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Biomedical subjects

M A Crowther

Publications and source records attributed to M A Crowther.

At least 37 records · Page 2Linked to original sources
PubMed1998

Relation of factor V Leiden genotype to risk for acute deep venous thrombosis after joint replacement surgery.

BACKGROUND: A point mutation in coagulation factor V (A1691G) is associated with increased risk for venous thrombosis. However, limited information is available about the prospective risk for deep venous thrombosis in specific high-risk clinical settings. OBJECTIVE: To determine whether the factor V Leiden mutation is associated with an increased occurrence of deep venous thrombosis in patients undergoing hip or knee replacement surgery. DESIGN: Retrospective analysis of plasma samples obtained during six prospective clinical trials that compared different antithrombotic prophylaxis regimens in patients undergoing hip or knee replacement surgery. SETTING: Inpatients at the University of Rochester Medical Center, McMaster University Medical Center, Hamilton Civic Hospitals, and the Genesee Hospital. PATIENTS: 825 patients hospitalized for hip or knee replacement surgery. MEASUREMENTS: Venographically diagnosed postoperative deep venous thrombosis was correlated with factor V genotype. RESULTS: The factor V Leiden mutation was not associated with a significantly increased risk for venographically detected deep venous thrombosis. The absolute incidence of deep venous thrombosis was 31% (95% CI, 15% to 47%) in patients with the mutation and 26% (CI, 22% to 29%) in patients without the mutation (relative risk, 1.2 [CI, 0.6 to 2.9]). The factor V Leiden mutation was not significantly associated with deep venous thrombosis in subgroups of patients receiving warfarin or heparin. The incidence of clinical hemorrhage was similar in patients with (10%) and without (8%) the mutation. CONCLUSIONS: The factor V Leiden mutation is not a significant risk factor for acute deep venous thrombosis in this group of patients. Current data do not justify routine preoperative screening for this mutation or intensified perioperative prophylaxis in patients with the factor V Leiden mutation who are undergoing hip or knee joint replacement surgery and are receiving effective antithrombotic prophylaxis.

Aged↗
PubMed1998

Low-dose oral vitamin K reliably reverses over-anticoagulation due to warfarin.

BACKGROUND: Patients receiving long-term warfarin frequently develop asymptomatic excessive prolongation of their international normalized ratio (INR) results. The most appropriate management strategy in these patients is unknown. This prospective cohort study was designed to address whether 1 mg of oral vitamin K effectively reduces the INR value of such patients. METHODS: A prospective cohort study was performed in two tertiary care teaching hospitals, in which 62 patients receiving warfarin who had INR values between 4.5 and 10.0 received 1 mg of oral vitamin K. All patients had daily INR values and clinical assessments performed. RESULTS: The mean INR value at presentation was 5.79 (95% confidence interval (CI) 5.48 to 6.09, range 4.5 to 9.5). Sixteen hours after receiving the 1 mg of oral vitamin K, the mean INR was 2.86 (95% CI 2.50 to 3.23). On the second and third days after vitamin K, the mean INR values were 2.20 (1.93 to 2.47) and 2.14 (1.85 to 2.44), respectively. No adverse events or bleeding complications were observed. In three patients (6%) the INR value rose between the time of vitamin K administration and the next INR determination; two patients received a further 2 mg dose of subcutaneous vitamin K. CONCLUSIONS: In patients receiving warfarin who have asymptomatic excessive prolongations in their INR results, 1 mg of oral vitamin K reliably reduces the INR to the therapeutic range within 24 h. This therapy is more convenient, less expensive, and might be safer than parenteral vitamin K. Thus, it should be considered in all non-bleeding patients receiving warfarin, who present with INR results of 4.5 to 9.5.

Administration, Oral↗
PubMed1996

Splenectomy done during hematologic remission to prevent relapse in patients with thrombotic thrombocytopenic purpura.

OBJECTIVE: To assess whether splenectomy done during hematologic remission reduces the relapse rate in patients with relapsing thrombotic thrombocytopenic purpura. DESIGN: Consecutive case series. SETTING: Tertiary care teaching hospital. PATIENTS: 6 consecutive patients seen during a 10-year period who had had one or more relapses of thrombotic thrombocytopenic purpura. INTERVENTIONS: All patients had elective splenectomy while in hematologic remission and were followed after surgery for as long as 8.0 years. MEASUREMENTS: Attack rates (events per year) were calculated for each patient from time of presentation to time of splenectomy and from time of splenectomy to January 1996. RESULTS: A total of 26 episodes of thrombotic thrombocytopenic purpura occurred over 22.3 patient-years before splenectomy. After splenectomy, 3 acute episodes occurred over 22.7 patient-years. The attack rate (+/-1 SD) decreased from 2.3 +/- 2.0 events per year to 0.1 +/- 0.1 events per year. CONCLUSION: In patients who have had one or more relapses of thrombotic thrombocytopenic purpura, splenectomy done during hematologic remission reduces the frequency of acute relapse and the resulting need for medical therapy.

Humans↗
PubMed1996

Thrombocytopenia in pregnancy: diagnosis, pathogenesis and management.

Maternal thrombocytopenia is a common find during pregnancy. The rapid determination of its cause can often be difficult, with the diagnosis only being made in retrospect once the course of the platelet count is known. The majority of patients with thrombocytopenia in pregnancy will have incidental thrombocytopenia of pregnancy which is of no clinical significance.

