Search PubMed⌕ Search

Biomedical subjects

P Jacobs

Publications and source records attributed to P Jacobs.

At least 379 records · Page 21Linked to original sources
PubMed1986

Prolonged remission of severe refractory rheumatoid arthritis following allogeneic bone marrow transplantation for drug-induced aplastic anaemia.

Aplastic anaemia developed in a 33-year-old woman whose rheumatoid arthritis was refractory to the administration of many drugs, including penicillamine and gold. Allogeneic bone marrow transplantation reversed the haematological abnormality and simultaneously resulted in a 2-year period of relief from joint pain. Symptoms then reappeared and the serological tests for rheumatoid arthritis again became positive. The arthralgia has responded slowly to the administration of anti-inflammatory drugs and steroids. The protracted asymptomatic period may have been due to the intense immunosuppression required for marrow grafting and the subsequent administration of cyclosporin. Since she developed chronic graft-versus-host disease, the arthritis may be an unusual complication of this syndrome.

Adult↗
PubMed1986

Results of treatment in immune thrombocytopenia.

One hundred and forty-eight adults with immune thrombocytopenia attending a single institution between 1971 and 1981 were analysed retrospectively and observed for a minimum of three years. Prednisone was administered to 134 patients (90 per cent) in whom a peak platelet count occurred at a median of eight days, at which time four distinct patterns of response became evident: 20 patients (15 per cent) achieved complete remission with platelet counts greater than 200 X 10(9)/I, and of these 13 relapsed; 46 (34 per cent) had incomplete remission with platelet counts between 100 and 200 X 10(9)/I, and of these 38 relapsed; 22 (17 per cent) had a partial remission with platelet counts between 50 and 100 X 10(9)/I, and 14 have relapsed; the remaining 46 (34 per cent) failed to respond to prednisone. The addition of cytotoxic drugs for patients who relapsed or failed to respond to this agent was uniformly ineffective with the spleen in situ. One hundred and two patients underwent splenectomy without mortality, and peak platelet counts were achieved at a median of two days after the operation. Forty-one patients (40 per cent) achieved complete remission and four have relapsed; 36 (35 per cent) achieved incomplete remission and five have relapsed; 18 (18 per cent) had a partial remission and two have relapsed; treatment failed in seven (7 per cent). Eleven of the post-splenectomy patients relapsed in a median of four months. Together with the seven who failed to respond (n = 18), a subgroup of 17 was treated with immunosuppressive regimens including prednisone, azathioprine, cyclophosphamide or vincristine. Ten achieved stable although incomplete remissions, with platelet counts between 50 and 200 X 10(9)/I. We suggest that the treatment of immune thrombocytopenia in the adult initially should be a course of prednisone, from which complete remission rate will be 4.7 per cent and further incomplete remissions of 5.5 per cent and partial remissions of 8.5 per cent can be anticipated; no correlation was demonstrable with the duration of symptoms and response to prednisone. Symptomatic patients and those requiring unacceptable doses of adrenocorticosteroids should then proceed to splenectomy, when an overall response rate of 93 per cent is possible. A relapse rate of 11 per cent may require a limited course of immunosuppressive treatment, which is likely to be effective in approximately 75 per cent of these individuals.

Adolescent↗
PubMed1985

The effects of cytoskeletal inhibitors on intestinal iron absorption in the rat.

An established and validated method using loops of intestine in vivo in rats was used to study the effects of cytoskeletal inhibitors on iron absorption. Radioactive iron instilled into the loop of intestine pretreated with test substance was monitored in the blood and, after death, ferritin loading with radioactive iron was measured on density gradients of mucosal cell homogenates and absorbed iron in the carcass was determined. Colchicine, vincristine and cytochalasin B all caused dose- and time-dependent inhibition of iron absorption, and the effects of cytochalasin B were reversible within 1 h. It is not known which cellular component is the vehicle for the transcellular movement of iron from the intestinal lumen onto plasma transferrin; however, this study showed that the uptake of iron by ferritin in an iron-absorbing loop of intestine paralleled the actual absorption of iron into the carcass. This phenomenon did not occur in non-iron-absorbing intestinal and was inhibited by the action of the cytoskeletal inhibitors in the iron-absorbing region. Previously we had shown that iron uptake into cells and onto cellular transferrin was virtually the same throughout the small intestine, irrespective of the iron-absorbing capacity of the region. The results of this study therefore suggest that iron absorption depends on an intact cytoskeletal system and that ferritin in the iron-absorbing cell is able to load from the pool of iron committed to transcellular movement onto plasma transferrin.

Animals↗
PubMed1985

Micro-angiopathic haemolytic anaemia and an unusual lactate dehydrogenase iso-enzyme pattern in metastatic adenocarcinoma. A case report.

