Heparin-induced thrombocytopenia and the use of r-hirudin during cardiopulmonary bypass.

We report the successful use of r-hirudin (lepirudin) for cardiopulmonary bypass in a 67-year-old man who developed heparin-induced thrombocytopenia type II during heparin treatment of an extensive deep venous thrombosis. Lepirudin was monitored by the modified ecarin clotting time in a "mobile laboratory" set up next to the cardiac theatre, aiming for lepirudin levels of 3.5 to 4.5 microg/ml during bypass.

Effects of combined oral hormone replacement therapy on tissue factor pathway inhibitor and factor VII.

Oral combined hormone replacement therapy (HRT) with oestradiol and norethisterone increases plasma levels of prothrombin fragment 1+2 (F1+2), indicating an increase in thrombin generation, but the mechanisms underlying this increase are uncertain. The aim of this randomized, placebo-controlled study was to determine whether an increase in factor VII, a factor that combines with tissue factor to activate the extrinsic pathway, or a decrease in tissue factor pathway inhibitor (TFPI), an inhibitor of extrinsic pathway activation, may contribute to increases in thrombin generation occurring with HRT. Healthy postmenopausal women aged 50-75 years received placebo (n=19) or oral combined HRT (n=18) and had blood collected for measurement of factor VII coagulation activity (VIIc), activated factor VII (VIIa) and TFPI at baseline and at 6 weeks. Baseline characteristics were similar in the two groups, including age, body mass index and cholesterol levels. As reported previously, HRT increased the F1+2 concentration by 20%. Placebo had no effect on VIIc, VIIa or TFPI, but 6 weeks of combined HRT decreased VIIc [from 1.11+/-0.06 (mean+/-S.E.M.) to 1.03+/-0.06 i.u./ml; P<0.03], VIIa [from 43.9; 10.8-198.3 (median; range) to 35.0; 6.3-66.8 m-units/ml; P<0.03] and TFPI [from 81.3+/-6.5 to 60.4+/-5.5 ng/ml; P<0.0001]. The decrease in TPFI with HRT was not correlated with the elevation in F1+2 levels. In conclusion, the increase in thrombin generation seen with HRT is not due to an effect on factor VII; in addition, while a contribution from the decrease in TFPI is possible, increased thrombin generation is not directly related to the decrease in TFPI.

Structure and stereochemistry of triflavanoids containing both ether and carbon-carbon interflavanyl bonds.

The first triflavanoids with both C-C and C-O-C interflavanyl bonds, epioritin-(4beta-->6)-epioritin-(4alpha-->4)-epioritin-4beta-ol, epioritin-(4beta-->3)-epioritin-(4beta-->6)-epioritin-4beta-ol and epioritin-(4beta-->3)-epioritin-(4beta-->6)-epimesquitol-4alpha-ol, were identified in the heartwood of Acacia caffra. The ethereal interflavanyl bond is readily susceptible to reductive cleavage with sodium cyanoborohydride in trifluoroacetic acid/dichloromethane which hence permits the unequivocal assignment of the absolute configuration of constituent flavanyl units.

Postmenopausal hormone replacement therapy increases coagulation activity and fibrinolysis.

Hormone replacement therapy (HRT) appears to be cardioprotective in postmenopausal women; however, concerns exist over its thrombogenic effects. To address the effects of combined HRT on coagulation and fibrinolysis, we have measured circulating markers of these processes in a double-blind placebo-controlled trial. Forty-two healthy postmenopausal women aged 50 to 75 years received continuous combined HRT with 2 mg estradiol+1 mg norethisterone or placebo for 6 weeks. Hormone profiles were measured at baseline, and lipid and hemostatic parameters were measured at baseline and after 6 weeks of therapy. Baseline characteristics were similar in the 2 groups. With change from baseline the main outcome measure, HRT increased the markers of coagulation (prothrombin fragments 1+2, 0.20+/-0.06 versus 0.06+/-0.04 nmol/L, P=0.0005; soluble fibrin, 2.3+/-0.4 versus 0.25+/-0.3 microgram/mL, P=0.0004), reduced plasma fibrinolytic inhibitory activity (plasminogen activator inhibitor-1, -0.67+/-0.16 versus 0.24+/-0.21 U/mL, P=0.002), and increased fibrinolysis (D-dimer, 24+/-12 versus -6+/-8 ng/mL, P=0.04) compared with placebo. Increases in soluble fibrin and D-dimer were positively correlated (r=0.59, P=0.02), but changes in plasminogen activator inhibitor-1 and D-dimer were unrelated. Although baseline hemostatic and lipid parameters were correlated, there were no associations between changes in hemostatic markers and lipids after treatment. Short-term oral combined continuous HRT (estradiol and norethisterone) increased thrombin and fibrin generation, reduced plasma fibrinolytic inhibitory activity, and increased fibrinolysis. Enhanced fibrinolysis was related to increased fibrin generation but not reduced plasma fibrinolytic inhibitory activity. Coagulation activation may partly explain the increases in venous thrombosis and cardiovascular events reported with the use of combined HRT.

