Haemostatic changes during hormone manipulation in advanced prostate cancer: a comparison of DES 3 mg/day and goserelin 3.6 mg/month.

Two hundred and fifty patients were entered into a randomized clinical study to compare the effectiveness of goserelin (Zoladex) in depot formulation with diethyl stilboestrol in locally advanced or metastatic prostate cancer. In 22 patients from the two arms of the study regular assessments were made of the effect of these hormone treatments on the haemostatic system. Selection of those patients with no recent surgical intervention and those on no drugs liable to interfere with the haemostatic mechanism was done at entry, in order to remove bias and achieve comparable groups. Baseline comparison of the two treatment groups showed no difference in clinical or biochemical measures of disease extent or activity, including serum prostate specific antigen (PSA) levels. There was a significant fall in plasma antithrombin-III (AT-III) activity in the DES treated group both from baseline and compared with the goserelin group. This effect commenced within 1 month and was maintained until monitoring ceased at 12 months. There was also a significant increase of fibrinolytic activity in the DES treated patients compared with those on goserelin. No divergence between the two treatment groups was seen in any other haematological parameters at baseline or on follow-up. A single AT-III estimation was also performed on a larger group of 74 patients at median follow-up time of 17 months (range 3-24). This confirmed the difference noted in the original study group. In the main study thrombotic episodes were noted in 13/126 patients treated with DES and 0/124 treated with goserelin (P less than 0.001). These findings suggest that lowered AT-III is the major factor through which DES affects the coagulation mechanism, and that no such effect is seen with goserelin treatment despite an equivalent therapeutic efficacy.

A human monocyte system for the assay of plasma opsonins.

Previous bioassays for studying the opsonic regulation of the monocyte-macrophage system are subject to a variety of serious disadvantages which limit their value. An assay system is described which avoids many of these pitfalls and is applicable to the rapid assay of large numbers of samples. Human monocytes were isolated from peripheral blood and Saccharomyces cerevisiae used as the target particle. Particle ingestion was assessed using an electronic particle size analyzer and a close correlation was shown between this assay and a visual assessment of ingested micro-organisms.

Long-term response in a patient with ITP following low dose anti-D immunoglobulin therapy.

A patient with chronic ITP relapsed after conventional therapy but following an infusion with low dose anti D (Rho) immunoglobulin, she entered a remission which has now lasted 10 months. This is difficult to explain on the basis of long term macrophage Fc receptor blockade and suggests an alternative mechanism of action.

Autoimmune thrombocytopenia: anti-glycoprotein IIb/IIIa auto antibodies are reduced after human anti-D immunoglobulin treatment.

In chronic autoimmune thrombocytopenic purpura (AITP), an indirect monoclonal antibody immobilised platelet antigen (MAIPA) assay detected serum glycoprotein (GP) IIb/IIIa antibodies in 16/39 (41%) cases. In patients with clinically active AITP, a direct MAIPA assay detected platelet-associated GP IIb/IIIa kantibodies in 8/13 (62%) cases. Platelet bound and serum antibody concentrations suggested a high antibody affinity for platelet membrane glycoprotein IIb/IIIa. Five AITP patients with platelet associated glycoprotein IIb/IIIa antibodies were treated with intravenous anti D immunoglobulin. All showed an increase in platelet counts and a decrease in platelet associated autoantibody. These responses could be due to immunosuppressive anti-idiotype antibodies in anti D immunoglobulin.

Psychological stress in nursing and medical staff on bone marrow transplant units.

There were 129 nurses and 26 doctors from 16 BMT centres in the UK who responded to a mailed survey of their job satisfaction, their psychological difficulties at work, the sources and effects of working stress, and any stress-reducing techniques they found useful. Half were emotionally exhausted, and 80% reported feelings of low personal accomplishment. A significant proportion, particularly medical staff, had marked feelings of depersonalisation. All aspects of job satisfaction were thought to be unsatisfactory (namely professional support or training). Signs of clinical anxiety were seen in > 10% of staff, and overt depression was present in 0.8% of nurses and 3.8% of doctors. Emotionally burnout developed because of work-related and personality factors. Sources of stress were found in regular work with dying patients excessive responsibility, rapid advances in transplant technology, and excessive personal demands of patient and families. The majority of staff had experienced difficulties in their personal lives which were directly linked to stress at work. The implications for both the patients and staff are discussed, and stress management techniques are suggested.

