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Biomedical subjects

J C Gill

Publications and source records attributed to J C Gill.

At least 37 records · Page 2Linked to original sources
PubMed1995

Induction of immune tolerance in a 7-year-old hemophiliac with an anaphylactoid inhibitor.

BACKGROUND: Anaphylactic reactions were a rare complication of low purity VIII concentrates, but not with high purity VIII concentrates. CASE: 7 y/o WM with severe hemophilia A, received only cryoprecipitate and monoclonally purified VIII concentrates; developed post-infusional urticaria. A 2-Bethesda-unit inhibitor was detected. Generalized urticaria and bronchospasm following factor developed as the titer increased. Skin tests demonstrated reactivity to plasma derived VIII, but not recombinant VIII (rhVIII). Attempts at desensitization using rhVIII failed. ELISA revealed an anti-VIII IgE antibody. He was treated with a modified tolerance regimen using rhVIII starting at 500 U/day with aggressive premedication. The dosage increased by 200 U weekly as tolerated to a maximum of 100 U/kg/d without symptoms. RESULTS: His antibody titer decreased rapidly once he started 100 U/kg/d. Six months later, the inhibitor was < 1 Bethesda unit. CONCLUSION: Immune tolerance induction using a graduated dosage of rhVIII was successful.

Anaphylaxis↗
PubMed1994

Childhood stroke and lupus anticoagulant.

Despite extensive evaluation, the cause of many childhood ischemic strokes remains unexplained. Two children are reported with stroke and lupus anticoagulant. Both had family members with features of the antiphospholipid antibody syndrome. Children with unexplained ischemic stroke should be evaluated for lupus anticoagulant and anticardiolipin antibodies.

Antiphospholipid Syndrome↗
PubMed1994

Increased incidence of HLA-B40 group antigens in children with hemolytic-uremic syndrome.

Hemolytic uremic syndrome (HUS) develops in 25-30% of children infected with Escherichia coli strains that produce Shiga-like toxins, also known as verocytotoxins. Mild HUS also occurs in 1 in 4 of the other family members, suggesting a familial predisposition to HUS. To understand the possible genetic predisposition, the frequency of HLA antigens was evaluated in 30 children (12 boys, 18 girls; mean age 3.8 years) with HUS following a prodrome of bloody diarrhea. When compared to a blood donor population from the same geographic area and ethnic background, no significant differences were noted in the frequency of HLA-A, HLA-C, HLA-DR, and HLA-DQ antigens. However, the frequency of HLA-B40 and its splits (B60, 61, 41, 47) was significantly higher in the study population (corrected p < 0.005). The relative risk of developing HUS was 6.04 when HLA-B40 and HLA-B40 split products were present, and the risk increased to 8.5 when the analysis was extended to include the cross-reactive antigens B44 and B13. These HLA-B antigens share common amino acid sequences at positions 41-45 and 67-74 on the alpha-1 domain of the HLA class I molecule. Our data suggest that the inheritance of HLA-B40, its splits, and cross-reactive antigens increases the risk of developing HUS.

Adolescent↗
PubMed1993

Therapy of factor VIII deficiency.

In spite of the numerous complications of transfusion therapy, there is no doubt that development of convenient clotting factor concentrates for home care has revolutionized the care of patients with hemophilia. With the obvious exception of HIV infections and chronic hepatitis, the majority of patients have few clinically significant adverse side effects in spite of years of replacement therapy. The development of improved viral attenuation processes may have eliminated the viral contamination of these products, but this is yet to be confirmed. The recent breakthrough in the development of highly purified, genetically engineered FVIII products will, it is hoped, eliminate all of the complications of therapy with the exception of inhibitor development. The development of recombinant FVIII replacement should ultimately lead to the availability of reasonably priced products in potentially unlimited supply. If this can be achieved, we may be able to look forward to prophylactic infusion therapy for patients with severe FVIII deficiency and eliminate the significant complications that continue to occur even with prompt treatment of hemorrhage and thrombosis.