Structure and synthesis of the first procassinidin dimers based on epicatechin, and gallo- and epigallo-catechin.

The range of natural dimeric procassinidins is extended by identification of cassiaflavan-(4alpha-->8)-epicatechin, cassiaflavan-(4alpha 8)-epigallocatechin, cassiaflavan-(4beta-->8)-epicatechin, cassiaflavan-(4beta-->8)-epigallocatechin, cassiaflavan-(4beta-->8)-gallocatechin, ent-cassiaflavan-(4beta-->8)-epicatechin and cassiaflavan-(4alpha-->6)-epicatechin in the bark of Cassia petersiana. Their structures and absolute configuration were confirmed by synthesis.

Structure and synthesis of ether-linked proteracacinidin and promelacacinidin proanthocyanidins from Acacia caffra.

Two new ether-linked proanthocyanidins, epioritin-(4beta-->3)-epioritin-4beta-ol and epimesquitol-(4beta-->4)-epioritin-4beta-ol, were isolated from the heartwood of Acacia caffra. Their structures and absolute configurations were established by spectroscopic methods and syntheses.

Tyrosinase catalysed biphenyl construction from flavan-3-ol substrates.

Mushroom tyrosinase catalysed oxidation of three flavan-3-ols, viz. catechin, fisetinidol and mesquitol, was conducted to construct biphenyl bonds. Exposure of the flavan-3-ols to tyrosinase and subsequent trapping of the o-quinone intermediates resulted in the formation of novel flavan-3-ol derivatives, the structures of which were elucidated by mono- and two-dimensional 1H-NMR experiments. Application of the methodology resulted in the improved synthesis of the natural flavan-3-ol dimer, mesquitol-[5-->8]-catechin, previously isolated from Prosopis glandulosa.

[Guidelines for professional responsibilities of the head nurse in South African state hospitals]. / Riglyne vir die hoofverpleegkundige se posverantwoordelikhede in Suid-Afrikaanse staatshospitale.

This is a follow-up article on a functional analysis of the post responsibilities of the Chief Professional Nurse in South African State hospitals. The purpose of this study is to formulate guidelines for the Chief Professional Nurse's post responsibilities in State hospitals. The final statements, on which the conceptual framework is based, are inferred from the previous justified objectives: the exploration and description of the existing job/post descriptions of the Chief Professional Nurse, an exploration and description of the different role-players' expectations regarding the post/job responsibilities of the Chief Professional Nurse, followed by a literature control. The guidelines are formulated and it is recommended that they be implemented, followed by the testing of various hypotheses to confirm the value of these guidelines.

[Function analysis of the job responsibilities of head nurses]. / 'n Funksieverrekening van die hoofverpleegkundige se posverantwoordelikhede.

