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Biomedical subjects

M Contreras

Publications and source records attributed to M Contreras.

At least 199 records · Page 11Linked to original sources

Neonatal alloimmune thrombocytopenia.

Neonatal alloimmune thrombocytopenia (NAIT) occurs when maternal alloantibodies to antigens present on fetal platelets cause their immune destruction resulting in thrombocytopenia in the newborn infant or fetus. Bleeding may be severe; intracranial haemorrhage and permanent neurological damage are the most serious complications. Despite the severity of the disease, there is often a delay in making the correct diagnosis and instigating appropriate treatment. Recent evidence that NAIT is more common than has previously been recognised, a better understanding of the molecular basis of platelet serology and advances in technology, which have made it possible to take blood samples from fetuses and transfuse them in utero, have all contributed to a growing interest in this condition. In addition, it is exciting to realise that an aggressive approach to the management of established cases and 'at risk' pregnancies can prevent serious neurological sequelae and dramatically improve the outcome for affected infants.

Antigens, Human Platelet↗

Maternal alloimmunization to HLA, platelet and granulocyte-specific antigens during pregnancy: its influence on cord blood granulocyte and platelet counts.

In order to obtain an estimate of the frequency of platelet-specific and granulocyte-specific antibodies and of the effect of such antibodies on the platelet count and granulocyte count of the newborn infant, serum from 147 women in their second or subsequent pregnancies was tested. No platelet-specific antibodies were found but 29 of the women had granulocyte-specific antibodies and the corresponding infants had granulocyte counts which were significantly lower than those of infants without antibodies. HLA antibodies were found in the sera of 57 women but were not associated with diminished platelet or granulocyte counts in the corresponding infants. Maternal granulocyte antibodies may be an underestimated contributory factor in the pathogenesis of neonatal neutropenia.

Blood Platelets↗

Should anti-Rh immunoglobulin be given D variant women?

D variant women occasionally form anti-D during or following pregnancy with a D-positive fetus. It is not known whether Rh immunization could be suppressed by using anti-Rh immunoglobulin (Rh Ig), or whether the injected antibodies would be absorbed by the woman's D variant cells. In order to predict the likely outcome, three anti-Rh Ig preparations were absorbed independently with five examples of D variant red cells: R1VIr (n = 3), R1Br (n = 2), and with cells of common Rh-positive and Rh-negative phenotypes: R0, r'r, r"r or rr cells (n = 1 each). The titres of the Ig preparations against all these cells were compared after three, six, nine and 12 absorptions. The titres of the unabsorbed anti-Rh Igs against R0 cells ranged from 2(15) to 2(18). Anti-D activities were hardly affected by absorption with r'r, r"r or rr cells, but were completely exhausted after three to six absorptions with R0 cells. Most of the D variant cells were as ineffective as rr cells in reducing anti-D activity against R0 cells, but one R1VIr variant produced a fall in titre against R0 cells, equivalent to four or five doubling dilutions after three to six absorptions, which could not be reduced further by subsequent absorptions. Therefore, a substantial proportion of the anti-D in the immunoglobulin preparation does not bind to D variant red cells. The component of the anti-D that does not bind to D variant cells would be expected to be present in the circulation of D variant individuals injected with anti-Rh immunoglobulin, and should be effective in suppressing Rh immunization. An increased dose of the anti-Rh Ig might have to be administered in order to allow for the fraction that can bind to D variant red cells and which would not be available for immunosuppression.

Absorption↗

The Rh-negative donor.

By typing fully for Rh, donor samples found to be D-negative but C-positive and/or E-positive on the Kontron Groupamatic G2000, the incidence of Ccddee (r'r) was found to be 0.44%, ccddEe (r"r) 0.50% and Du 0.30%. A total of 15,000 samples typed on the Groupamatic as D-, C- and E-negative were tested by an antiglobulin technique for Du, but none was found to be positive. A new strategy was therefore adopted for routine Rh typing of donations that includes typing first-time donors on the Groupamatic for C, D and E antigens; those that type as D-negative, C-positive and/or E-positive are further tested but no routine Du testing of D-, C- and E-negative donations is performed. Donations are labelled according to their D type, and the once used terminology 'Rh-positive donor, Rh-negative recipient' is no longer used except for those rare Rh D-positive donors belonging to the D category VI of Tippett & Sanger (1962).

Blood Banks↗

Provision of a panel of anti-toxoplasma-negative blood donors.

