Search

Abnormalities of blood coagulation associated with neoplasia may be important in the pathogenesis of tumour spread. Most patients with advanced malignancy have evidence of activated coagulation, but the mechanisms underlying this are unclear. We have examined in vitro monocyte procoagulant activity and compared this to plasma levels of fibrinopeptide A, in 52 patients with clinically localised breast cancer. Patients with localised breast cancer and activated coagulation displayed a strong positive correlation between monocyte procoagulant activity and level of fibrinopeptide A(r = +0.86, p less than 0.001). No such relationship was demonstrated in a smaller number of patients with metastatic breast cancer. It is concluded that monocyte procoagulant activity plays an important role in coagulation activation in patients with localised breast cancer. The implications of this for adjuvant anticoagulant therapy in breast cancer are discussed.

Agents activating human plasminogen have been prepared from a variety of human sources, namely plasma, blood vessel endothelium and tissue. Their physical and functional properties have been found to differ from that of the urinary activator, urokinase. Antiserum to urokinase, while it quenched the activity of urokinase itself, had no effect on the activity of the plasma, endothelial or tissue activators.

30 consecutive patients with acute leukaemia were studied prior to commencement of treatment in order to assess the incidence and significance of raised elastase (ELP) - alpha 1 antitrypsin complex level. In addition the reliability of detecting low factor XIII subunit levels as an indicator of in vivo release of ELP was evaluated. While 15 patients had raised levels of ELP alpha 1 antitrypsin complex levels, only 4 of these had reduced levels or factor XIII subunits A and S. In addition increased levels of ELP- alpha 1 antitrypsin complex were not associated with any marked disturbance of routine coagulation tests. Patients with raised ELP- alpha 1 antitrypsin complex levels had significantly higher circulating white cell and blast cell counts as compared to those patients with normal levels of this complex. In patients entering remission the levels of ELP- alpha 1 antitrypsin complex returned to normal.

Following infection of RN2 rat Schwannoma cells with unfiltered JHMV inocula, a cell line with an altered phenotype evolved, which was shown to be a somatic cell hybrid of RN2 and mouse L-2 cells. This cell line, EJ, persistently yields JHMV at titres greater than 10(6) pfu/ml and does not show the suppression of virus production at 39.5 degrees C that is characteristic of a persistently infected RN2 line. Intracellular viral nucleocapsids are demonstrated. Cloning of EJ hybrids yields cell lines that show a variety of responses to infection by JHMV or MHV3.

Forty six lymph nodes were examined with the indirect immunoperoxidase technique for the distribution of fibronectin and laminin. Fibronectin was present in the framework of the tissue and the basal lamina of blood vessels, giving a clear outline of nodal architecture. Intracellular fibronectin was observed in cases of reactive sinus histiocytosis, when about a third of macrophages exhibited strong positivity. Mast cells were positive. A pronounced increase in extracellular fibronectin was seen in nodular sclerosing Hodgkin's disease, although heavily hyalinised areas exhibited only superficial positivity. Reed-Sternberg and mononuclear Hodgkin's cells were consistently negative for fibronectin. Laminin staining was localised to vascular and marginal sinus basement membranes. No cellular positivity was evident. The distribution of laminin indicated a pronounced increase in vascularity in nodular sclerosing Hodgkin's disease, which was especially prevalent within the dense fibrous trabeculae. In contrast, however, examination of the other Rye subtypes showed a lesser degree of vascularity with numbers of vessels similar to those observed in reactive follicular hyperplasia. Laminin was found to be more efficient than factor VIII related antigen as a vascular marker.

The forearm bone mineral content of Polynesian and European women in New Zealand was measured to assess whether the inter-racial differences found in other populations also occurred in these two groups. The bone mineral content of the nondominant distal radius and ulna was measured by single photon absorptiometry in 123 European and 80 Polynesian women. The mean values were about 20% higher in Polynesians than in Europeans. The reason for this difference in bone mineral content is unknown but the findings do show that high bone density is not confined to African races and that inter-racial differences in bone mineral content may be more common than has been thought hitherto.

Three cases of T cell lymphoma affecting the marrow, in which initial bone marrow appearances were misleading, occurred. In each case the initial clinical presentation was related to cytopenia, but the marrow abnormalities at this time suggested an abnormal myeloid proliferative state, with no evidence of a malignant lymphoid proliferation. Later in the course of the disease, however, the characteristic pattern of marrow infiltration by mature post-thymic T cells became evident. The consequent delay (two to 36 months) in diagnosis was noted.

An aplastic crisis associated with parvovirus infection occurred in a patient suffering from hereditary erythrocytic multinuclearity associated with a positive acidified (Hams) test (HEMPAS). This case emphasises that any patient who has a shortened red cell survival is susceptible to an aplastic crisis induced by parvovirus.

Absidiosis , diagnosed after biopsy of an anterior cervical mass, is described in a patient who was in remission from acute myeloid leukaemia.

