Biomedical subjects
Publications and source records attributed to C A Ludlam.
Two batches of heat-treated factor VIII concentrate were found to contain anti-HIV-positive plasma donations. The batches were dry-heat-treated at 68 degrees C for 2 and 24 h, respectively. No HIV seroconversions occurred in 13 susceptible haemophiliacs receiving a total of 540 bottles of these factor VIII preparations.
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During the collection of samples for plasma beta-thromboglobulin (beta-TG) determination, it is well established that artificially high values can be observed due to in-vitro release. To estimate the reliability of a single beta-TG measurement, blood samples were collected simultaneously from both arms on two separate occasions in 56 diabetic patients selected for a clinical trial. From each arm, blood was taken into two tubes containing an anticoagulant mixture with (tube A) and without (tube B) PGE1. The overall mean value of B-TG in tube B was 1.14 times higher than in tube A (p less than 0.01). The markedly large between-arms variation accounted for the most part of within-subject variation in both tubes and was significantly greater in tube B than in tube A. Based on the difference between B-TG values from both arms, the number of subjects with artificially high B-TG values was significantly higher in tube B than in tube A on each occasion (overall rate: 28% and 14% respectively). Estimate of between-occasions variation showed that B-TG levels were relatively stable for each subject between two occasions in each tube. It is concluded that the use of PGE1 decreases falsely high B-TG levels, but a single measurement of B-TG does not provide a reliable estimate of the true B-TG value in vivo.
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A case of composite lymphoma consisting of Hodgkin's disease and B cell lymphocytic lymphoma is described. A diagnosis of lymphocyte predominant Hodgkin's disease was made initially by histology. The presence of a composite lymphoma was only appreciated once immunohistochemistry was available. The findings illustrate the importance of the use of immunological markers for the accurate diagnosis of lymphoma.
Little has been written about the effects of hemophilic arthropathy on the function and radiography of the upper limb. Therefore, 14 moderate and 19 severe hemophiliacs between the ages of 10 and 57 years were examined clinically and radiographically. The extent of the arthropathic changes in the shoulders, elbows, wrists, and hands were classified according to the system proposed by the World Federation of Hemophilia. The severity of the arthropathy increased with the age of the patient and with the number of hemarthroses recorded, although the correlation between these parameters was variable. The elbow joints were the site of recognizable arthropathy in 87% of the cases, with a slight preponderance for the nondominant side. The glenohumeral and wrist joints were affected in a small proportion of patients, although symptoms were rarely experienced. Hemorrhages affecting the hands were uncommon and produced arthropathy infrequently.
The present study was designed to investigate the survival of platelets of differing densities in normal and post-splenectomized subjects. Autologous platelets, labelled with 111In-oxine, were reinjected into normal subjects (n = 12); 63% were recovered in the circulation and their survival curve was linear with a T 1/2 of 4.5 d. When the platelets were layered onto a continuous Percoll gradient, they formed a band extending between 1.040 and 1.080 g ml-1. After fractionation of the gradient the specific radioactivity of 111In platelets recovered was measured. The specific activity of low density platelets (average 1.050 g ml-1) decreased rapidly with a T 1/2 of 2.0 d, whilst medium density platelets (average 1.060 g ml-1) survived with a T 1/2 of 4.5 d; high density platelets (average 1.073 g ml-1) exhibited a T 1/2 greater than 5.0 d. This latter population of high density platelets also showed a significant increase in specific activity on the first day following injection. In post-splenectomy subjects a similar relationship between density and 111In associated activity was observed but no increase in the specific activity of the dense platelets on day 1 was observed. We conclude that high density autologous 111In-platelets are preferentially retained in the spleen and have a more prolonged survival than those of lower density.