Gonadal function and psychosexual adjustment in male long-term survivors of bone marrow transplantation.

Gonadal function and psychosexual adjustment were evaluated in 29 male patients after autologous and allogeneic BMT (mean post-BMT time 35.6 months). Patients were divided into groups according to their interval from transplant in order to evaluate gonadal function throughout the post-BMT years. Thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were normal throughout the post-BMT years. Follicle-stimulating hormone (FSH) and luteinising hormone (LH) were increased throughout the years after BMT, suggesting moderate compensated hypogonadism. Hyperprolactinaemia was observed only in the 2nd year post-BMT and testosterone levels were normal, suggesting that Leydig cells can withstand alkylating agents or TBI. Psychosexual functioning in BMT survivors was compared with that of a group of mixed-diagnosis cancer patients (n = 30) and a group of healthy young subjects (n = 119). Long-term BMT survivors had similar psychosexual adjustment to that of other cancer patients who had received less intensive chemotherapy. Half the patients were dissatisfied with their current sex life. Major problems included impotence/erectile difficulties (37.9%), low sexual desire (37.9%) and altered body image (20.7%). However, both BMT survivors and cancer patients had significantly higher psychosexual dysfunction compared with healthy subjects. The type of chemotherapy, TBI (either single-dose or fractionated), type of transplant and post-BMT time did not correlate with either gonadal or psychosexual functioning.

Autologous bone marrow transplantation for patients with acute myeloid leukaemia and acute lymphoblastic leukaemia--a comparison.

Forty-two patients with acute leukaemia were treated with autologous bone marrow transplantation (ABMT) using a combination chemotherapy protocol for bone marrow ablation. The response to high-dose chemotherapy and ABMT and its associated morbidity and mortality have been compared in 24 patients with acute myeloid leukaemia (AML) and 18 patients with acute lymphoblastic leukaemia (ALL). In 16 patients with AML treated with ABMT during first complete remission (CR), ten patients (62.5%) remain in unmaintained remission; median follow up is 32 months. In eight patients with ALL treated in first CR, only one remains in remission 32 months post-ABMT, with three patients dying non-leukaemic deaths. Fourteen of 18 patients (AML and ALL) treated after first remission have died of recurrent leukaemia, two died non-leukaemic deaths and two remain well 31 and 55 months post-ABMT; both have ALL. The length of hospital stay and the amount of blood product support were similar in both groups. Haematological recovery post-ABMT was delayed in patients with AML compared to patients with ALL but this difference was not significant. Rapidly progressive lung infection was thought to be the cause of four early deaths (4/18) in patients with ALL but none in patients with AML. Severe gram-negative infections were significantly more common in patients with AML.

Quality of life in long-term survivors of marrow transplantation: comparison with a matched group receiving maintenance chemotherapy.

A retrospective descriptive study was designed to assess the quality of life (QoL) and psychosocial adjustment in long-term BMT survivors compared with a group of patients with haematological malignancies receiving maintenance chemotherapy (MC), matched for age, post-treatment time, sociodemographic and disease characteristics. The sample consisted of 91 long-term BMT survivors and 73 MC patients from three teaching hospitals in the UK. The results indicated that most of the BMT subjects had a good to excellent quality of life and, in some domains, even better adjustment than the MC patients. However, 20% of the BMT subjects had failed to return to full-time employment at a mean post-BMT time of almost 40 months. A significant number of BMT subjects were also identified with symptoms of anxiety and depression. The physical symptomatology had an association with psychological status. Impotence-related difficulties, decreased sexual satisfaction and altered body image were the main characteristics of psychosexual dysfunction in the BMT group. Poorer quality of life was predicted by the presence of depressive symptoms, low affirmation, and impoverished social adjustment.

Anti-i cold agglutinins in choriocarcinomatosis: trophoblastic i antigen.

