Search PubMed⌕ Search

Biomedical subjects

J C Gill

Publications and source records attributed to J C Gill.

53 records · Page 3Linked to original sources
PubMed1986

Loss of the largest von Willebrand factor multimers from the plasma of patients with congenital cardiac defects.

We identified a consecutive series of 12 children with noncyanotic congenital cardiac lesions with loss of the largest plasma von Willebrand factor (vWF) multimers determined by SDS-agarose electrophoresis. Seven had previous histories of mucocutaneous hemorrhage; ten had a prolonged bleeding time. Analysis of the factor VIII molecular complex revealed that six patients had reduced vWF measured both immunologically (vW:Ag) and by ristocetin cofactor assay (vW:rist). All had normal or borderline normal factor VIII procoagulant (F VIII) concentrations. Three children had prolonged partial thromboplastin times due to concurrent factor XII deficiency; none had laboratory evidence of intravascular coagulation. Five of the children were restudied after surgical correction of their cardiac lesions. Four had normalization of vWF multimers; the fifth, whose vWF was abnormal postoperatively, had a residual pressure gradient across a previous pulmonary artery banding site. Multimeric abnormalities were not found in the parents of three patients. Thus some patients with noncyanotic congenital heart disease may have an acquired abnormality of vWF that is normalized with correction of the abnormal hemodynamic state.

Blood Coagulation↗
PubMed1985

Persistence and progression of immunologic abnormalities in haemophilia.

Immunologic parameters in 51 patients with haemophilia treated with cryoprecipitate from volunteer donors or with commercial lyophilized concentrate were studied on 2-7 occasions. Concentrate users had significantly decreased mean T4 (helper)/T8 (suppressor) lymphocyte ratios when the initial (1.5 +/- .43) and most recent (1.25 +/- .60) values were compared (p less than .001), whereas in cryoprecipitate users mean values remained normal. Of the 22 concentrate users with initially normal T4/T8 ratios, 10 became abnormal during the study, an incidence of 45%. Fifteen of 28 (54%) patients with abnormal T4/T8 ratios had elevated circulating immune complexes (CIC), whereas all 16 patients with normal T4/T8 ratios had normal levels of CIC. Six patients have persistent lymphadenopathy.

Antigens, Surface↗
PubMed1985

Newborn haemostasis.

Although reliable haemostasis testing is difficult to obtain in the newborn infant, information gained from such testing is important to the diagnosis of hereditary and acquired haemostatic disorders. Newborn infants are at risk for developing haemorrhage or thrombosis when provoked by various pathological stimuli. Haemostasis screening tests and factor assays must be interpreted using gestational age-specific normal ranges. Frequently, the comparison of several factor assays provides the necessary information to diagnose and treat neonatal haemostatic abnormalities.

Blood Coagulation↗
PubMed1985

Long-term follow-up of hemophiliacs with lymphocytopenia or thrombocytopenia.

Immunologic abnormalities resembling those seen in patients with the acquired immunodeficiency syndrome (AIDS) are frequently observed in multitransfused but otherwise healthy individuals with hemophilia. To determine whether there was clinical or laboratory evidence to suggest an abnormality of immunoregulation in persons with hemophilia before the recognition of AIDS, we examined data collected by the Hemophilia Study Group from 1975 to 1979 on 1,551 patients with factor VIII deficiency. The prevalence of lymphocytopenia and thrombocytopenia in patients over 5 years of age on entry was found to be 9.3% (94/1,013) and 5.0% (26/518), respectively. These rates were significantly different from a normal population (P less than .00001 and less than .0003). No cases meeting the definition of AIDS were noted during the study. However, on follow-up in 1984 of a cohort of 79 patients with thrombocytopenia or lymphocytopenia on two or more occasions during the study, eight patients (10%) with AIDS-related abnormalities, including idiopathic thrombocytopenic purpura, non-Hodgkin's lymphoma, generalized lymphadenopathy, and oral moniliasis without obvious cause were identified. Of the 79 patients, liver disease accounted for five of the ten deaths (12.6% mortality) observed during a minimum follow-up of five years after detection of cytopenia. Only one death was attributed to bleeding in the absence of liver disease. We conclude that (a) the frequency of lymphocytopenia and thrombocytopenia was increased in multitransfused factor VIII-deficient hemophiliacs before the advent of AIDS, and (b) persistent lymphocytopenia and thrombocytopenia appear to be strongly associated with liver disease, which was the leading cause of death in a cohort of hemophiliacs followed five or more years.

Acute Kidney Injury↗
PubMed1983

Generalized lymphadenopathy and T cell abnormalities in hemophilia A.

Two patients with hemophilia A had generalized lymphadenopathy, lymphopenia, elevated IgG values, depressed T4 (helper) lymphocytes, elevated T8 (suppressor) lymphocytes, and abnormally low T4/T8 ratios. One of the patients, who also had hepatosplenomegaly, underwent cervical lymph node biopsy; the node contained 43% T8-lymphocytes, a marked elevation over the small fraction of T8 cells usually found in lymph nodes. These patients may have a form of the acquired immune deficiency syndrome described in male homosexuals, Haitians, intravenous drug abusers, and recently, in patients with hemophilia. We studied T cell phenotypes in 43 patients with hemophilia. Fourteen of 28 patients given commercial factor VIII concentrates had abnormal T4/T8 ratios; none of nine patients who used cryoprecipitate had abnormal values. T4 helper cells were significantly lower, T8 suppressor cells significantly elevated, and T4/T8 ratios significantly lower in the lyophilized concentrate users and in patients with hemophilia as a total group. The type of therapeutic factor VIII replacement may alter the risk of developing T4/T8 abnormalities or AIDS.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Prepooled cryoprecipitate for treatment of hemophilia A.

