Biomedical subjects
P Jacobs
Publications and source records attributed to P Jacobs.
von Willebrand's disease in Zimbabwe. A report on 3 families.
Three families with clinically typical features of von Willebrand's disease are described. One family had features to suggest type II disease. Von Willebrand's disease appears to be rare in Africa, but this may be due both to lack of awareness among clinicians and insufficient laboratory facilities.
Thyroid lymphoma and its management.
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Disseminated intravascular coagulation--is there a place for plasma exchange.
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The Dracula factor--red cell loss due to repeated blood sampling.
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Examination of the bone marrow in severely septic patients with neutropenia.
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Thrombotic thrombocytic purpura--plasma infusion or exchange?
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Treatment of aplastic anaemia with antilymphocyte globulin and high-dose methylprednisolone.
Twenty-three consecutive adults with bone marrow aplasia who, apart from one individual, lacked a sibling suitable for allogeneic transplantation, received five daily infusions of 50 mg/kg of antilymphocyte globulin (ALG) concurrently with high-dose (500 mg) methylprednisolone (HDMP), followed by oral prednisone at a dose of 30 mg until day 30. One patient died early so that response could not be determined, but data are available and included in the toxicity as well as survival analysis. Haematological response occurred in 13 of the remaining 22 (59%). This followed a single course of treatment in 12, with complete response achieved in five of this group and a second course required in one. At a median follow-up of 20 months (range 5-60), there have been five relapses and 13 patients are alive, including 12 responders who have Karnofsky ratings between 90% and 100%. Of the other nine individuals, only two are alive, with 1 at 12 months still requiring active support and the second, after failing further courses of treatment, at 41 months having a partial response to lymphocytapheresis and plasma exchange. Failure to respond was a significant adverse predictor for survival (P = 0.022). This study involved two distinct batches of ALG, with response occurring in 1/7 (14%) patients treated with the first lot, but in 12/15 (80%) of those individuals who were treated with the second (P = 0.007). Only a pretreatment mean cell volume (MCV) greater than 100 fL predicted for response (P = 0.0088). Confirmation is hereby provided for the efficacy of ALG used in combination with HDMP for treatment of aplastic anaemia, with further support for the observation that not all batches of this product are comparable in bringing about haematologic response in these individuals.
Refractory ascites in the chronic myeloproliferative syndrome: a case report.
In a patient with myelofibrosis, tense ascites refractory to conventional therapy resulted from extensive seeding of the peritoneum with colonies of extramedullary haematopoiesis. Whole abdominal radiation was found to be effective and well tolerated, and brought about prompt and lasting resorption of the exudate, with weight reduction and improvement in performance status from 50% to 90% on the Karnofsky rating.
Reactivity of pretransplant cytotoxic antibodies to a selected HLA panel is not influenced by cyclosporin A, with or without plasma exchange.
The influence of 6 weeks of cyclosporin A (CYA), followed by a further 6 weeks of this agent in combination with plasma exchange (PE), was defined on panel reactivity and titre of preformed cytotoxic antibodies in stable patients on haemodialysis awaiting renal transplantation. Nine individuals with antibodies to 30% or more of the donor panel were entered into the study, but three failed to complete the programme. Comprehensive data are available on the remaining six patients, one of whom was studied twice. The pattern of reactivity to the panel was unaltered, but antibody titres were significantly reduced (P less than 0.006). In one patient, a lymphocytoxic crossmatch performed between the patient and an HLA-haploidentical sibling in the last week of the trial was positive, suggesting that neither procedure was successful in removing an antibody directed against the HLA antigens of a family donor. Three cadaver renal transplants were performed during or after the trial, and while two of the grafts were unsuccessful, one survives at 60 months, with good function. From these data it is concluded that neither cyclosporin A nor its combination with plasma exchange have any effect on the panel reactivity of preformed cytotoxic antibodies, whereas the titres were significantly reduced. An important and serious side effect of the apheresis procedure was the loss of fistulae in two patients.
Collection and cryopreservation of human stem and progenitor cells for bone marrow transplantation.
Bone marrow collection was undertaken from human organ donors (Group 1: n = 7) to develop a closed-system single-step technique for stem and progenitor cell enrichment, using the Cobe 2997 continuous-flow blood-cell separator. The effects of programmed freezing, storage in liquid nitrogen, and thawing were then defined using these grafts. Once standardised, this method was extended to autografting following cryopreservation of a comparable fraction (Group 2: n = 8) and then to allogeneic transplantation after ex vivo exposure to the lytic monoclonal antibody. Campath-1 IgM and human complement, but without cryopreservation (Group 3; n = 9). The median number of mononuclear cells harvested was 5.0 x 10(6)/mL (n = 24), and this was not significantly different in the three groups. The ex vivo graft, composing marrow rich anticoagulated whole blood, was recirculated in the separator at a flow rate of 60 mL/minute, with a centrifuge speed of 1,100 r.p.m., and the mononuclear cell fractions were collected at the rate of 1.5 mL/minute. The average procedure time from formation of the interface in the single disposable channel to achievement of the final volume was 90 minutes. The mean recovery of the mononuclear cells was 101.4% (SD 38.0) and the GM:CFUc was 91% (SD 43.86). These figures were not significantly influenced by subsequent cryopreservation (Group 1; n = 7 and Group 2; n = 8) or following exposure to the monoclonal antibody. Campath-1 IgM (Group 3; n = 9).(ABSTRACT TRUNCATED AT 250 WORDS)
In vitro study of immunologic changes in long-term cytapheresis donors.
