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Biomedical subjects

S Hewitt

Publications and source records attributed to S Hewitt.

At least 55 records · Page 3Linked to original sources

Erythrocyte autoantibodies, autoimmune haemolysis, and myelodysplastic syndromes.

Immunohaematological investigations were carried out in 46 patients with erythrocyte autoantibodies associated with myelodysplastic syndromes. Eight patients had refractory anaemia, 17 refractory anaemia with ring sideroblasts, 11 refractory anaemia with excess of blasts, four chronic myelomonocytic leukaemia, five refractory anaemia with excess of blasts in transformation and one could not be classified. Standard agglutination direct antiglobulin tests showed that the red cells were most often coated with IgG and C3d, though increased amounts of IgM or IgA were also found in 15 of 35 cases (43%) when the more sensitive enzyme linked method was used. The IgG antibodies were predominantly of IgG1 subclass. Clinically important autoimmune haemolysis occurred in 15 patients, and was of "warm", "cold," and "mixed" types in seven, four, and four cases, respectively: it is important to recognise its presence in view of the good response to treatment. The increased incidence of erythrocyte autoantibodies in myelodysplastic syndromes is thought to be one manifestation of disturbed immune homeostasis.

Aged↗

Leuprolide acetate in the treatment of refractory or persistent epithelial ovarian cancer.

Leuprolide acetate (Lupron, TAP Pharmaceuticals, North Chicago), a gonadotropin-releasing hormone analogue, was administered subcutaneously at a 1-mg dose for a minimum of 8 weeks to 23 patients with refractory epithelial ovarian cancer. Eighteen of these patients were evaluable. There were no complete responses. Four patients (17%) had a partial response, with a median duration of 52 weeks. Three of six patients with grade 1 carcinomas had a partial response and two had stabilized disease. There was only one response among 15 patients with grade 2 or 3 disease. Therapy was well tolerated, with three patients complaining of hot flashes and two of mild pedal edema. Leuprolide acetate thus shows evidence of antitumor activity against refractory grade 1 epithelial adenocarcinoma of the ovary. Further trials with larger numbers of patients should be conducted.

Adult↗

Wound hematoma: prophylaxis with topical thrombin.

We studied 123 patients having elective exploratory laparotomy through a midline vertical incision for gynecologic disease; patients were randomized to receive wound irrigation with either saline or topical thrombin before closure of the incision. Seven patients were not evaluable. No patient received low-dose heparin therapy perioperatively. No patient in either group had a clinically significant wound hematoma or disruption. Minor wound hematomas were more common in the saline group, a finding that approached statistical significance. Blood coagulation profiles were not different in the two groups either preoperatively or postoperatively. Topical thrombin is probably not clinically useful in preventing wound hematomas in patients who do not receive perioperative treatment with low-dose heparin; however, it seems to be safe for application to open wounds.

Administration, Topical↗

An enzyme-linked direct antiglobulin test for assessing erythrocyte bound immunoglobulins.

An enzyme-linked direct antiglobulin test (DAGT) for assessing erythrocyte-bound IgG, IgM and IgA is described. The test is carried out in microtitre plates using heavy chain-specific, alkaline phosphatase-linked, goat anti-human globulin reagents with p-nitrophenyl phosphate as substrate. Results are expressed in optical density (OD) units per 3.6 X 10(7) red cells. The method is reproducible, with coefficients of variation of 0.056, 0.093 and 0.087 for IgG, IgM and IgA respectively. The linear relationship between the amount of red cell-bound antibody and the OD reading for each immunoglobulin class shows that the method is suitable for quantitative studies. Healthy individuals were found to have small amounts of immunoglobulin bound to their red cells with mean values of 0.251, 0.087 and 0.128 OD units per 3.6 X 10(7) red cells for IgG, IgM and IgA respectively; there was no difference between male and female subjects. In the clinical situation, the enzyme-linked DAGT was considered to show significantly increased amounts of cell-bound immunoglobulin when the results were more than three standard deviations above the mean and the quantitative results permitted an accurate assessment of the progress and response to treatment of patients with autoimmune haemolysis.

Adolescent↗

Patients with red cell autoantibodies: selection of blood for transfusion.