Lyophilized factor VIII concentrates, because of their convenience, are the most commonly used products for providing antihemophilic factor to patients with hemophilia A. Heightened concerns about associated complications indicate that cryoprecipitate usage will increase in the immediate future. We present a protocol for making cryoprecipitate more usable by "prepooling" individual units of cryoprecipitate in an "open" system. Our experience indicates this approach is safe, effective and acceptable to patients, including those on home therapy programs.

Factor VIII↗
PubMedDate not supplied

Mitogen responses and T4/T8 ratios in asymptomatic hemophiliac patients.

Lymphocyte responses to mitogen stimulation were studied in healthy hemophiliac patients. To study kinetics and dose response, three different concentrations of the mitogens phytohemagglutinin (PHA) and pokeweed mitogen (PWM) were used, and proliferation was measured on each of 6 days. Patients with T4/T8 ratios of less than 1.00 showed decreased proliferation compared to normal controls and to hemophiliac patients with ratios greater than 1.00. These findings were more pronounced with PWM than with PHA. Over the range of concentrations tested, patients and controls showed similar dose responses to PHA; no dose responses to PWM were demonstrable. There were no significant differences among the patient and control groups in kinetics of response to either mitogen. Interleukin-II (IL-2) activity produced in response to PHA stimulation also was studied. Hemophiliac patients with T4/T8 ratios less than 1.00 showed decreased IL-2 activity in 48-hour PHA culture supernatants compared to normal controls and hemophiliac patients with ratios greater than 1.00.

Adolescent↗
PubMedDate not supplied

Low-molecular-weight heparin in thrombotic disease in children and adolescents.

PURPOSE: The use of unfractionated heparin (UFH) in children is problematic. In adults, subcutaneous low-molecular-weight heparin (LMWH) is as effective as UFH in the treatment of thrombosis. Because pediatric data are limited, the authors studied the use of enoxaparin in children. PATIENTS AND METHODS: Nineteen children (ages 18 days to 19 years; median age, 40 months) with indications for thrombosis treatment or prophylaxis were studied. Six patients (median age, 33 months), treated on a protocol that included pharmacokinetic studies, initially received enoxaparin 1 mg/kg subcutaneously every 12 hours; doses then were adjusted until target plasma levels of 0.5 to 1.2 anti-Xa U/mL were achieved. The records of 13 additional patients treated with enoxaparin off study were reviewed. RESULTS: In the first six patients, enoxaparin pharmacokinetics was found to be similar to that in adults; once targeted levels were achieved, these remained stable. Among all 19 subjects, 14 had treatment of active thrombosis and 5 underwent thrombosis prophylaxis. For treatment of thrombosis, enoxaparin 1 mg/kg initially was administered subcutaneously every 12 hours. Target anti-Xa levels were achieved with 0.55 to 1.5 mg/kg every 12 hours (mean, 0.98 mg/kg; median, 1.0 mg/kg) in 1 to 7 days (median, 1 day). All patients in the treatment group had clinical improvement within 2 to 5 days, and 12 had follow-up radiological studies that confirmed this. For prophylaxis, enoxaparin was given at 1 mg/kg subcutaneously every 24 hours. No new thrombi were clinically evident in this group. There was no major bleeding with enoxaparin; one patient had transient mild mucosal oozing. CONCLUSION: In this limited population, enoxaparin seems to be a safe, effective, and convenient alternative to UFH in children and adolescents. The adult therapeutic target range of 0.5 to 1.2 anti-Xa U/mL is readily achievable with a starting dose of 1 mg/kg every 12 hours in most children. Initial close monitoring with plasma anti-Xa activity should be done and doses adjusted to achieve target range, particularly in neonates. In the population of this study, enoxaparin seems as effective as UFH in the period immediately thrombotic episode. These results should be confirmed in the ongoing randomized trial comparing LMWH with UFH in children.

Adolescent↗
PubMedDate not supplied

Failure of fresh frozen plasma infusions to alter the course of hemolytic uremic syndrome.

The hemolytic uremic syndrome (HUS) is characterized by thrombocytopenia, anemia, and acute renal failure. Fresh frozen plasma (FFP) infusions have been claimed to shorten the course of HUS. However, no long-term follow-up is available. Hence, we analyzed the effects of FFP infusions on acute resolution and long-term sequelae of HUS in 12 children (5 boys, 7 girls, mean age 4.5 years, range 7 months to 9 years) and compared to a historical control group of 31 children (13 boys, 18 girls, mean age 3 years, range 8 months to 9 years). The patient population, severity of HUS, and other modes of therapy except FFP were similar in the two groups. There was no statistically significant difference between the groups in the acute resolution of HUS as evaluated by recovery of anemia, thrombocytopenia, and return of renal functions. Long-term sequelae of HUS such as hypertension, end-stage renal disease, and CNS residual abnormalities were also similar in two groups. One child died in the FFP group and 2 children died in the control group. We feel that FFP infusions have no significant effect on the course of HUS and its use should be questioned.

Blood Transfusion↗