Search PubMed⌕ Search

Biomedical subjects

S J Machin

Publications and source records attributed to S J Machin.

At least 163 records · Page 9Linked to original sources
PubMed1988

A severe coagulopathy following volume replacement with hydroxyethyl starch in a Jehovah's Witness.

Blood volume was maintained by an infusion of hydroxyethyl starch 2000 ml (Hespan: HES) during and for the first 28 hours after a major orthopaedic operation in a 13-year-old girl who was a Jehovah's Witness. This was responsible for a generalised clinical haemorrhagic state, an acquired coagulopathy associated with a shortened thrombin, prolonged prothrombin and activated partial thromboplastin times, and an acquired von Willebrand syndrome. The coagulation, after cessation of the infusion of HES, did not become normal until approximately 72 hours later.

Adolescent↗
PubMed1988

The development of hypoprothrombinaemia following antibiotic therapy in malnourished patients with low serum vitamin K1 levels.

A group of nine well-nourished patients, with normal serum vitamin K1 levels (mean 546, range 310-1350 pg/ml), maintained normal prothrombin times (PTs) and factor VII clotting activities throughout a 7 d course of i.v. cefotetan disodium, an N-methyl-thiotetrazole (NMTT) containing cephalosporin antibiotic. However, 11 of 20 patients, with acute intra-abdominal sepsis and initially normal PTs who underwent emergency surgery, developed prolonged PTs (INR 1.4-3.1) associated with reduction in factor VII activities (0.74-0.38 u/ml) after 3-7 d of antibiotic therapy. Nine of these 11 patients had clinical evidence of malnutrition and nine had subnormal serum vitamin K1 levels (mean 119, range 43-354 pg/ml) on admission. Seven received cefotetan but four were treated with a non-NMTT-containing cephalosporin or antibiotics belonging to other groups. The nine patients who maintained normal PTs all had normal nutritional status and normal serum vitamin K1 levels (mean 279, range 103-915 pg/ml) at presentation. The PT is a relatively insensitive indicator of vitamin K stores, and malnourished patients with low serum vitamin K1 levels are at risk of developing hypoprothrombinaemia following intravenous antibiotic therapy.

Adult↗
PubMed1988

A comparison of the effects of two triphasic oral contraceptives on haemostasis.

The effects of two cyclically administered, triphasic, combined low dosage oestrogen and progestogen oral contraceptives on haemostasis have been compared in a longitudinal study, over 6 months, in 26 healthy females aged 16-30 years. Subjects received either Logynon (ethinyl oestradiol and Levonorgestrol, n = 14) or SHD 415G (Schering U.K., n = 12), which contains a similar dosage of ethinyl oestradiol, but in combination with a new progestogen, gestodene. Both groups showed increases in biological activities of procoagulant factors fibrinogen, X and XII and decreased activity of the naturally occurring coagulation inhibitor antithrombin III (AT-III). The majority of these changes were statistically significant (P less than 0.05 to less than 0.001), apparent after one cycle and maintained over the six cycle period. FVII activity increased in both groups, achieving statistical significance (P less than 0.01) by cycle 6 in the SHD 415G group but not in the females receiving Logynon. Protein C activity remained unchanged in both groups. Between-group comparisons showed no differences in the procoagulant factor changes, but protein C was lower (P less than 0.05) in the SHD 415G group after three cycles of therapy. These findings indicate that both triphasic oral contraceptives Logynon and SHD 415G induce increases in procoagulant factor activities which are not balanced by increased biological levels of the two most important physiological coagulation inhibitors AT-III and protein C. These prothrombotic changes are not modified by the new progestogen, gestodene.

Adolescent↗
PubMed1988

The use of the H*1 in predicting marrow recovery following ablative chemotherapy in leukaemia and lymphoma.

Twenty-three cytopenic episodes in 18 patients undergoing ablative chemotherapy for the treatment of leukaemia or lymphoma were monitored from commencement of treatment until recovery, by automated differential counts using the Technicon H*1 Autoanalyser, with particular reference to abnormal white cell flags and large unstained cell (LUC) percentage. The blast flag was indicated in this recovery phase in 100% of patients and in 85% this preceded bone marrow recovery (defined as neutrophil count greater than 0.5 X 10(9)/l) by a mean of 10 days. On average the blast flag was indicated for 8 days in total. Bone marrow function continued to improve in all patients with no evidence of relapse. An increase in the LUC percentage on the differential count reached a maximum at 18 days, 6 days prior to marrow recovery. The ability to detect impending marrow recovery by means of the positive blast flag, may be of great value when patients have been cytopenic for many days.

Autoanalysis↗
PubMed1988

The effect of nicotine on human endothelial cell release of prostaglandins and ultrastructure.