Micro-angiopathic haemolytic anaemia is an unusual but well-recognized complication of metastatic adenocarcinoma. A young black man presented with red cell fragmentation, compensated disseminated intravascular coagulation and leuco-erythroblastosis. Metastatic adenocarcinoma of the stomach was suspected but only demonstrated at autopsy. An unusual finding was the elevation of the slow-moving lactate dehydrogenase iso-enzyme (LDH5) level in the plasma which was shown to be produced by metastatic tumour cells recovered from the bone marrow.

Adenocarcinoma↗
PubMed1985

VP-16-213 in the treatment of stage III and IV diffuse large cell lymphoma.

Between 1975 and 1979, 81 consecutive patients with clinical Stage III or IV diffuse large cell lymphoma were randomized to prospectively receive the epipodophyllotoxin VP-16-213 as a single agent (Group 1: n = 25), or an equivalent quantity of the same drug combined with either cyclophosphamide (Group 2: n = 24), or doxorubicin (Group 3: n = 32). In previously untreated patients complete remission rates were 55% for Group 1, 29% for Group 2, and 62% for Group 3, with further partial remission in 22%, 12%, and 13%, and overall median survival for the three groups being 19 months, 5 months, and 19 months, respectively. There was no difference between Group 1 and Group 3, whereas the cyclophosphamide-containing regimen (Group 2) was clearly inferior (P less than 0.01). Survival was adversely affected by failure to achieve complete remission, prior chemotherapy, and the presence of high bulk disease. No statistically significant correlation could be demonstrated between survival and histologic subtype, differences between Stage III and IV disease, and invasion of either the bone marrow or gastrointestinal tract. The epipodophyllotoxin VP-16-213 is an active agent in patients with advanced stages of diffuse large cell lymphoma. The inferior results obtained when combined with cyclophosphamide remain unexplained. The inclusion of previously treated patients in the series suggested a superiority for combining the epipodophyllotoxin VP-16-213 with doxorubicin, since a higher percentage achieved complete remission, median duration of survival was longer, and a great number of individuals remain disease-free. When re-analysed excluding previously treated patients, these differences are no longer evident and the combination is not statistically superior to the epipodophyllotoxin alone.

Alopecia↗
PubMed1985

T-cell acute lymphoblastic leukaemia in adults.

Of 27 consecutive adult patients with acute lymphoblastic leukaemia (ALL), 7 had T-cell variants on the basis of sheep erythrocyte (E) rosette formation; in 5, a characteristic thymic phenotype was demonstrated by the use of appropriate monoclonal antibodies. All patients were treated with prednisone, vincristine, 1-asparaginase and adriamycin and the peripheral blood cleared of circulating lymphoblasts in a median of 8 days (range 6 - 45 days), a figure which does not differ significantly from that of 7 days (range 3 - 59 days) in those with the common ALL (P greater than 0,5). The complete remission rates were 71% for the patients with T-cell leukaemia and 75% for the E rosette-negative patients; median durations of remission were 35 and 26 weeks respectively and the actuarially predicted median durations of survival were 49 and 39 weeks respectively. Therefore the presence of T-cell markers in adult ALL does not seem to affect the prognosis in the same way that it does in children, and this is likely to be the result of the more aggressive clinical course of ALL of all phenotypes in adults.

Adolescent↗
PubMed1985

Life-threatening haemolytic anaemia and infectious mononucleosis. A case report.

A 36-year-old man with infectious mononucleosis presented with massive intravascular haemolytic anaemia. The diagnosis was established by a positive Paul-Bunnell test, the demonstration of IgM antibodies against Epstein-Barr virus capsid, and IgG antibody to early antigen. The direct and indirect antiglobulin tests were negative; the pathogenesis of the severe haemolysis was attributed to the temporary synthesis of anti-i cold agglutinin having a high thermal amplitude. Although life-threatening, the episode was short-lived and responded to supportive therapy with blood transfusion and folate administration only. This case illustrates a rare association between severe haemolytic anaemia and infectious mononucleosis, it emphasizes the value of IgM-specific fluorescent antibody tests in diagnosis when patients have otherwise unexplained haemolysis.

Adult↗
PubMed1985

Cyclophosphamide-related intravascular haemolysis during continuous-flow plasma exchange.