The fetal antigen i has been demonstrated by indirect immunofluorescence on cord erythrocytes and placental trophoblast. A patient with disseminated choriocarcinoma developed high-tire anti-i cold agglutinins, and minor elevation of anti-i titres was seen in four out of six further patients with treated choriocarcinoma. In normal pregnant women, 6% showed similar increases in anti-i titres.

Fibronectin as an opsonic regulator of monocyte phagocytosis.

Experiments using human monocytes and the yeast Saccharomyces cerevisiae have shown that fibronectin is a major plasma opsonin. Further studies have shown that fibronectin promotes the ingestion as well as the adherence of micro-organisms. These observations are independent of the non-physiological concentrations of heparin used in other assay systems.

Ozone killing action against bacterial and fungal species; microbiological testing of a domestic ozone generator.

The action of ozone generated from a small domestic device was examined with a view to using it in clinical isolation units accommodating immunosuppressed patients. Over a six-hour period in an average size room the device did not generate sufficient ozone to suppress bacterial and fungal growth. A useful bactericidal action, against a variety of human pathogens was achieved with ozone concentrations between 0.3 to 0.9 ppm. Bactericidal ozone concentrations are close to the limit permitted for human exposure however and further experiments are indicated.

Myeloproliferative disorders: a paradox of in-vivo and in-vitro platelet function.

A patient with features of a myeloproliferative disorder developed an acute multisystems illness and died. In-vitro platelet aggregation was imparied, but necropsy revealed widespread platelet-rich thromboemboli and multiple organ infarctions. It is suggested that platelets are damaged during disseminated intravascular platelet aggregation (DIPA) and that disaggregation of platelet thrombi and recirculation of platelets give rise to their subsequent hypofunction when tested in vitro.

Circulating high molecular weight IgG fibronectin complexes in myeloproliferative disorders.

The plasma of patients with myeloproliferative diseases was examined by polyethylene glycol (PEG) precipitation, analytical ultracentrifugation, and immunoaffinity chromatography for the presence of high molecular weight complexes of IgG and fibronectin. Abnormal circulating high molecular weight material was identified by ultracentrifugation in all patients. This was precipitated by PEG and was shown by exclusion chromatography to contain IgG in a high molecular weight form. Examination of plasma by immunoaffinity chromatography supported previous evidence for complex formation between IgG and fibronectin. These findings are further evidence that abnormal high molecular weight IgG complexes are a prominent feature of myeloproliferative disorders and implicate IgG fibronectin complex formation.

Polycythaemia rubra vera transforming to acute lymphoblastic leukaemia with a common immunophenotype.

Lymphoblastic transformation of polycythaemia rubra vera is an extremely rare phenomenon. A case of a 76 year old man with polycythaemia rubra vera who developed acute lymphoblastic leukaemia (ALL) 16 years after his initial diagnosis is reported. Membrane markers showed a CD10 positive (common ALL) immunophenotype. To our knowledge this association has not been previously recorded. The rare occurrence of ALL in polycythaemia rubra vera may indicate that in a minority of patients clonal expansion of an abnormal pluripotent haemopoietic stem cell is responsible for the polycythaemia rubra vera disease phenotype.

Lymphoid aggregates in bone marrow: study of eventual outcome.

The practical importance of finding a morphologically benign lymphoid aggregate in the bone marrow of patients without known lymphoproliferative disease was assessed in 786 consecutive patients who had had 951 iliac crest bone marrow biopsies performed. Of these, 430 patients known to have lymphoproliferative disease at the time of biopsy were excluded. Of 356 patients, 86 (aggregate group) had at least one lymphoid aggregate in their biopsy specimen biopsy specimen (82 morphologically benign, three suspicious, and one malignant). Another 86 patients without aggregates (control group) were matched by age and sex. Both groups were followed up until death, or for a mean of 21.9 and 22.9 months, respectively, to assess their outcome. Eighteen (22%) of the 82 patients with morphologically benign lymphoid aggregates were later proved to have lymphoproliferative disease compared with none of the 86 control patients. Another 12 patients in the aggregate group and seven in the control group were suspected of having a lymphoproliferative disease on clinical grounds, so that altogether 30 (37%) and seven (8%), respectively, developed confirmed or suspected lymphoproliferative disease. In both cases the differences were highly significant (p less than 0.001). It is suggested that lymphoid aggregates in clinical biopsy material may not be a physiological finding and should alert pathologists or haematologists to the possibility of lymphoproliferative disease.