Toxoplasma gondii has been reported to cause complications only in immunosuppressed patients receiving leucocyte transfusion, when severe acute toxoplasmosis has been reported with associated mortality. At the North London Blood Transfusion Centre (NLBTC) we have screened 392 plasmapheresis donors (using toxoreagent latex agglutination test manufactured by Eiken) to provide a panel of blood donors negative for antibody to toxoplasma for seronegative recipients. A toxoplasma-negative panel of donors would only be required for those rare instances when granulocyte concentrates are indicated for transfusion of seronegative recipients. The toxoreagent test classified the 392 blood donors as 36% positive, 23% weakly reactive and 41% negative; these negative sera were retested with toxoreagent and 17% of them reacted weakly but none were positive. The toxoreagent 'weakly-reactive' sera (all of which were Sabin-Feldman dye test negative) can probably best be accounted for by the exacting screening conditions under which we operated to ensure seronegativity in our special donor panel. 40% of the antibody-positive donors were female and 34% male. Seropositivity increased with age.

Adult↗

Gelatin particle agglutination assay for HIV antibodies: a rapid, economical modification with increased sensitivity.

Modification of a commercial gelatin particle agglutination assay for anti-HIV reduces the test time to 30 min, increases the sensitivity sevenfold without any prozoning, and maintains specificity while cutting the cost of the test by 90%. The modification involves a tenfold dilution of the gelatin particles, which are added to a dilution of test serum in a 'V' well standard microplate. After incubation, plates are centrifuged briefly and allowed to stand at an inclination of 70 degrees until positive and negative reactions are clearly distinguishable within approximately 15 min.

Agglutination Tests↗

Consequences of fetomaternal haemorrhage after intrauterine transfusion.

Fetomaternal haemorrhage was studied after 68 consecutive fetal intravascular transfusions performed in 20 patients with Rh isoimmunisation. alpha Fetoprotein concentration was assayed in maternal blood taken before, and immediately after each transfusion and three and 24 hours later. An increase of 50% or more in the concentration in any of the samples after transfusion was considered to indicate fetomaternal haemorrhage. Fetal alpha fetoprotein concentration in blood sampled before transfusion was also assayed and the amount of fetomaternal haemorrhage calculated. Fetomaternal haemorrhage occurred in 21 of 32 patients with an anterior placenta and in six of 36 with a posterior or fundal placenta. The mean estimated volume of haemorrhage was 2.4 ml, which was on average equal to 3.1% of the total fetoplacental blood volume. When the volume of fetomaternal haemorrhage at the first transfusion was greater than 1 ml there was a greater increase in maternal Rh (D) antibody titres and a greater fall in fetal packed cell volume. Sampling of fetal blood should not be routinely done early in patients with Rh isoimmunisation, and intrauterine transfusion should be delayed as long as possible. Sampling sites other than the placental cord insertion reduces the risk of fetomaternal haemorrhage.

Blood Transfusion, Intrauterine↗

Tuberculous ulcer of the skin.

A case of tuberculous skin ulcer is reported. The biopsy specimen did not reveal acid-fast bacteria but cultures grew Mycobacterium tuberculosis. A high index of suspicion is needed to diagnose mycobacterial ulcers correctly. The classification of the cutaneous tuberculoses is discussed.

Adult↗

Peroxisomal lignoceroyl-CoA ligase deficiency in childhood adrenoleukodystrophy and adrenomyeloneuropathy.

We previously reported that in childhood adrenoleukodystrophy (C-ALD) and adrenomyeloneuropathy (AMN), the peroxisomal beta-oxidation system for very long chain (greater than C22) fatty acids is defective. To further define the defect in these two forms of X chromosome-linked ALD, we examined the oxidation of [1-14C]lignoceric acid (n-tetracosanoic acid, C24:0) and [1-14C]lignoceroyl-CoA (substrates for the first and second steps of beta-oxidation, respectively). The oxidation rates of lignoceric acid in C-ALD and AMN were 43% and 36% of control values, respectively, whereas the oxidation rate of lignoceroyl-CoA was 109% (C-ALD) and 106% (AMN) of control values, respectively. On the other hand, the oxidation rates of palmitic acid (n-hexadecanoic acid) and palmitoyl-CoA in C-ALD and AMN were similar to the control values. These results suggest that lignoceroyl-CoA ligase activity may be impaired in C-ALD and AMN. To identify the specific enzymatic deficiency and its subcellular localization in C-ALD and AMN, we established a modified procedure for the subcellular fractionation of cultured skin fibroblasts. Determination of acyl-CoA ligase activities provided direct evidence that lignoceroyl-CoA ligase is deficient in peroxisomes while it is normal in mitochondrial and microsomes. Moreover, the normal oxidation of lignoceroyl-CoA as compared with the deficient oxidation of lignoceric acid in isolated peroxisomes also supports the conclusion that peroxisomal lignoceroyl-CoA ligase is impaired in both C-ALD and AMN. Palmitoyl-Coa ligase activity was found to be normal in peroxisomes as well as in mitochondria and microsomes. This normal peroxisomal palmitoyl-CoA ligase activity as compared with the deficient activity of lignoceroyl-CoA ligase in C-ALD and AMN suggests the presence of two separate acyl-CoA ligases for palmitic and lignoceric acids in peroxisomes. These data clearly demonstrate that the pathognomonic accumulation of very long chain fatty acids in C-ALD and AMN is due to a deficiency of peroxisomal very long chain (lignoceric acid) acyl-CoA ligase.