Blood Component Transfusion↗
PubMed1993

An unusual cause of cerebral venous thrombosis in a four-year-old child.

BACKGROUND AND PURPOSE: Inherited protein S deficiency has been associated with an increased risk of thromboembolic disease. It is possible that such a coagulopathy could predispose children to the development of strokes by permitting clot formation in response to stimuli that ordinarily would be insufficient to cause thrombus formation. CASE DESCRIPTION: We evaluated a previously well 4-year-old boy who developed cerebral venous thrombosis after suffering minor head trauma. Crossed-immunoelectrophoresis of his plasma showed a marked decrease of the free, active form of protein S. Family studies revealed that the patient's father and other paternal relatives had a similar abnormality of protein S. CONCLUSIONS: We suggest that the cerebral venous thrombosis in this child was initially precipitated by minor head trauma and pathological thrombus formation was then potentiated by inherited protein S deficiency. This case extends the clinical spectrum for protein S deficiency and emphasizes the importance of evaluating family members to establish a specific diagnosis and therapeutic intervention.

Blood Coagulation↗
PubMed1992

Heparin-induced thrombocytopenia in a child.

We describe a case of thrombocytopenia and deep venous thrombosis in a boy who received heparin to maintain patency of a central venous catheter. Measurement of the release of serotonin labeled with carbon 14 confirmed the presence of heparin-induced thrombocytopenia. Children receiving heparin therapy should be monitored for the possibility of heparin-induced thrombocytopenia.

Adolescent↗
PubMed1990

Protein C and protein S levels in two patients with acquired purpura fulminans.

Purpura fulminans (PF) is a cutaneous manifestation of a dramatic and deadly syndrome of systemic disseminated intravascular coagulation (DIC). It is characterized by microvascular thrombosis in the dermis followed by perivascular haemorrhage. Since two other related syndromes involve the protein C (PC) system, we undertook a serial study to investigate the levels of PC and protein S (PS) in two patients with acquired PF. Laboratory findings were consistent with DIC, and both patients were treated with blood replacement and heparin therapy. The levels of PC activity were very low during the initial 24-36 h after onset and gradually increased until returning to normal levels. The total and 'free' PS were also abnormal during the initial onset of PF. The total and free PS increased to normal after 4-6 d. Although the pathogenesis is not fully understood, the infection and sepsis appears to consume PC and PS selectively during the PF and DIC phase. Acquired PF appears to selectively involve the PC system in a similar fashion to two other syndromes of PF-like lesions.

Antithrombin III↗
PubMed1989

Structure of (20R)-20,21-epoxy-19-norpregna-1,3,5(10)-triene-3,17 beta-diol.

C20H26O3, Mr = 314.4, orthorhombic, P2(1)2(1)2(1), a = 10.25 (1), b = 25.36 (2), c = 13.11 (1) A, V = 3410.14 A3, Z = 8, Dx = 1.225 g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 0.45 cm-1, F(000) = 1352, T = 293 K. The structure was solved by direct methods and refined to R = 0.051 for 2384 reflections with F/signa(F) greater than 5. Both the crystallographically independent molecules are in one 20R configuration and confirm predictions based on mechanistic and stereochemical arguments. In the crystal lattice the molecules form a two-dimensional network of hydrogen bonds approximately perpendicular to c.

Antineoplastic Agents↗
PubMed1989

Hyponatremia and seizures in young children given DDAVP.