There are many internal and external factors impacting on the utilisation of the Chief Professional Nurse in South African State hospitals. The aim with this research is to undertake a functional analysis of the post responsibilities of the Chief Professional Nurse in South African State hospitals. This objective is justified by means of an exploratory, descriptive and qualitative research strategy. The existing job descriptions of the Chief Professional Nurse are explored and described, followed by an analysis of the expectations of various role-players (the Senior Nursing Service Manager, Chief Professional Nurse, Senior Registered Nurse, as well as the provincial policy makers in health care) regarding the post responsibilities of the Chief Professional Nurse. A content analysis of existing job descriptions is performed, followed by focus group interviews with the Nursing Service Managers and Chief Professional Nurses, work shops with the Senior Registered Nurses, and written inputs by the provincial policy makers in health care services. The results reveal misutilization of the Chief Professional Nurse in South African State hospitals. The expectations of the different role players focus on the traditional generic functions of the Chief Professional Nurse, viz. patient care, administration, education and research. New insights are added to ensure that the Chief Professional Nurse is utilised as a clinical nurse specialist.

[Sequela of hand burns in children: 32 cases followed and treated in the Plastic Surgery and Reconstruction department of the University Hospital Center of Treichville, Abidjan]. / Les sequelles de brûlures de la main chez l'enfant: a propos de 32 cas suivis et traités à la Consultation de Chirurgie Plastique et Reconstructrice du Centre Hospitalier Universitaire de Treichville-Abidjan.

An investigation on the effects of hand burns has been undertaken about 32 children admitted in the plastic surgery outpatients Department. Accident occurs among the lower class population and heat is the major factor pointed out. The most frequent effects are hand palmar contracture. The surgical treatment completed with the functional re-education has given very good results in 79% cases. However the cheloid contractures are the most difficult to cure. Indeed the authors insist or the prevention and the creation of a center of burned patients and a plastic surgery Service to take care of patients whose life prognostic is optimistic.

IgG subclass values from normal children in Cape Town.

Sensitive and reproducible enzyme-linked immunoabsorbent assays (ELISA) have been developed to quantitate IgG subclass levels using monoclonal antibodies. Normal values for serum IgG subclass levels were determined in 300 healthy children between 6 months and 14 years of age and in 80 adults. High levels of IgG1 and delayed maturational development of IgG2 in children from Cape Town are different to results reported from developed countries. Genetic differences may account for this.

[Dupuytren's contracture: review of the literature. Case report of a black African]. / La maladie de Dupuytren: revue de la litterature. A propos d'un cas chez l'Africain noir.

In one case of Dupuytren's contracture the authors make an important literature review. The affection is rare with the black man but frequent in caucasian population. Its origin is therefore european. They point out alcoholism and microtrauma due to the patient's antecedents and job.

[Intra-keloid excision and deferred corticoid infiltration in the treatment of keloids. University Hospital Center of Treichville-Abidjan]. / Exérèse intra-chéloïdienne et infiltration différée de corticoïdes dans le traitement des chéloïdes. (Centre Hospitalier Universitaire de Treichville-Abidjan).

On a series of 38 keloid surgery patients the authors noted a strong female predominance and the frequency of ear lobule keloid. After some rather unsuccessful excision-suture of the keloid they recommend the intra- keloid excision to be followed by a late corticoid infiltration but deferred until the 15th day. The results obtained were encouraging but some researches have to be made with regard to the etiology of this affection which might probably resolve the therapeutic problem.

Platelet antibody levels do not correlate with response to therapy in idiopathic thrombocytopenic purpura.

Platelet bound antibody was measured at presentation in 67 patients with idiopathic thrombocytopenic purpura by means of a quantitative antiglobulin consumption technique. The amounts of antibody present on the platelets of patients who failed steroid therapy were similar to those present on the platelets of patients who achieved a remission of their illness. It was also not possible on the basis of these data to identify those patients whose illness would remit after splenectomy. It is concluded that the pretreatment platelet antibody level does not assist in predicting the responses to treatment.

Complement (C3) binding to platelets in autoimmune thrombocytopenia.

In view of conflicting reports on the occurrence of complement binding to platelets in idiopathic autoimmune thrombocytopenic purpura (AITP) we performed measurements of platelet bound C3 in patients with AITP who had elevated levels of platelet bound IgG. Using a quantitative antiglobulin consumption technique 38 out of 42 patients were found to have fixed abnormally large amounts of C3 to their platelets, and a significant positive correlation between the amounts of platelet bound IgG and C3 was shown to exist. In additional experiments antibody eluates were prepared from AITP platelets and were shown to cause the fixation of C3 to normal donor platelets in vitro. Taken together these findings strongly suggest that the C3 binding in AITP is specifically related to the disease process.