The provision of blood for transfusing patients whose sera contain red cell autoantibodies requires considerable expertise. Over 8 years, 3888 samples from 2149 patients were examined; the varying clinical presentation necessitated a flexible investigative approach. The autoantibodies showed evidence of blood group specificity in 706 patients (32.9%), usually within the Rh system for warm reacting antibodies, whereas cold antibodies were mostly anti-I. Concomitant alloantibodies were detected by noting varying reaction strengths during antibody investigation and compatibility testing, and by absorption techniques using autologous or selected allogenous red cells. Alloantibodies were found in 294 patients (13.7%); the most frequent were anti-E and anti-K. Compatibility tests were performed on SAG-M donor blood of suitable ABO group, similar Rh genotype, Kell negative and lacking antigens to any alloantibodies detected. All units of blood were incompatible by at least one technique and were issued as 'not compatible but considered suitable'. A total of 7052 units was issued for 1685 patients; no haemolytic reactions were reported. It was concluded that blood can be safely given to patients with autoantibodies, even in serologically complex cases, providing adequate investigations are carried out.

Anemia, Hemolytic, Autoimmune↗

Small quantities of erythrocyte bound immunoglobulins and autoimmune haemolysis.

Enzyme linked and radioimmune direct antiglobulin tests (DAGTs) were used to assess red cell bound IgG, IgA, and IgM in 585 patients referred to an immunohaematology reference centre. One hundred and fifty eight patients with less than or equal to 200 mol IgG and small amounts of IgA and IgM coating their red cells were studied in detail. The presence of autoimmune haemolysis was determined from the clinical, haematological, and biochemical findings; it occurred in at least 25% of the 158 patients, the degree varying widely. There was a highly significant association between small increases in cell bound immunoglobulins and the presence of autoimmune haemolysis. Immunoglobulins of IgG, IgA, and IgM classes could produce autoimmune haemolysis when the classical agglutination DAGTs were negative; the IgA and IgM were usually found in association with IgG. The haemolytic effect was enhanced by the presence of complement and combinations of immunoglobulin classes on the red cells.

Anemia, Hemolytic, Autoimmune↗

Major morbidity after pelvic exenteration: a seven-year experience.

Thirty-eight patients underwent pelvic exenteration at the University of South Florida during the last seven years. The majority of the operations were performed for recurrent carcinoma of the cervix, and the operative mortality was 5.3%. Twenty-one patients developed major morbidity in the postoperative period, and 11 with complications involving the gastrointestinal or urinary tract required reoperation. Multivariate logistic regression analysis demonstrated a correlation between the amount of pelvic radiation, type of pelvic floor, type of pelvic drain, amount of blood loss, race, and the occurrence of serious postoperative morbidity. Strategies to avoid serious postoperative morbidity are discussed.

Adult↗

Conduction tissue in the transplanted human heart.

Eleven orthotopically transplanted human hearts have been examined at retransplantation or necropsy. They were selected to cover the period up to 3 years after transplantation. The recipient SA node was examined in six, the donor SA node in eight and the AV conduction tissue in all eleven. Each of these areas has been examined by serial sectioning. All the conduction tissue is discretely involved in rejection and this involvement is no more severe than in the adjacent myocardium. In the AV tissue there is a tendency for the peripheral parts to be more frequently involved than the proximal. There is little evidence of permanent structural damage to the AV tissues by recurrent episodes of mild to moderate rejection. In the atrial nodes there is about a 50 per cent chance of surgical or procurement damage to both the recipient and the donor tissue.

Adult↗

Autoimmune hemolysis: a critical review.

Autoimmune hemolysis is defined as a shortening of erythrocyte lifespan due to antibodies directed against the individuals own red cells. This autoantibody production (by B lymphocytes) is thought to result from deficient activity of suppressor T lymphocytes. The rate of erythrocyte destruction depends on the properties of the autoantibodies and on the activities of the complement and mononuclear phagocyte systems: anemia results when destruction outweighs marrow production. Autoimmune hemolysis, which may be primary or secondary, is classified into "warm," "cold," and "mixed" types. The hemolysis associated with pregnancy. Donath-Landsteiner antibodies, of mixed type, and in children, is treated in detail. Current treatment is with immunosuppressive drugs, surgery, and plasma exchange, though immunomanipulation may become important in the future; blood transfusion may be a life-saving adjunct to other therapy.

Adolescent↗

Effect of blood on the activity and persistence of antigen induced inflammation in the rat air pouch.

The hypothesis that haem iron derived from synovial microbleeding has a proinflammatory effect on the synovial membrane was tested by adding autologous whole blood and fractions derived from it to a naturally remitting rat air pouch model of allergic inflammation. The induction of such a subcutaneous air pouch produces a cavity lined by mesenchymal cells comparable to the synovial membrane. Autologous whole blood was found to prolong a low grade inflammatory state, this effect being attributable to a red cell component, most probably haem iron. Whole blood in the absence of an inflammatory stimulus does not have this effect, indicating that the mechanism is one of prolonging or promoting existing allergic inflammation, rather than inducing an inflammatory response.

