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Biomedical subjects

A Aronstam

Publications and source records attributed to A Aronstam.

At least 19 recordsLinked to original sources
PubMed1993

HIV infection in haemophilia--a European cohort.

Ten haemophilia centres in northern Europe have pooled data on 202 haemophilic children who were infected with HIV between 1979 and 1986. All cases were under 16 years of age on 1 July 1985. The age at infection ranged from 1-15 years. Thirty seven cases (18%) had progressed to AIDS by 1 July 1991 and 15 of these have died. Persistent generalised lymphadenopathy has been noted in 102 patients of whom 18 (17%) have developed AIDS. Twenty three of the remaining patients (23%) have not. CD4+ T cell counts have fallen steadily. Of 36 patients who have had shingles since seroconversion, 19 (53%) had counts below 0.2 x 10(9)/l. Thirty five out of 145 patients without shingles (24%) had similar values. The mean IgA concentration in patients with CD4+ T cell counts above 0.5 x 10(9)/l was 2.38 g/l, between 0.2 and 0.5 was 3.07 g/l, and in those with CD4+ T cell counts below 0.2 x 10(9)/l the mean IgA concentration was 4.58 g/l. Treatment patterns have altered between 1989 and 1991, with increased use of zidovudine in patients without AIDS and a marked increase in primary prophylaxis against pneumocystis pneumonia. This has been associated with a decline in the incidence of pneumocystis as an indicator disease in new AIDS cases from 56% in 1989 to 20% in 1991. These observations indicate that persistent generalised lymphadenopathy does not worsen the outlook, but shingles does. Rising IgA concentrations are markers for disease progression. Modern prophylactic regimens are delaying the onset of indicator disease, but CD4 values continue to fall steadily.

AIDS-Related Complex↗
PubMed1991

Relation between humoral responses to HIV gag and env proteins at seroconversion and clinical outcome of HIV infection.

OBJECTIVE: To study the contribution of the humoral response to HIV-I at seroconversion to disease outcome after 84 months. DESIGN: A retrospective longitudinal study. SETTING: Two haemophilia centres in the United Kingdom. PATIENTS: 88 Haemophiliac patients infected with HIV-I for whom sera were available from before seroconversion and in whom clinical follow up data were available. RESULTS: Kaplan-Meier survival analysis showed a significant difference between a high titre (greater than 1600) p24 antibody response at seroconversion and prolonged time before the development of HIV related disease (p = 0.0008). In contrast, higher titres of antibody to gp120 at seroconversion (greater than 25,600) correlated with more rapid clinical deterioration (p = 0.025). CONCLUSIONS: The first humoral response to HIV proteins at seroconversion is associated with clinical outcome; patients with an initial low titre antibody response to the gagp24 protein have a significantly faster rate of progression to CDC stage IV disease. Patients with a high titre p24 antibody response progress to AIDS more slowly, and these data provide an explanation why p24 antigenaemia is not universally detected in patients with AIDS. It is unclear whether the association between a strong initial p24 antibody response and slower progression of HIV disease is causal and if so whether it is due to viral or host factors.

Gene Products, gag↗
PubMed1990

Antibodies to HIV-1 nef(p27): prevalence, significance, and relationship to seroconversion.

A sensitive and specific enzyme-linked immunoassay for antibodies to the human immunodeficiency virus type 1 (HIV-1) nef gene product, p27, has been developed using recombinant Escherichia coli-derived protein from the LAV-1-Bru sequence. Of 92 HIV-1 infected hemophiliacs, 72 (78%) produced anti-nef antibodies in this assay; the early appearance of anti-nef prior to full seroconversion was a rare event in this population, occurring in only one subject (approximately 1%). Anti-nef antibodies were not detected in any of 500 sera from 98 repeatedly HIV seronegative subjects who had been exposed to sexually transmitted modes of HIV infection (45 subjects) or through blood products (53 subjects). There was no significant association of titer or anti-nef antibody with protection from disease in HIV infection (p = 0.1). Although the nef protein is relatively immunogenic in natural infection, this study cannot confirm the previously reported high prevalence of anti-nef antibodies prior to seroconversion, nor the finding of anti-nef antibodies in HIV seronegative but exposed subjects.

Cohort Studies↗
PubMed1990

Prevention of haemophilic arthropathy.

Early and adequate treatment of haemarthroses, will prevent or lessen future arthropathy. A prospective double blind controlled study of three different dose regimes of Factor VIII in the treatment of haemarthroses of the knees, elbows and ankles has shown that site and severity affect the initial response and should dictate the dose. High risk bleeds can be identified by the degree of movement loss and the presence of pain at rest, and tenderness. Reassessment of bleeds will indicate those not responding. Early recognition of delayed restoration of function requires an analysis of the normal processes. A study has revealed that the mean time for complete restoration of function was 3.6 +/- 3.3 days for elbows, 2.5 +/- 2.1 for knees and 1.1 +/- 0.9 for ankles. Departure from these norms should signal the need for early physiotherapeutic intervention.