Platelet-bound IgG measurements in idiopathic thrombocytopenic purpura.

A quantitative antiglobulin consumption technique has been used to measure antiplatelet antibody (platelet-bound IgG) in 25 patients with idiopathic thrombocytopenic purpura (ITP). The assay confirmed the presumptive clinical diagnosis in all patients. Additional observations however, have demonstrated that if thrombocytopenic patients have platelet counts greater than 75 x 10(9)l, false-negative results may be obtained. Antiplatelet antibody levels closely mirrored the clinical progress of patients receiving therapy, but the level of antibody at the time of diagnosis was not of value in predicting the response to corticosteroid treatment. In a proportion of patients receiving corticosteroids, platelet counts returned to normal before antibody levels, implying a reduction in the sequestration of antibody-sensitized platelets within the reticulo-endothelial system. Because this response was observed in proportionately more patients in whom drug therapy was successful than others, this steroid effect may in some patients be an important factor in determining the successful outcome of medical treatment. Four out of 10 patients in clinical remission had evidence of disease activity based on platelet antibody and platelet survival measurements. The pattern of results obtained demonstrates that disease activity may go unrecognized in some patients unless both measurements are performed.

Effects of the sulphonylurea drugs gliclazide and glibenclamide on blood glucose control and platelet function.

Platelet aggregation and adhesion are commonly increased in diabetes mellitus. These abnormalities may in part be responsible for the increased incidence of vascular disease in diabetics. We have investigated the effects of diet, diet plus glibenclamide, and diet plus gliclazide on plasma glucose control and platelet function in 10 newly diagnosed maturity-onset diabetics who had not previously been treated. Before treatment, the mean postprandial plasma glucose value was 13,4 +/- 0,8 mmol/l, which fell insignificantly on dietary treatment, to 12,2 +/- 1,0 mmol/l (P greater than 0,05). Both glibenclamide and gliclazide, when added to the diet, significantly lowered mean plasma glucose values to 9,3 +/- 0,8 mmol/l and 7,8 +/- 0,8 mmol/l respectively (P less than 0,05). Platelet aggregation in response to 1 mumol adenosine diphosphate (ADP) was increased in the diet period, whereas aggregation in response to 10 mumol and 100 mumol was normal. This suggests an increased sensitivity of the platelets to ADP in diabetic patients. The addition of both glibenclamide and gliclazide reduced the magnitude of the response to within the normal range. Platelet aggregation in response to 10 mumol adrenaline and 750 micrograms/ml collagen was significantly reduced by glibenclamide (P less than 0,05). We conclude that sulphonylurea therapy appears to reduce the increased platelet aggregation which occurs in diabetics. This may play a role in the prevention of vascular disease.

Kinetics of insulin secretion following glucose infusion in patients with atherosclerotic peripheral vascular disease.

Kinetics of insulin secretion following an i.v. glucose infusion, according to the protocol described by Cerasi and Luft, were studied in 19 patients with angiographically documented atherosclerotic peripheral vascular disease and in a group of appropriate controls without clinical signs of disease. No significant differences were noted between patients and controls in plasma cholesterol levels and in the K value following a standard i.v. glucose tolerance test. Blood glucose levels were significantly lower in the patients, whereas mean plasma insulin and triglyceride levels were significantly higher. Analysis of the glucose and insulin responses to the glucose infusion test indicated that 31.6% of the patients had a delayed and sluggish insulin response to the glucose load, fitting the criteria suggested for the diagnosis of prediabetes, versus 10% of the appropriate controls. In particular, simulation of the plasma insulin responses by a square-wave glucose stimulus, confirmed that in a significantly higher number of patients the early insulin peak was below normal limits. The results of this study suggest that increased insulin secretion is not present in patients with atherosclerotic vascular disease, in contrast to reports by other authors, and that inefficient insulin secretory mechanisms may be observed in these patients, thus possibly contributing to the development of the atherosclerotic disease.