The concentration of fibronectin was assessed in a variety of coagulation factor preparations. Highest concentrations of fibronectin were found in the intermediate purity factor VIII concentrates. Significant amounts were found in cryoprecipitate but high purity factor VIII concentrates contained only small amounts. For practical purposes factor IX concentrates contained no fibronectin. Qualitative estimation of fibronectin showed the presence of an abnormal slow migrating peak on 2 DIEP which was not found in normal plasma. In vivo recovery infused fibronectin was relatively low for all products studied (30-54%). The plasma half life (17-25 h) did not differ significantly depending on whether cryoprecipitate or a factor VIII concentrate was used as a source of fibronectin. No enhancement of plasma fibronectin concentrations was obtained following DDAVP infusion, venous occlusion and exercise. Plasma fibronectin concentrations and 2 DIEP patterns were unaltered following prolonged storage.

The distribution of laminin and collagen type IV in normal human bone marrow appeared to be limited to a small number of capillary and sinusoidal basement membranes. Cellular elements including megakaryocytes showed a negative staining reaction. In contrast, myelofibrotic bone marrow showed markedly increased quantities of both laminin and collagen type IV. This was consistent with a proliferation of endothelial cells within the marrow as confirmed by factor VIII RAG staining. It is suggested that in myelofibrosis in addition to a marked fibrous reaction proliferation of vascular elements is also prominent.

The antihypertensive effects and steady-state pharmacokinetics of doxazosin, as well as the bioequivalence of four dosage forms, were studied in 25 hypertensive patients. For an 8 mg daily dose mean Cmax at steady-state for all patients was 108 ng/ml; the mean tmax was 1.8 h. The mean terminal elimination half-life was 22 h. The four tablets containing 1, 2, 4, or 8 mg of doxazosin were bioequivalent in delivering the 8 mg dose. In patients with mild to moderate hypertension, 26-day treatment with doxazosin resulted in blood pressure reduction of 10/7 mmHg in the supine and 13/18 mmHg in the standing position. Adverse effects were generally mild and of brief duration.

B-chronic lymphocytic leukaemia (B-CLL) patients can be ranked along a progression of phenotypes characterized by a decreasing surface expression of CD20, CD21, CD22 and membrane immunoglobulin and a gradual replacement of the high molecular weight (MW) glycoproteins of the leucocyte-common antigen (LC) CD45RA by the lower MW components, including the CD45RO determinant. As CD20, CD21, CD22 and membrane immunoglobulin change during or after B-cell activation, and the CD45RA/CD45RO inversion is implicated in T-cell maturation, the possibility that the phenotypic differences are generated by a maturational diversity of the CLL clones has been investigated by testing the effects of TPA treatment of the leukaemic cells. TPA reduces the level of expression of CD20, CD21, mIg and CD45RA and increases CD45RO binding, thereby minimizing the phenotypic heterogeneity of the CLL clones and causing them to converge towards one end of the natural range. We propose that the phenotypic diversity in CLL is, at least in part, a consequence of maturational diversity where lymphocyte development is disrupted at different stages in different patients.

Thirty consecutive patients presenting with acute leukaemia were studied throughout their hospital course to determine if plasma-alpha 2 antiplasmin (P-AP) complexes could be detected during episodes of increased fibrinolytic activity and to correlate this finding with other more conventional laboratory parameters. Increased fibrinolytic activity was a common finding, it was detected in 19 (63%) patients. This was usually present at diagnosis, but occasionally occurred later as a transient phenomenon. Increased fibrinolytic activity could not clearly be associated with either infection or chemotherapy. P-AP complexes were found in 11 (37%) patients and were almost always accompanied by additional laboratory evidence of increased fibrinolysis. These complexes were present in most instances at diagnosis and disappeared following successful chemotherapy. Forty-five per cent of patients with P-AP complexes had low alpha 2-antiplasmin levels and 36% had low plasminogen levels which returned to normal following successful chemotherapy. At diagnosis six of eight patients with P-AP complexes had major haemorrhagic manifestations.

The ELT-800 WBC and three-part WBC screen have been evaluated. Technical assessment showed each to be satisfactory but in a small number of samples, the total WBC was found to be incorrect. Discrepancies were found in some cases of chronic lymphatic leukaemia, sickle cell disease and paraproteinaemia. The reasons for these differences are discussed. In the population studied, an accurate WBC screen was obtained on 87.3% of samples. Initial instrument WBC screen rejection occurred on 12.7% but in only 2.1% could no explanation be found to account for this.

Cryostat sections of bone marrow biopsies were stained immuno-enzymatically for fibronectin using the alkaline phosphatase: anti-alkaline phosphatase (APAAP) technique. In normal marrow fibronectin was present only in megakaryocytes and the walls of blood vessels. In contrast, myelofibrotic bone marrow possessed an extensive distribution of fibronectin which did not correspond to the distribution of reticulin. Infiltrated and hypercellular marrows showed an increase in fibronectin which appeared to be related to increased marrow vascularity. Again no correlation with the reticulin pattern was evident. In contrast to platelets, other circulating blood cells had no demonstrable fibronectin. This study suggests that fibronectin does not act as a mediator of haemopoiesis in vivo as has been suggested by the results of experiments in non-human models.