Adrenoleukodystrophy↗

Antiparasitic activity of nine pyrazole derivatives against Trichomonas vaginalis, Entamoeba invadens and Plasmodium berghei.

Nine nitropyrazole derivatives were prepared and tested against Trichomonas vaginalis in vitro and in vivo, Entamoeba invadens in vitro and Plasmodium berghei in vivo. Three of the compounds, 4-4-nitropyrazole, 1-methyl-4-nitropyrazole and 4,4'-dinitro-1,1'-methylenedipyrazole, have an activity similar to that of metronidazole (used as the reference compound) against T. vaginalis and E. invadens after 48 hours of incubation. All the compounds tested were inactive against P. berghei.

Animals↗

Induction of red blood cell destruction by graft-derived antibodies after minor ABO-mismatched heart and lung transplantation.

Heart-lung transplantation (HLT) unlike other solid-organ transplants involves transplantation of a large amount of lymphoid tissue; hence there is considerable potential for graft-versus-host reaction if there is an antigen mismatch between donor and recipient. Due to the shortage of suitable donors, minor ABO-mismatched HLT (group O organs given to A, B, or AB recipients) are performed. Of 84 consecutive HLT at Harefield Hospital, nine fully ABO-matched and nine ABO-mismatched HLT were studied. Six minor ABO-mismatched HLT patients had evidence of immune destruction of recipient's red cells. Haemolysis started from days 4-12 and lasted for a mean of 13 days; in four cases transfusion support was necessary. ABO antibodies incompatible with the recipient ABO antigens, but compatible with the donor, were found in the serum and red cell eluates of these patients. In two cases, these antibodies were detected for over one year after transplantation. These changes were not seen in the fully ABO-matched controls. Our findings suggest that donor-derived lymphocytes from group O organs continue to produce anti-A and/or anti-B after transplantation, and if the recipient is group A, B, or AB, mount a secondary immune response following antigenic stimulation by the recipient's differing ABO antigens. The specific transfusion management of these patients is discussed.

ABO Blood-Group System↗

A prospective study of the incidence of delayed haemolytic transfusion reactions following peri-operative blood transfusion.

Delayed haemolytic transfusion reactions (DHTRs) are a recognized sequel of blood transfusion. The true incidence and importance of this complication have been difficult to estimate due to the lack of any prospective studies. We have carried out such a study by testing 530 patients who were transfused during cardiac surgery. 2% of the patients had new red cell alloantibodies detectable 1 week following transfusion. Despite this finding, and the fact that at the time the study was performed pre-transfusion antibody screening of recipients was not routine practice, no DHTRs were diagnosed on clinical or laboratory criteria. These results indicate that the reported incidences, based on retrospective recognition of DHTRs, are not a serious underestimate of the frequency of the complication.

Adolescent↗

Partial characterization of a nuclear proteolytic activity from fertilized sea urchin eggs.

The nuclei from fertilized sea urchin eggs, obtained 80 min after fertilization, contains a neutral proteolytic activity. Optimal action on casein was observed at pH 7-8 and a Km value of 1.2 mg/ml was determined for this substrate. The proteolytic activity was stimulated 1.5 fold by the addition of 3 M urea and decreased at higher urea concentrations. NaCl and CaCl2 were inhibitory whereas MgCl2 increased the enzyme activity. Isolated histones from sea urchin sperms, and especially histones H1, H2A, H2B and H3, were degraded by the nuclear activity. A partial inhibition of histones degradation was caused by sodium bisulfite and NaCl. The proteolytic activity was found associated to the chromatin of fertilized sea urchin eggs.

Animals↗