Composition of immune complexes and their relation to plasma fibronectin in chronic myeloproliferative disorders.

High concentrations of circulating immune complexes were detected by polyethylene glycol precipitation in 11 of 20 patients with myelofibrosis secondary to chronic myeloproliferative disease. Circulating immune complexes showed a positive correlation with plasma IgG concentrations both in patients and controls. Covariance analysis of the two groups showed significantly increased polyethylene glycol precipitable IgG in patients when adjusted for plasma IgG concentrations, indicating that the patients had significantly increased concentrations of complexed IgG. The immune complexes contained IgG, C3, and fibronectin and were inversely correlated with plasma fibronectin concentrations, suggesting that this major non-specific opsonin is important for the normal clearance of immune complexes. Therapeutic plasmapheresis efficiently removed circulating complexes and produced an increase in plasma fibronectin. This suggests that plasmapheresis may be useful for controlling immune complex mediated complications of these disorders.

Size of spleen rather than amount of platelet sequestration may determine long term responses to splenectomy in adult idiopathic thrombocytopenic purpura.

Fourteen adults with idiopathic thrombocytopenic purpura suffered a relapse after treatment with steroids, vinca alkaloids, or intravenous gammaglobulin. Splenic sequestration of platelets labelled with 111In-oxine was assessed, and the patients then underwent splenectomy. During follow up of four to 47 months (mean 20.7) none of the patients required further treatment, including three of 14 who showed partial relapses. Splenic sequestration patterns did not predict relapses, but an unexpected finding was that patients who relapsed had significantly smaller spleens. It is concluded that splenectomy is beneficial in most adult patients with idiopathic thrombocytopenic purpura and that radiological techniques to measure the size of the spleen may be useful in predicting which patients may relapse.

Two further cases of acute myeloid leukemia with trisomy 4.

Two cases of acute myeloid leukemia (FAB M1 and M2) with trisomy 4 are described. Morphologic abnormalities were confined to the granulocytic monocytic lineage with no evidence of erythroid or megakaryocytic involvement. One of the cases, who also had trisomy 13, presented initially with skin infiltration without bone marrow involvement.

Fractionated anthracycline therapy in acute myeloblastic leukaemia in adults.

A total of nine adults with newly diagnosed acute myeloblastic leukaemia (AML) and seven with relapsed disease were treated with fractionated daunorubicin in combination with cytosine arabinoside and 6-thioguanine. Remissions were seen in 89% and 57%, respectively. The side effects associated with bolus injections of daunorubicin were much less severe with fractionated treatment, and there was no significant cardiotoxicity despite total doses of up to 1363 mg/m2 daunorubicin. These results show that fractionated anthracyclines are effective in the treatment of AML and that this mode of administration may permit an upward revision of the accepted dose limits for anthracyclines.

Empirical treatment of febrile, neutropenic patients with tobramycin and latamoxef.

One hundred and two febrile episodes in neutropenic patients were treated with intravenous tobramycin and latamoxef. After 48 h latamoxef at 6 g day-1, patients were randomized to continue this regimen or latamoxef at 3 g day-1. Infections responded to these regimens in 67% and 71% of patients, respectively. Two-thirds of the infections which failed to respond were due to coagulase-negative staphylococci in Hickman catheters, a trend which may necessitate the inclusion of additional antibiotics in future empirical regimens. Prolonged prothrombin times due to antibiotic therapy were seen in nine patients but there was only one episode of bleeding and this responded quickly to treatment with vitamin K and fresh frozen plasma. In 35 patients, coagulopathy was present before antibiotics were started, and these cases also responded to vitamin K. The study shows that the response to tobramycin and latamoxef is comparable to other broad-spectrum antibiotic regimens and that a reduction in the dose of latamoxef after 48 h treatment may safely permit cost savings.