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Biomedical subjects

G D Lowe

Publications and source records attributed to G D Lowe.

At least 199 records · Page 11Linked to original sources
PubMed1990

Capacity to produce interleukin 2 is impaired in haemophilia in the absence and presence of HIV 1 infection.

Capacity to produce interleukin-2 (IL-2) was measured in haemophiliacs from a well-defined treated cohort. Patients were selected on the basis of HIV-1 antibody status, mean annual dose of clotting factor and liver disease severity. T-cell subsets and peripheral blood mononuclear cell proliferation to Mycobacterium tuberculosis purified protein derivative (PPD) were also measured. Haemophiliacs had reduced IL-2 production, independent of HIV-1 antibody status, mean annual dose of clotting factor concentrate used and liver disease severity. In HIV-1 antibody positive patients reduced levels correlated with PPD proliferative responses (r = 0.6, P = 0.04) and CD8 + ve (r = 0.5, P = 0.05) but not CD4 + ve cell numbers (r = 0.3, P = 0.2). No such correlations were seen in HIV-1 antibody negative patients. Reduced IL-2 production in HIV-1 antibody negative haemophiliacs was due to a qualitative defect. In HIV-1 positive patients a qualitative defect in T lymphocytes that selectively proliferate in response to PPD was observed. CD4 + ve cell numbers were reduced in HIV-1 positive patients.

Adult↗
PubMed1990

Coagulation disturbances in cancer of the breast and colon measured with specific monoclonal antibody enzyme immunoassay for fibrin-fibrinogen degradation products.

Disturbances of coagulation were measured in breast cancer, colon cancer and benign breast disease using an enzyme immunoassay against total plasma fibrinogen and fibrin degradation products (TDP). Results were compared with measurements of fibrinopeptide A (FPA) and of serum fibrinogen-related antigen (FRA). Plasma TDP before surgery was significantly higher in colon cancer than in breast cancer patients (p = 0.0009) or in benign breast disease (p = 0.0292). A post-operative rise in TDP at 4 months (colon cancer) or 9 months (breast cancer) was associated with early recurrent disease (p less than 0.0173 for colon cancer, p less than 0.1835 for breast cancer). No such association was noted with FPA or FRA measurements. TDP may prove to be of value in detecting activation of coagulation by malignant disease.

Antibodies, Monoclonal↗
PubMed1990

Further evidence that the residual vWf:Ag in porcine FVIII:C induces human platelet aggregation.

Porcine or bovine factor VIII concentrates (FVIII:C) have been used during the past 3 decades to control bleeding in patients who have developed antibodies to human factor VIII. Since current preparations of animal FVIII:C are not known to transmit infectious agents such as hepatitis or human immunodeficiency virus, they are of potential therapeutic interest. A purified porcine FVIII:C (Hyate:C) is now widely used as an alternative to human FVIII:C in patients with inhibitor. Unlike earlier preparations of porcine FVIII:C, thrombocytopaenia is rare with the current preparation. Nonetheless, it causes the aggregation of human platelets in vitro. Our aim was to identify precisely the plasma factor which induces platelet aggregation. The effects of commercial porcine FVIII:C, porcine fibrinogen, porcine fibronectin and the corresponding preparations from human origin on platelet aggregation were studied. Platelet aggregation was quantified by measuring the fall in single platelet count in human whole blood. Of these preparations, only porcine FVIII:C (0.1-1 U/ml) and porcine fibrinogen (80-600 micrograms/ml) induced a fall in single platelet count of up to 85% due to aggregation. The extent of aggregation was directly proportional to the amount (0.007-0.1 U/ml test aliquot) of residual von Willebrand factor antigen (vWf:Ag) in the preparations. A monoclonal antibody to vWf:Ag inhibited the aggregation. We believe that the aggregation of human platelets induced in vitro by porcine FVIII:C is mediated by vWf:Ag which also may be responsible for thrombocytopaenia reported following administration of porcine FVIII:C in vivo.

Animals↗
PubMed1990

Whole blood viscosity and red cell filterability as factors in sensorineural hearing impairment in the elderly.