Several in vitro measurements of immune function were examined retrospectively in a population of active long-term cytapheresis donors (group I; n = 50) and the results were compared to age- and sex-matched controls (group II; n = 50) who had donated only whole blood. In group I, significantly different mean absolute lymphocyte counts (P = .0025), total T-cells (P = .0026) and T-helper cells (P less than .0001), and helper-to-suppressor ratios (P = .0279) were present. No differences were noted between the two groups for peripheral blood mean B-cell count, T-suppressor numbers, lymphocyte responsiveness to mitogens or alloantigen, and serum immunoglobulin level. The reduced mean absolute lymphocyte count in group I was due to the reduction in T-helper cell numbers and accounted for the imbalance in the helper-to-suppressor ratio. These disturbances are currently unexplained and, while no clinical consequences have so far become evident, there is a need to continuously monitor the immunologic status of cytapheresis donors. It is also important to determine whether reversal of the defects occurs and, if so, over what time interval.
The efficacy of maternal age screening for Down's syndrome in Wessex.
The uptake of amniocentesis in Wessex for the period 1986-1988 was 36 per cent (2873 of 8004 births), a proportion that has not altered significantly since 1984. There is a large difference in uptake between women in the lower risk age group, 35-36 years, and those in the higher risk group, 37+ years, and very considerable differences in uptake among different districts. The prenatal detection over the 3-year study period for women aged 35 or more, after correction for spontaneous loss of Down's syndrome fetuses between prenatal detection and birth, is 53 per cent, a figure that must be inflated due to our failure to ascertain all liveborn Down's syndrome patients.
Plasmodium falciparum: recombinant baculoviruses direct the expression of circumsporozoite proteins in Spodoptera frugiperda cell cultures.
The DNA coding for the circumsporozoite protein (CPS) of Plasmodium falciparum has been cloned into the baculovirus expression vector pAcYM1 and expressed in Spodoptera frugiperda (Sf9) insect cells. Three DNA constructs have been made: the first one directs the synthesis of the complete CSP (aa 1-412), the second leads to the production of a species devoid of the anchor domain (aa 1-391) and the third one to a molecule lacking both signal and membrane anchor sequences (aa 18-391). All three recombinant CPS were produced at about 3 micrograms per 10(6) infected cells and were characterized in terms of immunoreactivity and apparent molecular weight. Analytical purification of the recombinant proteins was achieved by a combination of heat treatment, acidification, isoelectric focusing and ion exchange chromatography. The purified material, when injected into mice, generated only modest antibody responses, although antisera from immunized mice reacted with control CSP antigens carrying or not the major immunodominant repeat region.
Athletes' pseudoanaemia.
To characterize the so-called pseudoanaemia of endurance-trained athletes, the plasma volume (PV), red cell volume (RCV) and total blood volume (TBV) of 12 male and 12 female athletes and 5 male and 5 female nonexercising controls were measured using 125I-labelled human serum albumin and 51Cr-labelled erythrocytes. The mean PV of the male athletes (52.8 ml.kg-1) was 37.5% higher than that of the controls (38.4 ml.kg-1), while the 18.1% increase measured in the female runners (51.5 ml.kg-1) over the controls (43.6 ml.kg-1) was a novel observation. Although the RCV was significantly greater (34.7%) in male athletes (32.6 ml.kg-1 vs 24.2 ml.kg-1 in the controls), a similar elevation (3.6%) was not found in the female athletes (25.9 ml.kg-1) compared to the sedentary women (22.8 ml.kg-1). This could have been due to iron-limited erythropoiesis because the RCV of the female athletes defined as clinically anaemic was markedly lower that of the nonanaemic women (P less than 0.05). The elevated plasma protein mass and concentration measured in the athletes partly accounted for their expanded PV. It was concluded that the decreased blood haemoglobin levels reported in the endurance athletes was largely a dilutional effect.
Methotrexate encephalopathy.
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Different forms of chronic childhood thrombocytopenic purpura defined by antiplatelet autoantibodies.
To determine whether detection of antiplatelet autoantibodies (AAb) to glycoproteins IIb/IIIa and Ib/IX may be useful in defining different forms of chronic thrombocytopenic purpura (TP) in children, we analyzed for AAb the platelet and plasma samples from 36 children with chronic TP (mean duration 4.4 years), from 31 children with normal platelet counts at the time of blood sampling but with chronic TP in the past (mean duration 2.9 years), and from 23 adults with chronic TP; the results were correlated with the clinical data. Antiplatelet autoantibodies were detected in 26 (72.2%) of 36 children with ongoing TP, 15 (48.4%) of 31 children with TP in the past, and 12 (66.7%) of 18 adults with TP. All children with high AAb ratios (greater than 5 times the control mean + 3 SD) were more than 8 years of age at diagnosis (mean age 12.4 years compared with 7.1 years in children with moderate or negative AAb levels; p = 0.003). The results suggest that the outcome for adolescents with high platelet-associated AAb levels may be similar to that of adults, whereas younger children may have a greater chance of spontaneous remission. The children with chronic TP in the past and elevated platelet-associated AAb levels may have a "compensated" TP and therefore may be at risk for relapses. Future studies aimed at serial AAb determination throughout the patients' courses may further define TP subgroups.