Female↗
PubMed1996

The evaluation of various mathematical RBC indices and their efficacy in discriminating between thalassemic and non-thalassemic microcytosis.

The differentiation between thalassemic and non-thalassemic microcytosis has important clinical implications in hematology and medicine. A simplified index, based on red cell parameters derived from automated blood cell analyzers, which could be used to discriminate between microcytic patients with a high probability of thalassemia minor and those with a low probability, would be an extremely useful tool. Five mathematical indices have been proposed as useful for this purpose. These are the: Bessman index, Shine and Lal index, England index, Mentzler index, and mean cell volume (MCV) alone. This study was designed to prospectively evaluate the efficacy of these indices. Patient samples were chosen every fourth day from all patient samples referred to the hematology laboratory at St. Joseph's Hospital over a 6-month period. All patient samples with an MCV < 80 fL and age > or = 18 years were considered eligible for the study. After enrollment and laboratory analysis were complete sensitivities and specificities were calculated for each of the indices using a variety of cut-off values and receiver operator characteristic (ROC) curves were constructed. Based on statistical analysis of the area under these curves, the authors conclude that MCV alone is as effective as the Mentzler and Shine and Lal indices in selecting microcytic patient samples with a high probability of thalassemia minor for thalassemia testing. They also conclude that the Bessman index and the England index are ineffective indices for this purpose.

Adult↗
PubMed1996

Free protein S deficiency may be found in patients with antiphospholipid antibodies who do not have systemic lupus erythematosus.

In order to determine if there is a relationship between antiphospholipid antibodies and reduced free protein S levels, we evaluated 21 patients who had an antiphospholipid antibody but had neither a history of venous thromboembolism nor systemic lupus erythematosus (cases) and 55 matched controls, who did not have an antiphospholipid antibody, a history of thrombosis or systemic lupus erythematosus. Cases and controls had similar protein C and antithrombin levels. Six of 21 cases had reduced free protein S antigen levels, compared to 5 of 55 controls (chi 2 = 5.823 p < 0.025). In addition, the mean free protein S level was significantly lower in cases than in controls (0.30 +/- 0.09 units vs 0.39 +/- 0.13 units, p < 0.01, two-tailed Student's t-test). We conclude that antiphospholipid antibodies are associated with a significant decrease in free protein S levels, and that this acquired free protein S deficiency may contribute to the thrombotic diathesis seen in patients with antiphospholipid antibodies.

Adult↗
PubMed1994

Validation of a single point flow cytometric assay for determining P-glycoprotein activity in multidrug resistant cell lines.

P-glycoprotein, a transmembrane protein which acts as an energy dependent efflux pump, has been implicated as one mechanism of multidrug resistance (MDR) in human tumours. Commonly employed assays measure P-glycoprotein immunohistochemically or mdr1 messenger RNA. In this study we compared a single point flow cytometric assay for determining activity of P-glycoprotein with cellular expression of P-glycoprotein determined by Western blot. Five cell lines, with varying levels of multiple drug resistance, were incubated with daunorubicin (DNR) in the presence (treated) and absence (control) of cyclosporine or verapamil, agents known to inhibit the activity of P-glycoprotein. The treated cell lines, along with non-treated controls were examined for intracellular concentrations of DNR measured by fluorescence intensity using a flow cytometer. The ratio of fluorescence intensity expressed in the treated/control was used as an index of functional activity of P-glycoprotein. Functional activity of the P-glycoprotein as determined by flow cytometry correlates highly with cellular content of P-glycoprotein measured by western blot (correlation coefficients of r = 0.90-0.98 for the various cell line combinations). This method represents a rapid single point flow cytometric assay which may be suitable for screening clinical samples for P-glycoprotein activity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Menstrual toxic shock syndrome complicated by persistent bacteremia: case report and review.

An unusual case of menstrual toxic shock syndrome (TSS) is described in which the patient had persistent Staphylococcus aureus bacteremia despite therapy with iv cloxacillin. There was no demonstrable evidence of endocarditis or an abscess as a focus for persisting bacteremia. The strain of S. aureus isolated from the blood and vagina produced toxic shock syndrome toxin 1 (TSST-1) and enterotoxin A. Bacteremia occurs uncommonly in association with TSS; however, aggressive high-dose antistaphylococcal therapy should be instituted for treating this possible complication.

Adult↗
PubMed1991

Vascular collagen fibril morphology in type IV Ehlers-Danlos syndrome.

Morphometric analysis of transmission electron micrographs of blood vessel, skin and dura mater collagen fibers were performed on postmortem tissues taken from 28-year-old female with Ehlers-Danlos type IV syndrome (EDS IV). Vascular tissue from this patient was compared to 5 age- and sex-matched controls (age range 26-28 years). Our study revealed significant variation in collagen fibril diameter in the walls of almost all the vessels studied. In general, the EDS IV tissue showed a net decrease in average collagen fibril cross sectional area in arterial wall samples. This decrease was significant (p less than .05) across the entire wall of the renal artery, in the media of the carotid artery, and in the media and adventitia of the common iliac artery. Samples from the vena cava show significant increases in collagen fibril cross sectional area across the vessel wall (p less than .005). The only areas studied which did not show significant changes were the intimal and adventitial regions of the common carotid artery. The observed changes may be contributory to the decreased arterial wall strength typical of the syndrome.

Adult↗