Deficiencies in blood supply can lead to impairments in cochlear function. We have reported significant associations of both measures of whole blood viscosity and derived measures of red cell rigidity with hearing threshold levels in individuals with sensorineural hearing impairments. This paper describes direct measures of red cell filterability in a group balanced across the variables of hearing threshold level and age to facilitate dissociation of the effects of factors correlated with age. After controlling for effects of age, sex and social class, there were strong correlations between whole blood viscosity at high shear rate and hearing threshold levels at 250, 500, and 1,000 and 2,000 Hz. At 4,000 and 8,000 Hz, hearing threshold level was related to red cell filterability. When the data are divided into subgroups by age, the younger age group exhibited a pattern similar to the overall one, but in the older age group the effect of red cell filterability was more apparent, extending down to 1,000 Hz. The data support a strong association between aspects of blood rheology and sensorineural hearing impairment, but in a more complex manner than suggested by previous studies. They imply that there are two processes associated with sensorineural hearing impairment, one of which can be considered as due to bulk rheological properties, while the other appears more related to the properties of individual red cells. The bulk properties are more important at lower frequencies, while the cellular properties are more influential at higher frequencies.

Aged↗
PubMed1990

Evaluation of red cell deformability by a filtration method in type 1 and type 2 diabetes mellitus with and without vascular complications.

Previous studies of red cell deformability (RCD) in diabetic patients have produced conflicting results. We have therefore reassessed this problem with the Carri-Med Filtrometer, which measures RCD independently of the rate of clogging of the filter. The initial red cell filtration ratio relative to buffer (mean +/- SD) of 69 diabetic patients (28 type 1 and 41 type 2) was significantly impaired in both type 1 (0.470 +/- 0.047) and type 2 diabetic patients (0.488 +/- 0.065), when compared to 66 non diabetic control subjects (0.540 +/- 0.032; both p less than 0.001). A significant difference in RCD was noted between type 1 and type 2 diabetics (p less than 0.03), but no association with vascular complications was found. No significant correlations were noted between RCD and the duration of diabetes, age, HbA1, leucocyte count, or mean red cell volume. However RCD was inversely related to mean red cell haemoglobin concentration (r = -0.43, p less than 0.01). Diabetics had significantly lower mean red cell volume and significantly higher mean cell haemoglobin concentration than non-diabetics, but these changes could not explain the difference in RCD, which may be related to alterations in the red cell membrane.

Adult↗
PubMed1990

Analysis of cytogenetic effects in bone-marrow cells of rats subchronically exposed to smoke from cigarettes which burn or only heat tobacco.

The genotoxic effects of 90-day nose-only exposures to smoke from new cigarettes, which heat but do not burn tobacco (New), or from reference cigarettes, which burn tobacco, were evaluated in Sprague-Dawley rats by examining the cytogenetic endpoints of sister-chromatid exchanges (SCE), chromosome aberrations, and micronuclei in bone-marrow cells. The concentrations of wet total particulate matter (WTPM) and carbon monoxide in the smoke from both cigarette types were similar. The mainstream smoke from both New and reference cigarettes was adjusted to WTPM concentrations of approx. 200 and 400 micrograms/l for low and high smoke exposure. Rats were exposed to smoke 1 h per day, 5 days per week for 13 consecutive weeks. Inhalation of smoke by the exposed animals was confirmed by analysis of blood carboxyhemoglobin and plasma nicotine. Examination of bone-marrow cells following the final day of exposure showed that smoke from neither the New nor reference cigarette induced a positive response in the SCE, chromosome aberration, or micronucleus assays in rats.

Animals↗
PubMed1989

In vivo measurements of fibrin formation and fibrinolysis in operable breast cancer.

Fibrin formation and fibrinolysis were estimated in 89 breast cancer patients by measurement in plasma of Fibrin Fragment B beta 15-42 and Fibrinopeptide A (FPA), serum Fibrin(ogen) Degradation Products (FDPs) and plasminogen activator by Fibrin Plate Lysis Assay. Results were compared with (a) 26 patients with benign breast diseases; and (b) 45 healthy factory workers. FPA, FDP and B beta 15-42 levels were elevated in both breast cancer patients and benign disease patients, but there were no significant differences between these two groups. Cancer stage, patient age and smoking habits did not affect these results, but Oestrogen Receptor (ER) positive patients had higher B beta 15-42 values than ER negative patients (p = 0.017). These results show that fibrin formation is enhanced preoperatively in patients with either benign or malignant breast disease. The fibrinolytic response to activated coagulation may be relatively deficient in breast cancer. The roles of malignancy, stress and other factors in the causation of these abnormalities require further assessment.