This study was designed to assess the density characteristics of platelets from controls (N = 10) and three groups of diabetics (N = 32) exhibiting various degrees of glycemic control. With continuous gradients of Percoll, platelets from controls and diabetics (N = 8) with an HbA1 less than or equal to 9% formed a band extending from 1.0625 g/ml to 1.0925 g/ml with a mean platelet density of 1.0775 g/ml. In the two groups of diabetics with HbA1 greater than or equal to 10%, there was an increase in the proportion of low-density platelets recovered on the gradients and the mean platelet density was reduced to 1.0750 g/ml (HbA1 = 10-13%) and 1.070 g/ml (HbA1 greater than or equal to 14%). All three groups of diabetics had normal levels of intraplatelet ATP/ADP and beta-thromboglobulin. It is unlikely that in vivo degranulation of platelets after activation was responsible for the altered density profiles. We propose that abnormal platelet subpopulations with low density but normal intraplatelet granule content were responsible for the changed density profiles.
Fifteen haemophiliac patients acquired antibodies to human T-lymphotropic virus type III during 1984. One batch of factor VIII concentrate given to all these patients is presumed to be the cause of the seroconversion. A further eighteen patients who received the same batch did not seroconvert and one other patient became seropositive but had not received this batch. Before transfusion of the implicated batch the patients had low T-helper-cell numbers and T-helper/suppressor ratios; neither changed in those who seroconverted. The probability of seroconversion was independently related to the pre-existing low T-helper/suppressor ratio, the number of vials of the implicated batch transfused, and the total annual factor VIII consumption. Ten other patients received a batch of factor IX concentrate from the same donor plasma; none of these patients seroconverted.
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Markers of the immune system were examined in 47 patients with haemophilia A and B who had been treated exclusively with blood products from a population apparently free from acquired immunodeficiency syndrome (AIDS). In haemophilia A the absolute number of T helper cells was depressed, resulting in a reduction in the helper/suppressor ratio in about half the patients. The serum IgG and IgA concentrations were raised and the serum IgG correlated with serum alanine aminotransferase. In haemophilia B, the helper/suppressor ratio was also depressed but this was attributable to a slight increase in the mean suppressor cell number and a slight decrease in the helper cells. These observations suggest that the abnormalities result from transfusion of foreign proteins and not from a specific infective agent and, further, that individuals may differ in susceptibility to the induced disturbances of immunity.
In a group of six normal male volunteers, infusion of DDAVP, venous occlusion and exercise were shown to increase plasma levels of factor VIII and plasminogen activator, activity and antigen, to different extents and at differing rates. Any mechanisms suggested to explain release of these proteins by various stimuli should account for such differences. All three stimuli could also increase plasma levels of prostacyclin metabolites, although this was only significant for high doses of DDAVP. Other potential endothelial markers, such as fibronectin and thrombospondin, showed no specific increase after any of the stimuli.
Psychiatric morbidity, relevant symptoms and satisfaction with communication were assessed in patients suffering from malignant lymphoma. Before treatment started 15 of 40 patients had clinically significant psychiatric morbidity. Treatment, in its early stages, was not associated with a significant change in mean psychiatric morbidity scores but there was a decrease in ratings of concern about illness and an increase in ratings of nausea. Eleven of 31 patients seen for a second interview reported dissatisfaction with some aspect of communication with the medical staff. The findings suggest that emotional distress can be contained with a policy of frank communication; nevertheless dissatisfaction is common, being associated with initial less concern, good general health and neurotic personality traits. Personality assessment should be incorporated in future studies of doctor-patient communication.
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During each of the four-year periods 1971-1975 and 1975-1979, the annual incidence of hepatitis B infection has been assessed in 56 patients with haemophilia A by measuring plasma HBsAg, anti-HBs and anti-HBc levels. Infection rates of 7% and 9.5% per annum respectively were observed for each four-year period despite the screening of individual blood donations for HBsAg by techniques up to the sensitivity of reversed passive haemagglutination. The highest incidence of seroconversion was amongst severe haemophiliacs many of whom had received treatment predominantly with cryoprecipitate. Of the 16 patients in whom serological evidence of hepatitis B infection was obtained only one had an accompanying clinical episode of hepatitis. We conclude that haemophiliacs are still at high risk of infection by hepatitis B virus despite the screening of individual blood donors for HBsAg.
Traumatic neuropathies of the common peroneal nerve at the head of the fibula are relatively common, but nerve entrapment at this site is rarely encountered. A 55-year-old man with hemophilia A in whom common peroneal nerve entrapment occurred secondary to a probable muscle hematoma is described.