). Left ventricular outflow tract measured from the anterior portion of the stent to the interventricular septum averaged 1.5 +/- 0.5 cm at end-diastole and 1.3 +/- 0.6 cm at end-systole. Leaflet excursion averaged 1.5 +/- 0.3 cm (with a range from 1.0 to 2.1 cm). The ratio of internal to external stent diameters averaged 0.66 +/- 0.05 (with a range from 0.56 to 0.74).

Animals↗

Noninvasive diagnosis of complications of the mitral bioprosthesis.

The echophonocardiographic diagnoses of valvular and paravalvular insufficiency, calcific stenosis, and thrombolic occlusion of the stent-mounted aortic homograft or heterograft in the mitral position are described. Paravalvular and valvular insufficiency were associated with apical systolic murmurs which decreased in intensity after amyl nitrite inhalation and with echocardiograms which showed initial diastolic slopes of the stents in excess of the normal range (1.9 to 3.3 cm. per second). In clinically improved and stable patients, amyl nitrite inhalation resulted in increased intensity of the commonly heard systolic ejection type murmur at the left sternal border and echocardiographic evidence of further narrowing of the outflow tract measured between the interventricular septum and the anterior portion of the stent. Calcific homograpft stenosis was associated with a decreased diastolic stent slope (0.4 cm. per second) and increased echo density from the tissue leaflets. Thrombus formation on the sewing ring caused fatal inflow occlusion in 2 patients. The condition was characterized by an echocardiogram showing decreased ratio of internal-to-external stent diameter, 0.47 (normal range 0.56 to 0.74), decreased diastolic stent slope, and decreased leaflet excursion.

Adult↗