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Biomedical subjects

L M Kernoff

Publications and source records attributed to L M Kernoff.

17 recordsLinked to original sources

Platelet collection using the IBM 2997 cell separator.

Platelets were collected using the dual-channel module on the IBM 2997 Blood Fraction Separator. We carried out 320 procedures to harvest platelets for therapeutic purposes and yielded 5.1 +/- 1.5 X 10(11) platelets (mean +/- SD). Infusion into previously unsensitized recipients with hypomegakaryocytic thrombocytopenia achieved increments at 1 hr of 19 +/- 7.3 X 10(9)/liter/m2 (mean +/- SD) and at 24 hr of 15 +/- 6.3 X 10(9)/liter/m2. The only consistent donor reaction was mild hypocalcaemia, easily corrected by calcium gluconate infusion. Changes in donor packed-cell volume and white cell count were not statistically altered (p greater than 0.05) but donor platelet counts fell from 216 +/- 43.1 X 10(9)/liter to 162.5 +2- 41.7 X 10(9)/liter (mean +/- SD) (p less than 0.01). Additional plateletphereses were carried out in seven normal volunteers, using the same technique, in order that the function of the harvested platelets could be studied. Following radiochromium labelling and reinfusion into the same donors, normal in vivo recoveries were obtained at 10 min (59.4 +/- 3.4%; mean +/- SD) and platelet mean life span was also normal (218 +/- 12 hr; mean +/- SD). Furthermore, in vitro platelet factor III availability and aggregation patterns of the harvested platelets did not differ from control values and their ultrastructural appearance was normal.

Blood Platelets↗

Hypocomplementaemia fails to prevent acute-phase stimulation of fibrinogen synthesis.

Fibrinogen synthesis rates of normocomplementaemic and hypocomplementaemic rats were measured after turpentine injection using the 14C-carbonate technique and a liver perfusion system. In both groups of animals turpentine administration caused a significant increase (P less than 0,01) in fibrinogen synthesis rates, but no significant difference was observed between the two groups. These results suggest that complement does not play an important role in the genesis of the fibrinogen acute-phase reaction.

Animals↗

Complement (C3) binding to platelets in autoimmune thrombocytopenia.

In view of conflicting reports on the occurrence of complement binding to platelets in idiopathic autoimmune thrombocytopenic purpura (AITP) we performed measurements of platelet bound C3 in patients with AITP who had elevated levels of platelet bound IgG. Using a quantitative antiglobulin consumption technique 38 out of 42 patients were found to have fixed abnormally large amounts of C3 to their platelets, and a significant positive correlation between the amounts of platelet bound IgG and C3 was shown to exist. In additional experiments antibody eluates were prepared from AITP platelets and were shown to cause the fixation of C3 to normal donor platelets in vitro. Taken together these findings strongly suggest that the C3 binding in AITP is specifically related to the disease process.

Autoantibodies↗

Congenital factor VII deficiency. Clinical and laboratory characteristics of a newly discovered kindred.

Four generations of a newly discovered kindred suffering from congenital factor VII deficiency have been studied. The abnormality was transmitted as an autosomal recessive character and resulted in homozygotes with less than 1% factor VII procoagulant activity. Antibody neutralization tests using a monospecific rabbit anti-human factor VII antibody demonstrated the presence of factor VII antigen in excess of factor VII procoagulant activity. The disorder has therefore resulted from the presence of a functionally abnormal factor VII molecule and not from a true deficiency of this factor. When the plasmas from the homozygotes were tested in the prothrombin time test using human, rabbit and ox tissue thromboplastins, a progressive diminution in the ability of these reagents to detect the factor VII procoagulant deficiency was observed. These differences were however small and the complete insensitivity of ox brain thromboplastins that characterizes the factor VII Padua abnormality was not observed.

Adolescent↗

Autopsy findings in an elderly man suffering from severe von Willebrand's disease.

A platelet derived growth factor released following platelet adhesion to the subendothelium of damaged arteries may promote the development of atherosclerotic lesions. Consequently patients with von Willebrand's disease in whom platelet adhesion is abnormal may be protected from atherosclerosis. This possibility was investigated by performing an autopsy study on an elderly patient who had suffered from severe von Willebrand's disease. Extensive atherosclerotic lesions were found at post mortem suggesting that platelets may not play a clinically significant role in the causation of atherosclerosis.

Aged↗

The role of continuous-flow blood fraction separators in clinical practice.

Continuous-flow blood fraction separators facilitate the efficient exchange of large volumes of plasma or red cells and therefore have clinical application in the rapid correction of abnormalities located predominantly in either of these compartments. Plasmapheresis has been successfully used in managing 2 patients with previously refractory myasthenia gravis, in reducing the antibody titre in a rhesus-sensitized woman, and in diminishing anti-A titre in a patient requiring bone marrow transplantation from an ABO-incompatible but HLA- and MLC-identical sibling. Continuous-flow red cell exchange effectively reduced the haemoglobin S concentration in an individual with sickle cell disease prior to general anaesthesia and abdominal surgery. Complications were not encountered although the procedures were carried out repetitively over prolonged periods of time. All 5 patients tolerated their exchanges without discomfort. As with any new and expensive technique, caution should attend the introduction of continuous-flow plasma or red cell exchange into clinical medicine. Careful evaluation of the safety and the benefits is needed to establish perspective and to distinguish between established and developmental indications.