Breast Neoplasms↗
PubMed1989

Blood viscosity and hearing levels in the Caerphilly Collaborative Heart Disease Study.

Data from 342 men who are participants in the Caerphilly Collaborative Heart Disease Study were used to replicate a previous report of a significant relationship between measures of whole-blood viscosity and hearing levels in persons with sensorineural hearing impairment. In the unselected data, there were significant relationships between measures of whole-blood viscosity at high shear rates and hearing threshold levels at 2000 and 4000 Hz, even after accounting for the effects of age and socioeconomic group. In a subset of the data containing 124 persons selected on the basis of likely sensorineural hearing impairment, there were significant relationships between whole-blood viscosity and hearing level at all frequencies, with stronger effects at the higher frequencies. The data support the contention of a potentially important relationship between whole-blood viscosity and sensorineural hearing impairment.

Audiometry, Pure-Tone↗
PubMed1989

Dipyridamole inhibits red cell-induced platelet activation.

We have recently shown that red blood cells can induce spontaneous platelet aggregation (SPA) in whole blood ex vivo, which could be inhibited by dipyridamole. Since this drug, at therapeutic doses is not an effective inhibitor of platelet aggregation in platelet rich plasma, the inhibition of platelet interaction with the red cell was thought to be the mechanism of its action. Values for the percentage fall in the single platelet count due to SPA in whole blood after 3 and 6 min rollermixing were: control 15 +/- 2.2 and 42 +/- 2.9; 6 microM dipyridamole 6 +/- 1.1 (P less than 0.001) and 31 +/- 2.6 (P less than 0.01); 12 microM dipyridamole 2 +/- 0.9 (P less than 0.0005) and 22 +/- 2.3 (P less than 0.0005) (mean +/- SEM, n = 10). Electron microscopic observation revealed that the aggregation involves an initial platelet adhesion to the red blood cell; the adherent platelets then become activated and serve as foci for the growing aggregates. Dipyridamole appeared to inhibit the initial platelet adhesion to the red cell (the principal trigger mechanism for SPA) which may mimic the initiation of thrombosis in some situations in vivo. The inhibitory effect of dipyridamole on the platelet-red cell interaction suggests that this drug has antithrombotic potential in situations where red blood cells have a trigger role in platelet activation and may explain why the drug has been more effective in some situations than in others.

Adult↗
PubMed1989

Monoclonal antibody immunoassay in the study of thrombogenicity of preclotted and gelatin-impregnated aortic prostheses.

The Dimertest Enzyme Immunoassay has been used to compare the degree of thrombogenicity of the standard knitted Dacron prosthesis (n = 10) and the gelatin-impregnated Dacron prosthesis (n = 10) after infrarenal aortic reconstruction. After surgery there was a similar rise in cross-linked fibrin degradation products with both types of prostheses. Although on the third day the D-Dimer level in the gelatin-impregnated prosthesis was lower, there was no significant difference in the D-Dimer level at six weeks. This suggests that the potential risk of thrombogenicity in the gelatin-impregnated prosthesis is similar to the standard preclotted type.

Aged↗
PubMed1989

Platelet aggregation inhibitory effects of the new positive inotropic agents pimobendan and UD CG 212 in whole blood.

A method is described for studying platelet function in human whole blood immediately after venepuncture in order to evaluate the antithrombotic potential of new pharmacological agents. In this method, platelet aggregation is quantified by measuring the fall in single platelet count, by using a whole blood platelet counter. We have investigated the platelet aggregation inhibitory effects of the new positive inotropic agents pimobendan and UD CG 212 (reported to be Ca++ sensitisers and phosphodiesterase inhibitors), alone and in combination with dipyridamole. Venous blood was drawn directly into prewarmed (37 degrees C) plastic syringes containing anticoagulants (3.2% trisodium citrate solution) plus a platelet aggregation inhibitor. Spontaneous platelet aggregation (SPA) was studied by roller mixing aliquots of blood in the collecting syringes for 6 min at 37 degrees C. Collagen induced platelet aggregation was studied by incubating aliquots of blood with 1 microgram/ml collagen on a shaking water bath for 3 min. In the absence of an inhibitor, there was a 50% fall in single platelet count due to SPA and a 65% fall was induced by collagen. Both SPA and collagen induced aggregation responses were inhibited by pimobendan (0.5-10 microM) and UD CG 212 (0.5-10 microM), in a dose dependent manner. A combination of 10 microM dipyridamole with 2 microM pimobendan or UD CG 212 was markedly a more effective inhibitor of platelet aggregation than a high dose of either inhibitor alone. It is suggested that the present method is simple and rapid, with minimal sample processing, and therefore the results may be protected from serious artifacts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Response to desmopressin in type IID von Willebrand's disease.