Desmopressin (DDAVP), a synthetic vasopressin, temporarily corrects bleeding abnormalities associated with mild hemophilia A, von Willebrand disease, and disorders of platelet function. The side effects of DDAVP are considered benign although most of its use has been in adults and older children. We report four children under the age of 2 years who became hyponatremic after intravenous DDAVP administration (0.3 microgram/kg). Three of them developed grand mal seizures. A review of the literature and these cases indicate that associated risk factors for hyponatremia after DDAVP administration include stress, surgery, anesthesia and narcotics (endogenous release of antidiuretic hormone), vomiting (loss of Na+), liver disease (hindered metabolism of DDAVP), renal tubular acidosis (chronically low serum Na+), multiple doses of DDAVP, and overhydration with hyponatremic fluids. DDAVP is not a benign drug in this age group and shows a serious potential for hyponatremia and seizures. Fluid restriction, avoidance of hyponatremic solutions, and close monitoring of serum electrolytes and urine output for at least 15-20 hr after the administration of DDAVP, when used in children under the age of 2 years, is warranted.

Deamino Arginine Vasopressin↗
PubMed1989

Molecular basis of human von Willebrand disease: analysis of platelet von Willebrand factor mRNA.

von Willebrand disease (vWD), the most common inherited bleeding disorder in humans, can result from either a quantitative or a qualitative defect in the adhesive glycoprotein, von Willebrand factor (vWF). Molecular studies of vWD have been limited by the large size of the vWF gene and difficulty in obtaining the vWF mRNA from patients. By use of an adaptation of the polymerase chain reaction, vWF mRNA was amplified and sequenced from peripheral blood platelets. A silent vWF allele was identified, resulting from a cis defect in vWF mRNA transcription or processing. In two type IIA vWD patients, two different but adjacent missense mutations were identified, the locations of which may identify an important vWF functional domain. Expression in heterologous cells of recombinant vWF containing one of these latter mutations reproduced the characteristic structural abnormality seen in type IIA vWD plasma.

Alleles↗
PubMed1987

Computerized tomography in hemophiliacs with head trauma.

Intracranial hemorrhage secondary to head trauma is a major cause of morbidity and mortality in patients with bleeding disorders. Indications for head computerized tomographic scanning (CT scan) on patients with bleeding disorders who sustain head trauma are not well established. We retrospectively reviewed the medical records and head CT scan results of 21 patients with bleeding disorders. Five patients had more than one episode of head trauma. The severity of head trauma per episode was classified according to objective clinical findings as minor in 12 episodes, moderate in 12, and severe in four. In three of four patients with severe head trauma, the CT scan showed evidence of intracranial hemorrhage. In this series, all 17 patients with 24 episodes of moderate or minor head trauma had normal head CT scans. We conclude that a larger prospective study is needed to further evaluate the diagnostic value of head CT scan in hemophilia patients with minor or moderate head trauma, as defined in this study.

Adolescent↗
PubMed1987

Reversal of central nervous system involvement in hemolytic uremic syndrome by use of plasma exchanges.

A 12-year-old girl presented with weakness, diplopia, and lethargy after a prodrome of gastroenteritis. Laboratory studies were compatible with a diagnosis of hemolytic uremic syndrome. She developed seizures that were controlled by diphenylhydantoin and valium. In spite of peritoneal dialysis and fresh frozen plasma infusions, she progressed to a left hemiplegia associated with a brain scan finding of decreased blood flow in the right middle cerebral artery perfusion area. A 5 liter whole blood exchange transfusion did not improve the neurological status or low platelet count. Daily plasma exchanges with fresh frozen plasma replacement resulted in normal platelet count within 48 hours and was followed by progressive improvement in neurological status. Platelet agglutinating factor decreased to control levels. A repeat brain scan was normal.

Antigens↗
PubMed1987

The effect of ABO blood group on the diagnosis of von Willebrand disease.