The acute and sub-acute effects of nicotine at concentrations between 10(-9)M and 10(-2)M on human umbilical vein endothelial cell release of prostacyclin and prostaglandin E2 and the sub-acute effect on the endothelial cell ultrastructure have been examined. The acute effect of nicotine on prostaglandin release has been assessed by measuring release of prostacyclin and prostaglandin E2 following stimulation of confluent monolayers of endothelial cells with A23187 in the presence of nicotine. The sub-acute effect has been assessed by measuring A23187 stimulated release of prostacyclin and prostaglandin E2 from endothelial cells grown to confluence in the presence of nicotine. The cell monolayers were also examined for morphological and ultrastructural changes using light and electron microscopy. Nicotine treated and untreated cells released minimal amounts of prostaglandin E2. Concentrations of nicotine between 10(-9)M and 10(-4)M did not inhibit release of prostacyclin or induce morphological changes. Acute exposure to 10(-3)M nicotine resulted in a statistically significant inhibition of prostacyclin release, however, sub-acute exposure did not inhibit prostaglandin release or effect the cell morphology. Acute and sub-acute exposure to 10(-2)M nicotine resulted in a statistically significant inhibition of prostacyclin release. This was accompanied by the appearance of large translucent cytoplasmic inclusions which did not appear to be lipid rich as indicated by the negative uptake of oil-red-O and osmium tetroxide. This study shows that concentrations of nicotine comparable to the plasma levels of smokers (10(-9)-10(-6)M) do not induce morphological changes or effect the release of endothelial prostaglandins.

Calcimycin↗
PubMed1987

The effects of cefotetan disodium on haemostasis.

A 7-day course of intravenous cefotetan disodium was given to nine patients. No significant changes were observed in haematological or biochemical parameters and serum vitamin K1 levels, prothrombin times, factor VII levels, thrombin times and activated partial thromboplastin times remained within the normal ranges throughout the treatment period in all patients. There was no evidence of clinical bleeding in any patient although in two the bleeding time was prolonged up to 13.0 min after 7 days' therapy. Notably, adenosine-5-diphosphate (ADP)-induced platelet aggregation responses were significantly increased (P less than 0.05) at the end of the treatment period. These data indicate that cefotetan disodium at a dose of up to 4 g daily can be used without risk of a bleeding diathesis. In situations associated with vitamin K1 deficiency, potential prolongation of the prothrombin time should be avoided by prophylactic vitamin K1 administration.

Adult↗
PubMed1987

Serum from patients with Raynaud's phenomenon inhibits prostacyclin production.

Prostacyclin (PGI2) and PGE2, the predominant cyclooxygenase products of endothelial cells are potent vasodilators. An inability to produce appropriate concentrations of these prostanoids may be a factor in the pathogenesis of the digital vasospasm experienced by patients with Raynaud's phenomenon (RP). The effect of sera from normal subjects, patients with primary RP, and patients with RP in association with systemic sclerosis (SS) on the production of PGI2 and PGE2 by cultured human endothelial cells was investigated. All sera produced a dose-dependent inhibition of 6-keto-PGF1 alpha, but both the 10% and 20% sera from patients with RP and SS produced a significantly greater inhibition than control sera. The mean production of 6-keto-PGF1 alpha expressed in ng/10(4) cells was 2.278 (normal), 1.9311 (RP), and 2.1824 (SS) after incubation with 1% serum for 24 h. This decreased to 1.3647, 0.5927, and 0.4171, respectively following incubation with 20% sera for 24 h. This represented a 44% (normal), 76% (RP), and 83% (SS) inhibition of 6-keto-PGF1 alpha production compared with serum free media. Similar results were obtained after 1 h incubation experiments. There was a nonsignificant decrease in mean PGE2 production following similar incubations with 1% and 20% sera for 24 h. These results suggest that factor(s) present in the sera of patients with RP may reduce the ability of endothelial cells to synthesize or release the vasodilator and antiaggregatory prostanoid PGI2.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Reduced risk of non-A, non-B hepatitis after a first exposure to 'wet heated' factor VIII concentrate.

The risk of post-infusion non-A, non-B hepatitis (NANBH) in patients receiving a first exposure to unheated or conventionally 'dry heated' factor VIII concentrates approaches 100%, implying invariable contamination of these products. Amongst 18 patients who received a first treatment with a 'wet heated' commercial concentrate, five (28%) developed asymptomatic NANBH, suggesting a more efficient inactivation of NANB agent(s) by this process. 2/9 (22%) of the batches of concentrate used in the study were implicated in NANBH transmission. One of those two batches, responsible for NANBH in four patients, had been prepared from a plasma pool containing an unusually large proportion of donations with high alanine aminotransferase (ALT) levels. A resulting high level of viral contamination in this batch may have been sufficient to override the effects of the sterilization process. All patients remained anti-HIV seronegative at 17-28 months of follow-up.

Adolescent↗
PubMed1987

Familial lupus anticoagulants.