Dominant transmission of a variant of von Willebrand's disease (vWD) with aberrant polymerization of von Willebrand factor (vWF) has been identified in a Scottish family. Multimer analysis of plasma vWF from the propositus and her father revealed an identical pattern to that previously reported in families designated as type IID vWD. There is loss of the larger multimers and presence of an intermediate subsidiary band not seen in normal subjects or other vWD variants. Platelet/vWF interaction induced by ristocetin is not enhanced in these cases and the platelet vWF shows the same aberrant multimer pattern as plasma vWF. DDAVP infusion in two affected members of the Scottish family and in one of the index cases produced a rise in plasma vWF antigen and factor VIII. Higher molecular weight vWF multimers appeared transiently after infusion of desmopressin (1-deamino-8-D-arginine vasopressin, abbreviated DDAVP) coincident with shortening of the bleeding time. The platelet counts did not change after the DDAVP infusions. DDAVP should be considered for management of bleeding in this variant of von Willebrand's disease.

Adult↗
PubMed1989

Histometric studies on cellular infiltrates of tuberculin tests in patients with haemophilia.

The number of microanatomical location of CD4 and CD8 lymphocytes, of cells bearing receptors for I12 and transferrin, and of monocyte/macrophages in the dermis at the site of a tuberculin test were measured in 13 patients with haemophilia (10 seronegative and three seropositive for human immunodeficiency virus (HIV]. The overall density of lymphocytes in the perivascular and diffuse parts of the infiltrate was similar to that reported in other groups of subjects without evidence of immunosuppression. The CD4:CD8 ratio of the infiltrating lymphocytes throughout the section showed an inverse relation with clotting factor consumption. There was no significant change in the CD4:CD8 ratio in the diffuse infiltrate at various levels into the dermis in tuberculin reactions in patients with haemophilia, unlike healthy controls and other groups with no evidence of immunosuppression, who have previously been shown to have increasing CD4:CD8 ratio with increasing depth into the dermis. The number of cells bearing receptors for I12 and transferrin and of monocyte/macrophages was related to total lymphocyte density in the infiltrate. There was no evidence of serious impairment of the cell mediated response to a long term recall antigen, but the relatively low preponderance of CD4 lymphocytes in the diffuse infiltrate, particularly in the deeper dermis, may be the earliest indicator of impending immunosuppression.

CD4-Positive T-Lymphocytes↗
PubMed1989

Age and blood cell rheology.

The identification of the rheological variables responsible for alterations in capillary blood flow caused by the aging process could help explain why the incidence of vascular disease increases with age. Using new techniques for the separation and micropore filtration of the haemocellular subpopulations in 110 subjects aged 21-84 years, the aim of this study was to show to what extent, if any, age influences blood cell deformability. The filterability of mononuclear leucocytes decreased with age (r = 0.25; p less than 0.001), whereas the filterability of polymorphonuclear leucocytes or erythrocytes did not change significantly with age.

Adult↗
PubMed1989

Comparison of the effect of aspirin and choline magnesium trisalicylate on thromboxane biosynthesis in human platelets: role of the acetyl moiety.

Parameters of platelet thromboxane biosynthesis were measured 24 h after ingestion of equivalent salicylate doses (500 mg) of aspirin (ASA) and choline magnesium trisalicylate (CMT), a non-acetylated salicylate. In random order, 10 healthy volunteers received these drugs on 2 separate days, 2 weeks apart. While ASA significantly prolonged bleeding time, and decreased plasma thromboxane generation and serum thromboxane B2 levels, CMT failed to produce such effects. Thus CMT, which lacks an acetyl moiety in its structure, has no inhibitory effect on platelet thromboxane biosynthesis, and may therefore be considered safer than ASA for therapeutic use, when inhibition of platelet function can be hazardous.

Adult↗