A 51-year-old white man of Irish extraction was found to have apparent 'sporadic' hereditary spherocytosis with a reticulocyte count of 6%. Twelve of his 13 siblings were examined and found to be haematologically normal. The patient's erythrocytes were found to have a diminished amount of spectrin as compared to his siblings and to unrelated controls. It is suggested that the proband may represent either a new mutant or possibly double heterozygosity for two inherited biochemical variants of the red cell membrane skeleton which individually give no haematological abnormalities.

Ketorolac tromethamine, an analgesic agent with prostaglandin synthetase--inhibiting activity, is more active than aspirin in vitro in inhibiting collagen- or arachidonic acid-induced platelet aggregation. In this randomized, double-blind study, 26 volunteers received ketorolac, 30 mg intramuscularly four times a day for 5 days, and placebo, two capsules orally four times a day for at the last 2 study days. The effects of this treatment were compared with those of intramuscular placebo and oral aspirin, two 325 mg capsules, given on the same schedule to eight volunteers. Aspirin at a mean serum concentration of 84 micrograms/ml did not affect prothrombin time, partial thromboplastin time, platelet count, or bleeding time. Ketorolac produced a modest prolongation of the bleeding time, from 4.9 +/- 1.1 minutes (mean +/- SD) to 7.8 +/- 4.0 minutes (p less than 0.005). Ketorolac did not affect the prothrombin time or partial thromboplastin time but was associated with clinically insignificant change in the platelet count from 303 +/- 57 X 10(3)/m3 to 277 +/- 56 X 10(3)/mm3.

The developmental sequence of a neurotropic strain (JHM) of mouse hepatitis virus was examined by transmission electron microscopy and immunocytology. The nucleoprotein core of this coronavirus, which contains RNA of positive polarity and is helical in configuration, becomes incorporated into enveloped particles in the same manner as the nucleocapsids of the orthomyxo- and paramyxoviruses. However, JHM virus is assembled intracellularly by budding at surfaces of smooth membranous vacuoles. A comparison of JHM virus replication in L2 and 17Cl-1 cell lines revealed that L2 cells undergo more rapid cytopathology and cease virus production much sooner than 17Cl-l cells. In L2 cells the accumulation of core material appears to continue after the abrupt cessation of virus assembly. This is evident by the massive cytoplasmic accumulation of structure resembling nucleocapsids, which react with hybridoma antibody to the nucleocapsid antigen as demonstrated by the immunoperoxidase procedure. The current findings are consistent with our previously published demonstration, using cells of neural and other deviation, of the fundamental role of the host cell type in regulating the replication and expression of coronaviruses.

Pairs of bone marrow trephine samples from 67 patients with known or suspected non-Hodgkin's lymphoma (NHL) were collected. One sample was processed for morphological examination, the other for frozen section immunohistology, using a panel of monoclonal antibodies (MAB) reacting with lymphocyte and macrophage determinants, detected by the immuno-alkaline-phosphatase (APAAP) method. Forty-one cases showed definite (36) or suspected (5) involvement of the marrow by NHL. Most were examples of lymphocytic or centroblastic/centrocytic NHL. The pattern of immunostaining confirmed the presence of NHL in these cases: the phenotype of the neoplastic cells was broadly consistent with nodal histology, where available. In ten cases, the marrow showed no evidence of involvement by NHL, and in 15, the eventual diagnosis was an abnormality of the myeloid series. These two groups of marrows not involved by NHL both showed a 'reactive' pattern of immunostaining, comprising polyclonal B-cells, T-helper and suppressor/cytotoxic cells and macrophages. We conclude that immunohistological examination of the bone marrow is useful in cases where the specimen shows morphological evidence of NHL, including those that are only 'suspect', but does not detect lymphoma where there is no morphological evidence of involvement.

Eleven male chronic schizophrenics were given, serially, oral pimozide, fluphenazine, and flupenthixol; the two latter were also given intramuscularly as decanoates in oil. Oral haloperidol was given before and after each drug. Analysis of variance of steady state plasma levels of the different neuroleptics showed considerable within-individual variation in such levels, probably due to differences in absorption and metabolism and between routes of administration. The findings suggest that if a patient fails to respond to one neuroleptic, there may be good pharmacokinetic reasons for switching him to another belonging to a different group, or for giving the same neuroleptic by a different route of administration. The study also showed that previous administration of one neurololeptic may influence the steady state level of another. The various neuroleptics produced different effects on plasma prolactin levels.

Of 34 patients with chronic inflammatory bowel disease (CIBD), 4 developed well-documented episodes of deep-venous thrombosis. All 4 patients had active disease at the time of thrombosis. This group was studied to determine if the tendency to deep-venous thrombosis in patients with CIBD was associated with reduced antithrombin activity by measuring the concentration of three thrombin inhibitors, antithrombin III (AT III), alpha 2-macroglobulin (alpha 2 M) and alpha 1-antitrypsin. 2 patients had low AT III levels and 10 had low alpha 2 M levels. 2 patients who developed deep-venous thrombosis had significantly low levels of both AT III and alpha 2 M. It is suggested that in patients with diseases predisposing to thrombosis and associated with low AT III levels, the measurement of alpha 2 M in addition to AT III may predict those particularly at risk.