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K J Walshe

Publications and source records attributed to K J Walshe.

4 recordsLinked to original sources
PubMed1990

Heparin cofactor II levels are increased by the use of combined oral contraceptives.

Heparin cofactor II (HCII) was assayed by a microtitre amidolytic substrate technique. A linear response was obtained up to 1.5 U/ml and HCII levels were not affected by freezing and thawing the plasma. The assay was validated by comparing HCII and antithrombin III (AT III) levels in AT-III-deficient plasmas and samples from critically ill patients. Higher HCII levels were found in healthy normal women than in healthy normal men (means 1.16 and 0.97 U/ml, respectively, P less than 0.01). A significant increase in HCII levels from 0.86 to 1.10 U/ml (mean values) was seen in healthy normal women starting on combined oral contraceptive (COC) preparations (P less than 0.001). Increased HCII levels were maintained over a 6-month period, but fell towards normal 14 days after stopping COC, although they were still significantly higher than before starting COCs. The discrepancy in HCII level between normal men and women may be due to COC use. In clinical studies, different reference ranges should be used for men and women, and the need for careful questioning about the use of COCs is emphasized.

Adolescent↗
PubMed1989

Plasma from patients with severe Lassa fever profoundly modulates f-met-leu-phe induced superoxide generation in neutrophils.

A recurrent theme in studies of the pathology of fatal Lassa fever in man is the lack of histological lesions to explain disordered cell function and death. Recently, we demonstrated the existence of a factor in the plasma of patients with Lassa fever which markedly inhibits the aggregation responses of normal platelets in vitro. To assess whether this factor could mediate more global cellular dysfunction, we studied the effects of Lassa plasma on the respiratory burst of neutrophils. Thirteen of 15 samples from patients in the acute phase of Lassa fever profoundly inhibited the amount of superoxide generated by normal neutrophils in response to the chemotactic peptide, f-met-leu-phe (FMLP) (mean superoxide generated = 54.7 +/- 6.1% of control). In contrast, eight of nine samples from patients who had infections other than Lassa fever enhanced the neutrophil response to the peptide. All Lassa samples which inhibited the ADP-induced aggregation responses of normal platelets inhibited the neutrophil response to FMLP. Unlike the effect on platelets, however, the inhibition of neutrophils was only apparent when the cells were stimulated within 5 min of exposure to the plasma. The inhibition of neutrophils is not due to either interference with FMLP-neutrophil binding or an effect on the NADPH-oxidase, suggesting a suppression of signal transduction. Our data suggest the inhibitory factor in Lassa plasma has global effects on cellular function, and may play a central role in the pathogenesis of this often fatal illness.

Acute Disease↗
PubMed1989

A plasma inhibitor of platelet aggregation in patients with Lassa fever.

Previous studies have shown that haemorrhage in Lassa fever is associated with abnormal in vitro platelet aggregation and a high mortality. In Sierra Leone we studied platelet aggregation in healthy local subjects, patients with laboratory-confirmed Lassa fever and febrile patients in whom Lassa virus infection was excluded. There were no significant differences in the mean platelet counts of these groups. Patients with fulminant Lassa virus infection showed a gross depression of in-vitro platelet responsiveness to 1 and 5 microM ADP and 4 micrograms/ml collagen compared to other groups (P = 0.0004-0.0008 when compared to healthy controls, P = 0.002-0.0008 when compared to mild Lassa fever patients). When plasma samples from five of these patients were mixed 1:1 with control platelet-rich plasma, a marked inhibition of ADP-induced aggregation was observed. No inhibitory activity was detected in plasma obtained from healthy subjects or febrile control patients. The presence of inhibitor was strongly associated with the occurrence of haemorrhage (P = 0.03), depression of platelet aggregation (P = 0.004) and severity of Lassa fever (P = 0.007).

Adenosine Diphosphate↗