The plasma of a patient being prepared for allogeneic bone marrow transplantation was found to be severely lymphocytotoxic to donor cells. Three isovolaemic plasma exchanges carried out using a continuous-flow technique were required to reduce this titre to undetectable levels. Neither these procedures nor pretransplantation conditioning of the patient with 60 mg/kg or cyclophosphamide on two consecutive days resulted in overt haemolysis. However, a single identical plasmapheresis 12 hours after completing the second dose of the alkylating agent resulted in profound intravascular haemolysis requiring red cell transfusion. Subsequent studies in five patients receiving the same cyclophosphamide regimen demonstrated that red cell life span, when measured with radiochromium, was reduced from a normal of 25-35 days to a median of 11.5 days. Further studies in the same five patients carried out simultaneously demonstrated that red cell fragility, when assessed in vitro with osmotic or mechanical stress, was marginally increased but became clearly abnormal in only one individual. These doses of cyclophosphamide may result in accelerated but subclinical red cell destruction, and plasma exchange in this period may be associated with rapid intravascular haemolysis. This complication should now be added to the list of those that can occur when plasmapheresis is required in this specific clinical situation.

Adult↗
PubMed1985

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↗
PubMed1985

The epipodophyllotoxin VP16-213 in combination chemotherapy for adults with acute nonlymphoblastic leukaemia.

A total of 232 previously untreated adults with acute nonlymphoblastic leukaemia were consecutively entered into four successive studies. In the first, complete remission rates and survival were inferior to a group treated on the same regimen in London, suggesting population differences, possibly on the basis of late referral and poor nutritional status. In the second study the addition of the epipodophyllotoxin VP16-213 to conventional doses of doxorubicin and cytosine arabinoside improved complete remission rate and median duration of survival. In the third study this induction programme was unchanged and short duration of intensification was compared with an extended period, but no statistically significant difference was demonstrated. In the fourth study, which is currently active, the role of the epipodophyllotoxin VP16-213 (Cape Town Regimen/CTR III) was compared with the same two agents in combination with thioguanine (DAT), but to date no difference in remission rate or survival is evident. Four conclusions are supported by data from these studies. First, the addition of VP16-213 to doxorubicin and cytosine arabinoside improves complete remission rate, prolongs median duration of complete remission and survival, with shortening of the time taken to achieve this status in our population. Second, evidence to date shows no advantage for the DAT programme containing thioguanine over CTR III in which this latter agent is replaced by the epipodophyllotoxin VP16-213. Third, there is no statistically significant difference in survival once patients have achieved complete remission following randomisation to receive 6 months in comparison with 15 months of intensification therapy. Finally, of the previously described prognostic factors, only response to initial chemotherapy has proved significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1985

Effects of molsidomine on hemodynamics and blood gases in acute myocardial infarction with left heart failure.

We studied the effects of molsidomine on hemodynamic properties and blood gas levels in eight patients with acute myocardial infarction and left heart failure. One hour after an 8 mg intravenous bolus injection, pulmonary wedge pressure and right atrial pressure decreased, respectively, from 30 +/- 9 to 23 +/- 12 mm Hg (p less than 0.01) and from 10.4 +/- 3.6 to 7.8 +/- 4.0 mm Hg (p less than 0.05) without significant changes in heart rate, cardiac index, or systemic blood pressure. There was a mild decrease in arterial oxygen tension (from 61 +/- 15 to 56 +/- 6 mm Hg), but it was not significant. The drug induced no adverse effects. Intravenous bolus injection of molsidomine rapidly relieves pulmonary congestion in patients with acute myocardial infarction.

Aged↗
PubMed1985

Immunophenotypic classification of lymphoblastic leukaemia and lymphocytic lymphoma--an experience in the south-western area of the Cape Province of South Africa.

Adequate tumour material was obtained for phenotypic classification using a standard library of monoclonal antibodies from 81 previously untreated patients with acute lymphoblastic leukaemia (ALL), chronic lymphocytic leukaemia (CLL), or lymphocytic lymphoma (LL). Sixty-one individuals were adults and 20 were children of 14 yr or younger. Fifty-eight of the patients (72%) had acute lymphoblastic leukaemia and the remaining 23 (28%) had chronic lymphocytic leukaemia or lymphocytic lymphoma. Considering only the patients with acute lymphoblastic leukaemia (n = 58) the median age was 19 yr (range 3-69 yr): 9% were black, 43% were coloured, 48% were white, and the distribution between adult (n = 38) and paediatric patients (n = 20) was comparable. Complete remission rate in the adults was 58% and in the paediatric group 85%. For the total group (n = 58) median duration of survival was 59 weeks for common, 39 weeks for null, 63 weeks for T-ALL, and 13 weeks for B-ALL subtypes. In both the common and the null groups overall and disease-free survival was superior in the children. In contrast, no difference was evident in the T-ALL group, which was also notable for its high incidence in young coloured males. The 15 patients with CLL and eight with LL were adults and all the cells were phenotypically of B lineage: in view of the small numbers no comments are possible about ethnic differences. A multi-centre collaborative study is needed to define the epidemiology of haematologic malignancy in South Africa, with emphasis on differences among ethnically distinct subpopulations.

Adolescent↗