Three families having more than one affected member with SLE or lupus-like disease were investigated by global coagulation tests as well as methods based on dilute thromboplastin, Russell's viper venom and thermal stability/absorption, and by RIA for anticardiolipin (CL) antibodies. Of the 19 persons, 11 had SLE or lupus-like disease. Eight of these 11 had a prolonged KPTT and other evidence of LA, while only 5/11 had high anticardiolipin titres. Four healthy spouses of affected females, and three asymptomatic siblings also had prolonged non-correctable KPTTs. These persons had no bleeding or thrombotic history and normal clotting factor levels. Further clotting tests were negative, although one had raised anti-CL antibody. Such cases may account for some of the patients one finds during routine haemostatic screening with unexplained prolonged KPTT. Although anticardiolipin levels are raised in subjects with LA, there was no close correlation between length of KPTT and anticardiolipin titre. These findings would support a hypothesis of transmissible agents or other environmental factors being involved in lupus-like disorders.

Antibodies↗
PubMed1987

Interactions between prostacyclin analogue ZK 36374 and heparin in their effects upon platelet function.

Prostacyclin and heparin can be administered to patients concurrently, with the aim of maximizing anticoagulant effect. It has been suggested that the two agents may interact in their effects upon platelet function. We have therefore studied this parameter in the presence of ZK 36374, a chemically stable analogue of prostacyclin and heparin, alone and in combination. Platelet responses to ADP and thrombin have been studied by standard aggregometry, and intra-platelet calcium mobilization has simultaneously been recorded after loading the cells with the fluorescent calcium indicator, Quin 2. ZK 36374 alone consistently inhibited platelet aggregation and calcium mobilization in response to ADP and thrombin, in a dose-dependent fashion. Heparin alone did not significantly alter the responses to ADP but consistently reduced those to thrombin. Pre-mixture of ZK36374, with heparin, was shown to interfere with the ability of the prostacyclin analogue to inhibit platelet aggregation and calcium flux in response to ADP. In contrast, ZK 36374 inhibition of platelet responses was markedly enhanced when thrombin was the agonist.

Adenosine Diphosphate↗
PubMed1987

Pyrimethamine in the myeloproliferative disorders: a forgotten treatment?

Eight patients with myeloproliferative disorders, five with polycythaemia rubra vera (PRV) and three with essential thrombocythaemia (ET), have been treated with the anti-folate drug Pyrimethamine for periods ranging from 1 to 24 years. In PRV this treatment was comparable in efficacy to that achieved with Busulphan or radioactive phosphorus, but required more frequent supervision. One patient was controlled on Pyrimethamine, having failed on conventional treatment. The major side effect was thrombocytopenia which was rapidly reversible on stopping the drug. In ET, Pyrimethamine produced satisfactory control of the platelet count and thrombocytopenia did not arise. No neurological sequelae were encountered. One patient developed a non-Hodgkin's lymphoma of the gut, but there were no other cases of secondary malignancy. Pyrimethamine may still have a role in the treatment of selected cases of myeloproliferative disorders.

Adult↗
PubMed1986

Very high dose chemotherapy with autologous bone marrow rescue in adult patients with resistant relapsed lymphoma.

Seventeen patients with advanced lymphoma were treated with high-dose chemotherapy with autologous bone marrow rescue. In 11 patients with non-Hodgkin's lymphoma (NHL) there were 2 complete remissions (CRs) and 2 partial remissions (PRs), and in 6 patients with Hodgkin's disease there were 5 CRs. Three patients remain well in unmaintained remission (days 874, 446 and 351), and a further 2 are alive and still receiving treatment (days 650 and 558). This type of therapy appears useful and should now be considered earlier in the course of the disease.

Adult↗
PubMed1986

Effects of various doses of latamoxef (moxalactam) on haemostasis.

The effects of intravenous latamoxef therapy at two doses of 3g and 6g daily for 7 days was assessed by various haemostatic parameters. With both doses, the prothrombin time, thrombin time and activated partial thromboplastin time remained within the normal range throughout the study. However, with the 6g day-1 dose there was a marked prolongation of the bleeding time associated with defective platelet aggregation to adenosine diphosphate and low dose collagen after 7 days therapy. With the 3g day-1 dose of latamoxef, there was no prolongation of the bleeding time and only minor changes in platelet aggregation responses.

Bleeding Time↗
PubMed1986

Contrast, coagulation, and fibrinolysis.

Some adverse clinical effects of intravascular radiologic contrast agents have been attributed to their interference with the normal hemostatic processes. This study compares the effects of the low osmolality agents with those of the conventional agents by in vitro studies of platelet function, fibrin formation, and fibrinolytic activation. In various degrees, all the contrast agents studied inhibit platelet aggregation and fibrin formation but show virtually no direct activation of fibrinolysis. The new low osmolality agents generally show lesser inhibitory effects on the hemostatic mechanisms. Some clinical implications are discussed.

Blood Coagulation↗