Ankle Joint↗
PubMed1987

Early bleeding into upper limb muscles in severe haemophilia. Clinical features and treatment.

The clinical features, management and outcome of bleeding into the muscles of the upper limb of 44 patients are reported. Of 158 episodes of bleeding, 99% were treated within two hours of onset of symptoms and the mean time to complete restoration of function was 2.1 days. The most frequent site of bleeding was the deltoid muscle (24%), followed by the forearm flexors (23.5%), brachioradialis (19.5%), biceps (14%), forearm extensors (11%) and triceps (8%). The majority of bleeds presented with pain, either on movement or at rest, or with tenderness. Bleeds into the biceps required the most transfusions (mean 2.00) and took the longest to resolve (mean 4 days). Bleeding into the flexors and extensors of the forearm resolved most rapidly. The policy of early treatment has been shown to be effective in prompting early and complete recovery.

Adolescent↗
PubMed1986

Hemophilic patients with an inhibitor to factor VIII treated with high dose factor VIII concentrate. Results of a collaborative study for the evaluation of factor VIII inhibitor titer, recovery and half life of infused factor VIII.

The long term treatment of hemophilic patients with an inhibitor to Factor VIII has been difficult although some success with immunosuppressive agents has been reported. Eighteen hemophilic patients, mainly from Bonn in Germany, but also from other countries, have completed a high dose Factor VIII treatment in an attempt to reduce their inhibitor titer and induce "immune tolerance" to Factor VIII. Plasma samples from the 18 patients collected before and after infusion of 50 units Factor VIII/kg body weight were sent to five laboratories to evaluate inhibitor titer, Factor VIII recovery and half life. This collaborative study demonstrated a close correlation from one laboratory to another concerning inhibitor titration and Factor VIII recovery. The conclusion of the study is that all patients treated with this protocol showed an undetectable or low inhibitor titer against Factor VIII indicating that they can be efficiently treated with Factor VIII.

Adolescent↗
PubMed1985

The influence of D.D.A.V.P. on the survival of factor VIII in severe haemophiliacs.

The effect of D.D.A.V.P. (desamino-cys'-D-arg8-Vaso-pressin) on the survival characteristics of transfused VIII concentrate was studied in six severe, adolescent, haemophiliacs (VIII:C 1 iu/dl). D.D.A.V.P. was administered at a concentration of 0.3 ug/kg immediately following or 24 hours post infusion. No significant alteration in the half disappearance (1/2 d) or biological half-life (t 1/2) was detected for either VIII procoagulant (VIII:C) or its antigenic counterpart VIII:C Ag. As anticipated there was a significant (if sub-optimal) increase in VIII:R Ag within 2-4 hours of D.D.A.V.P. administration.

Blood Transfusion↗
PubMed1984

Clinical features of early haemarthroses in severely affected adolescent haemophiliacs.

Six hundred and ninety bleeds into the knees, ankles and elbows of severe haemophiliacs presenting for treatment within 3 h of the onset of symptoms have been studied with the aim of providing clinical information for the haemophiliac patient or his parent treating early bleeding episodes at home. Patients were resident at a boarding school and documentation and follow-up to complete resolution was possible. Stiffness was a presenting symptom in 61% of elbow bleeds, 49% of knee bleeds and 18% of ankle bleeds. Pain was a presenting feature in 79% of ankle bleeds, 55% of knee bleeds and 42% of elbow bleeds. Tenderness was a common feature of ankle bleeds (85%), less so in elbows (55%) and knees (69%). Swelling was a very common feature at all sites and the mean increases in girth of the knees, elbows and ankles were 1.42 cm, 0.88 cm, and 0.62 cm, respectively. All the knee and elbow bleeds and 85% of the ankle bleeds had demonstrable restriction of movement. There was a direct relationship between the degree of swelling, extent of movement restriction and time taken for complete restoration of function, the mean of which was 3.6 days for elbows, 2.5 for knees and 1.1 for ankles.

Adolescent↗
PubMed1983

A double-blind controlled trial of two dose levels of factor VIII in the treatment of high risk haemarthroses in haemophilia A.

One hundred and thirteen haemarthroses involving the knees, ankles and elbows of 29 severe haemophiliacs presenting with at least two of the risk factors, pain, tenderness, loss of more than 50% of movement and a delay of more than 3 h in treatment were studied. Each was given either a 20% or 40% dose of factor VIII and progress was then reviewed by medical staff unaware of the initial dosage. There was no significant effect on the retransfusion rate nor on the time to complete resolution. However, the difference between the percentage of patients showing residual movement restriction was significantly in favour of the high dose at 24, 36 and 48 h when all the bleeds were pooled and at 48 h for elbow bleeds.