Air↗

Adenine nucleotide concentrations in patients with erythrocyte autoantibodies.

Erythrocyte adenine nucleotide concentrations were measured in 154 patients with erythrocyte autoantibodies and 811 normal subjects using a luciferin-luciferase bioluminescent assay. The patients were initially divided into haemolysing and non-haemolysing groups. Red cell adenosine triphosphate (ATP) concentrations were significantly raised in the 96 patients with active haemolysis compared with the normal subjects and with the 58 patients in the non-haemolysing group. Although the patients categorised as non-haemolysing had higher ATP values than the normal subjects, this was because several patients had the anaemia of chronic disorders, which is associated with a shortened red cell life. Measurement of red cell ATP was a useful indicator of mean erythrocyte age and a raised value in patients with erythrocyte autoantibodies reflected active haemolysis.

Adenosine Diphosphate↗

Enzyme linked direct antiglobulin tests in patients with autoimmune haemolysis.

Enzyme linked and agglutination direct antiglobulin tests were carried out on blood samples from 219 patients suspected of having autoimmune haemolysis. The enzyme linked tests were more sensitive: they could detect the small amounts of IgG, IgA, and IgM which are normally present on red cells and showed increased amounts of cell bound immunoglobulins in patients with Coombs test negative autoimmune haemolysis. Many patients had immunoglobulins of more than one class bound to their red cells; considering the degree of haemolysis in individual patients, it appeared that the different immunoglobulin classes acted synergistically in effecting red cell destruction, even in amounts too small to be detected by the agglutination tests. In patients with cold reacting autoantibodies and complement coating of the red cells active haemolysis was found (with one exception) where IgM was detected on the cells by the enzyme linked method. Elution studies indicated that immunoglobulins detected just by the enzyme linked techniques were red cell antibodies. Both enzyme linked and agglutination tests were negative in 66 patients: 61 of these had no evidence of haemolysis, and in the other five the haemolysis was not autoimmune in origin.

Alkaline Phosphatase↗

Autoimmune haemolysis in childhood and adolescence.

The clinico-pathological features of 42 children with autoimmune haemolysis are described. Over 65% of cases were seen before their 5th birthday. In this group males predominated by the ratio of 2.5:1, but in the older children both sexes were equally affected. The incidence decreased from 1 in 188 X 10(3) in young males to 1 in 1,780 X 10(3) in children over 10. Cases were classified serologically. Of particular note was the frequency of Donath-Landsteiner haemolysis which equalled that due to warm autoantibodies; together these groups made up 79% of the total cases. Most haemolytic episodes followed an acute infection. This was frequently mild and often involved the upper respiratory tract; in only 2 patients was haemolysis associated with underlying collagenosis. Typically there was a sudden onset of pallor and malaise; jaundice, splenomegaly and hepatomegaly were found in about half the subjects. Haemoglobinuria was characteristic of Donath-Landsteiner haemolysis. The illness was severe, with Hb levels falling below 6.0 g/dl in 28 patients. Prednisolone, blood transfusion and, where indicated, antibiotics were usually effective in treating the illness, with splenectomy reserved for cases where this treatment was unsatisfactory. In several individuals no treatment was required. Recovery was rapid, and complete recovery occurred in 83% of patients, usually within 6 months. Although 2 patients died, a generally optimistic prognosis can be given, particularly in the absence of an underlying chronic disorder.

Adolescent↗

Paroxysmal nocturnal haemoglobinuria. A clinicopathological study of 26 cases.

26 patients, 13 male and 13 female, with paroxysmal nocturnal haemoglobinuria (PNH) are described. The diagnosis was based on the finding of a positive Ham's test. PNH developed in 4 patients with aplastic anaemia, and 3 patients with established PNH developed marrow hypoplasia during the course of the disease. In 2 cases autoimmune haemolysis was also present; this association has not been described previously. The majority of patients presented with anaemia and dark urine, or with evidence of thrombosis. A high index of suspicion was needed to avoid missing the diagnosis. Haemolytic crises were usually precipitated by infection, and renal failure requiring dialysis sometimes resulted; a positive direct antiglobulin test was often found at times of increased haemolysis. Thromboses were the most frequent complication, and when intra-abdominal vessels were affected, pain was particularly troublesome. The disease had a widely variable course; 4 patients made a complete recovery and 10 died, 8 from thrombotic complications and 2 from infections associated with marrow hypoplasia. Survival ranged from 1 year to 30 years and the median survival in those who died was 3.5 years.

Adolescent↗