In order to firmly establish a normal range for von Willebrand factor antigen (vWF:Ag), we determined plasma vWF:Ag concentrations in 1,117 volunteer blood donors by quantitative immunoelectrophoresis. The presence of the ABO blood group has a significant influence on vWF:Ag values; individuals with blood group O had the lowest mean vWF:Ag level (74.8 U/dL), followed by group A (105.9 U/dL), then group B (116.9 U/dL), and finally group AB (123.3 U/dL). Multiple regression analysis revealed that age significantly correlated with vWF:Ag levels in each blood group. We then performed reverse ABO typing on stored plasma from 142 patients with the diagnosis of von Willebrand disease (vWd). Of 114 patients with type I vWd, blood group O was found in 88 (77%), group A in 21 (18%), group B in 5 (4%), and group AB in none (0%), whereas the frequency of these blood groups in the normal population is significantly different (45%, 45%, 7% and 3%, respectively) (P less than .001). Patients with type II or III vWd had ABO blood group frequencies that were not different from the expected distribution. There may be a subset of symptomatic vWd patients with decreased concentrations of structurally normal vWf (vWd, type I) on the basis of blood group O. Some individuals of blood group AB with a genetic defect of vWF may have the diagnosis overlooked because vWF levels are elevated due to blood type.

ABO Blood-Group System↗
PubMed1986

A naturally occurring, warm-reactive macroglobulin specific for papain-treated human platelets: preliminary characterization.

Sera from 28 of the 113 normal children and adults (25%) studied were found to contain an immunoglobulin capable of causing complement-dependent lysis of normal platelets treated with small quantities of papain. This factor reacts equally well at 4 degrees C and at 37 degrees C with a determinant induced on platelets from normal subjects by treatment with papain or bromelain, but not by trypsin, chymotrypsin, or neuraminidase. It does not bind to red cells treated with any of these enzymes. The site(s) for which the factor was specific could not be induced on platelets from six patients with type I Glanzmann's thrombasthenia (lacking glycoproteins IIb and IIIa), in contrast to platelets from each of 20 normal donors. Isolation and characterization of the factor has been difficult because of its intolerance to chemical and physical manipulation. In 11 of the 20 individuals studied, however, it was found to have the properties of an IgM immunoglobulin. The factor appears to be different from any previously described, naturally occurring human immunoglobulin. It has not yet been shown to be associated with any disease state, but in the presence of complement, it is capable of causing profound damage to platelets previously subjected to minimal proteolysis, and the possibility that it can provoke platelet destruction in some conditions deserves further study.

Adolescent↗
PubMed1986

HTLV-III serology in hemophilia: relationship with immunologic abnormalities.

We investigated the relationship of the presence of antibodies to HTLV-III and immunologic abnormalities in patients with hemophilia. Serum antibodies to HTLV-III were analyzed by ELISA assay, immunoprecipitation of labeled cell extracts, and immunoprecipitation of purified HTLV-III p24. Thirty-four (61%) of the total group (n = 56) had antibody to HTLV-III; 34 (76%) of 45 patients given commercial factor VIII preparations were seropositive, compared with none of 11 patients treated exclusively with cryoprecipitate obtained from volunteer blood donors. Of patients who were seropositive for HTLV-III antibody, 94% had abnormal T4/T8 ratios, and 33% of those whose serum was antibody negative had abnormal T4/T8 ratios; five patients, each antibody positive, have lymphadenopathy syndrome. Sequential studies in a subset of patients indicate that there is a changing pattern of antibody production to HTLV-III antigens after seroconversion.

Acquired Immunodeficiency Syndrome↗
PubMed1986

3,17 beta-Dihydroxy-20,21-epoxy-19-norpregna-1,3,5(10)-trienes: synthesis, rearrangement, cytotoxicity, and estrogen-receptor binding.

Diastereoisomers of 3,17 beta-dihydroxy-20,21-epoxy-19-norpregna-1,3,5(10)-triene have been prepared as potential antitumor agents. Both isomers undergo the base-catalyzed Payne rearrangement. The isomers were cytotoxic to mammalian cells in culture and were able to displace [3H]estradiol from binding sites in rat uterine cytosols with 1/7 and 1/70 the potency of estradiol. The reasons for this difference are discussed.

Animals↗