Blood Transfusion↗
PubMed1983

The stability of VIII:C in frozen stored plasma samples--re-examined.

VIII procoagulant activity (VIII:C) was estimated by a two-stage assay method, on 100 pre- and post-transfusion samples obtained from severe haemophiliacs receiving regular treatment with a variety of VIII concentrate preparations. Close and significant correlation (r = 0.97 P less than 0.01) was obtained between freshly tested samples and samples stored for one month at -35 degrees C. No significant difference between the two samples was demonstrated by Student's paired-t-test. Forty-nine of the stored samples were also measured for VIII procoagulant antigen (VIII:C Ag) level. A similar close and significant correlation was found for this parameter (r = 0.9 P less than 0.01), when compared with the VIII:C of the freshly tested samples. On average the VIII:C Ag value was 10% lower than the corresponding VIII:C value, although the difference was not statistically significant.

Antigens↗
PubMed1983

The clinical features of early bleeding into the muscles of the lower limb in severe haemophiliacs.

The clinical features, management and outcome of 178 early bleeding episodes into the musculature of the thigh and lower limb of 37 severe haemophiliacs are reported. Ninety-five per cent of all bleeds were treated in under three hours from onset of symptoms and the mean time to complete restoration of function was 3.5 days. The most frequent site of bleeding was the quadriceps (44 per cent) followed by the calf (35 per cent), anterior tibial compartment (seven per cent), adductors of the thigh (seven per cent), hamstrings (six per cent) and sartorius (one per cent). Bleeds of the quadriceps took longest to resolve (mean, four days), significantly longer than bleeds of the calf muscle (3.1 days). The first symptom in 66 per cent of bleeds was pain on movement. When the quadriceps was involved, this rapidly progressed to pain at rest. There was a significant prolongation of recovery time when bleeds of this muscle group were treated more than two hours after the onset of symptoms. Bleeds of the calf muscle required less transfusions and no prolongation in recovery time occurred in bleeds treated up to three hours from the onset of symptoms. The results of this study contrast markedly with earlier reports based on later presentations.

Blood Transfusion↗
PubMed1982

An examination of joint laxity in haemophilia.

An adolescent haemophiliac group (all less than 1 per cent Factor VIII) and a normal, similarly aged, 'control group' of boys were examined to measure joint laxity in an effort to identify a causative factor for bleeding. Definitive laxity was found in the thumb joints and in finger extension of haemophiliacs compared with normal boys. The haemophiliacs who were more lax-jointed showed no tendency towards an increased number of bleeds when they were followed for 100 days. Possible explanations for these phenomena are discussed.

Adolescent↗
PubMed1982

The identification of high risk knee bleeds in adolescents with severe haemophilia A.

One hundred and thirty-seven knee bleeds treated with an initial dose of 11-16 units of factor VIII/kg have been reviewed in an attempt to find the predictive factors for bleeds requiring retransfusion. Thirty-two bleeds (23.4%) were retransfused within 48 hours because of extension of bleeding or poor progress. Fifty-nine per cent of bleeds which were retransfused presented with pain and 72% were tender at presentation. These figures contrasted with those for bleeds which were not retransfused of 30% and 45%. The difference in each case is significant. Forty-seven per cent of retransfused bleeds presented with less than 50% of normal movement against 12% who were not retransfused. This difference was also highly significant. It is suggested that knee bleeds presenting with pain, tenderness and/or more than 50% restriction of movement should be considered for higher initial doses of factor VIII.

Adolescent↗
PubMed1982

The use of an activated factor IX complex (Autoplex) in the management of haemarthroses in haemophiliacs with antibodies to factor VIII.

A new activated factor IX product (Autoplex) has been used for the treatment of 18 haemarthroses in three haemophiliac patients with antibodies to factor VIII and a history of high anamnestic response to challenge with factor VIII. Results were evaluated by assessing pain, tenderness, range of movement and girth at 8 and 24 hours. A score of 2 was given for improvement at 8 hours and 1 for improvement at 24 hours. The result was expressed as a percentage of the possible score. Nine episodes treated with less than 35 units of Autoplex/kg had a mean score of 52% and nine episodes treated with more than 35 units/kg had a mean score of 73%. When only the more severe group of bleeds was considered, an even more marked dose related response emerged. When the ratio of the percentage fall in the PT to the percentage fall in the KCCT was plotted against the outcome, a significant correlation emerged (r = 0.43; P = 0.02).

Adolescent↗