Acetylcholine↗

Platelet-bound IgG measurements in idiopathic thrombocytopenic purpura.

A quantitative antiglobulin consumption technique has been used to measure antiplatelet antibody (platelet-bound IgG) in 25 patients with idiopathic thrombocytopenic purpura (ITP). The assay confirmed the presumptive clinical diagnosis in all patients. Additional observations however, have demonstrated that if thrombocytopenic patients have platelet counts greater than 75 x 10(9)l, false-negative results may be obtained. Antiplatelet antibody levels closely mirrored the clinical progress of patients receiving therapy, but the level of antibody at the time of diagnosis was not of value in predicting the response to corticosteroid treatment. In a proportion of patients receiving corticosteroids, platelet counts returned to normal before antibody levels, implying a reduction in the sequestration of antibody-sensitized platelets within the reticulo-endothelial system. Because this response was observed in proportionately more patients in whom drug therapy was successful than others, this steroid effect may in some patients be an important factor in determining the successful outcome of medical treatment. Four out of 10 patients in clinical remission had evidence of disease activity based on platelet antibody and platelet survival measurements. The pattern of results obtained demonstrates that disease activity may go unrecognized in some patients unless both measurements are performed.

Adolescent↗

The University of Cape Town leukaemia centre: the first 5 years.

In the last 5 years there has been an increasing commitment to cell support regimens and bone marrow transplantation in leukaemia and the clinical service has developed in parallel with laboratory-based research programmes. In the acute leukaemias there has been a major attempt to improve diagnostic accuracy and to classify the tumours functionally, while the clinical approach is currently comparing bone marrow transplantation during the first complete remission with early or late cytotoxic intensification programmes. As regards cell support, allogeneic granulocytes and platelets are being provided for patients in both the leukaemia and the transplantation programmes. In addition, new techniques are being developed for increasing the efficiency of cell collection and characterizing their in vitro function. Bone marrow transplantation is the preferred form of treatment for patients with severe acute aplastic anaemia. Laboratory research is directed at defining graft-versus-host disease and attempting to eliminate this phenomenon with immunological adjuvants.

Academic Medical Centers↗

Demonstration of increased platelet-bound IgG in infectious mononucleosis complicated by severe thrombocytopenia.

In an attempt to confirm the immune nature of the thrombocytopenia complicating infectious mononucleosis, the amount of IgG bound to the platelets of 2 affected patients was measured. Using a sensitive quantitative antiglobulin consumption technique, increased amounts of IgG were demonstrated during the thrombocytopenic phase of the illness. This observation represents convincing evidence in favour of platelet destruction by an immune mechanism.

Adult↗

Influence of the amount of platelet-bound IgG on platelet survival and site of sequestration in autoimmune thrombocytopenia.

Seventeen patients with idiopathic autoimmune thrombocytopenic purpura were studied in order to establish whether the amount of platelet-bound antibody influenced the rate and site at which these platelets were destroyed. Platelet-bound antibody was measured by a quantitative antiglobulin consumption technique, and platelet survival and sites of sequestration were determined by the use of 51Cr-labeled platelets and surface radioactivity measurements. A correlation significant at the 5% level was observed between the amount of platelet-bound antibody and the rate of platelet destruction. A highly significant correlation (p less than 0.001) existed between antiplatelet antibody and spleen: liver surface radioactivity ratios, demonstrating that greater amounts of antibody bound to platelets result increasingly in their destruction within the liver.

Adult↗

Utilization of iron dextran in recurrent iron deficiency anaemia.

Previously published studies have documented a reduction in the rate at which iron stores laid down by iron dextran therapy can be utilized for haemoglobin synthesis after the acute demands of haemorrhage and phlebotomy. In order to determine if a defect in the mobilization of these stores exists in the face of a chronic stimulus to red cell production, 93 patients who had previously received a total dose infusion of iron dextran were examined for a recurrence of iron deficiency anaemia, and in those in whom anaemia had recurred, iron stores were assessed by marrow aspiration. Twenty of the 93 patients were found to have recurrent iron deficiency anaemia, and marrow aspiration in all failed to demonstrate stainable iron stores. Although the rate at which iron dextran can be mobilized from storage sites is reduced, the present study demonstrates that ultimately these stores are fully utilizable.

Anemia, Hypochromic↗

The effect of hypophysectomy and growth hormone replacement on albumin synthesis and catabolism in the rat.

Albumin synthesis and catabolism were respectively measured by McFarlane's (1963) sodium [(14)C]carbonate method and I-labelled albumin in hypophysectomized rats, both untreated and treated with growth hormone. Hypophysectomy resulted in a decrease in both albumin synthesis and catabolic rates. These changes as shown by pair-feeding experiments could not be ascribed to decreased food intake alone. Growth hormone was shown to partially restore both albumin synthesis and catabolic rates. It is proposed that growth hormone stimulates albumin synthesis and that its effect on albumin catabolism is secondary to changes in the mass of the intravascular albumin pool.

Animals↗

Exchange transfusion in sickle cell disease using a continuous-flow blood cell separator.

An exchange transfusion was performed preoperatively on a patient with sickle cell disease using a continuous-flow blood cell separator. An exchange of 2,825 ml red blood cells achieved a hemoglobin A level of 90.8 per cent. The continuous-flow blood cell separator appears to offer a safe and effective method of exchange transfusion in sickling disorders.

Adult↗