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Biomedical subjects

C T Kisker

Publications and source records attributed to C T Kisker.

At least 19 recordsLinked to original sources
PubMed2003

Prophylaxis in factor IX deficiency product and patient variation.

To determine the dosing needed to maintain a prophylactic level of factor IX (FIX) >/=2%, 15 non-inhibitor severe (</=1% FIX) deficient subjects participated in a double-blind, two-period crossover study to assess the pharmacokinetics of two FIX concentrates, Mononine (pd-FIX), an ultra-high-purity plasma-derived concentrate, and BeneFix (r-FIX), a recombinant product. The median recovery in the pd-FIX group was 1.67 IU dL(-1) per IU kg-1+/-1.07 vs. 0.86 IU dL(-1) per IU kg(-1)+/-0.32 in the r-FIX group (P = 0.0002). The median half-life for pd-FIX was 12.9 +/-1.7 h compared with 13.7 +/- 2.9 h for r-FIX (P = 0.016). Fitted dose activity curves were computer-simulated to depict multiple-dose activity curves for each patient with each product that would maintain prophylactic levels of >/=2%. Based on pharmacokinetic analysis the median amount of concentrate needed to maintain a prophylactic level >/=2% for 30 days when administered every third day is 677 IU kg(-1) pd-FIX (range 388-6005 IU kg(-1) pd-FIX) compared with 1168 IU kg(-1) r-FIX (range 268-13085 IU kg(-1) r-FIX). The median cost for 30 days of prophylaxis of an average 25-kg 8-year-old child at the current University of Iowa Price (0.87 US dollars Mononine/0.86 US dollars BeneFix as of December 2002) if given every third day would be 19,972 US dollars and 34,456 US dollars for r-FIX. However, because of wide inter-patient variability in recovery and half-life, pharmacokinetic evaluation of each patient is necessary to determine the appropriate dosing schedule and product best suited for prophylaxis.

Adolescent↗
PubMed2000

Incidence of focal white matter lesions in a population of hemophiliac children and their normal siblings. Hemophilia Growth and Development Study.

OBJECTIVE: This analysis was undertaken to evaluate the etiology and sequelae of 2- to 5-mm focal white matter hyperintensities on T2-weighted MR images of some participants enrolled in the Hemophilia Growth and Development Study (HGDS). MATERIALS AND METHODS: The HGDS is a multicenter study of the growth and development, neurological, neuropsychological, and immune functioning of a cohort of children and adolescents, 62% of whom were infected with HIV through the use of clotting factor concentrates, and their non-hemophiliac, non-HIV infected male siblings. The current investigation was conducted with all three groups of HGDS participants: HIV-positive hemophiliacs (n = 207), HIV-negative hemophiliacs (n = 126), and their siblings (n = 47). Magnetic resonance imaging was performed at each center, with a variety of 0.3 to 1.5 T instruments. Standard examinations included 5-mm-thick T1-weighted sagittal and axial images, intermediate, and T2-weighted axial images. A study of abnormalities of the coagulation system known to be associated with thrombotic events was conducted among a subgroup of participants (n = 51) from eight centers. RESULTS: Lesions were not associated with hemophilia-related factors, immune function, hematologic, or neurologic factors. There were no associations between the presence of white matter lesions and defects of coagulation in any of the assays completed. CONCLUSION: The 2- to 5-mm focal white matter hyperintensities on T2-weighted MR images of the brain were incidental findings in our study population.

Adolescent↗
PubMed2000

Human coagulation factor FVIIa (recombinant) in the management of limb-threatening bleeds unresponsive to alternative therapies: results from the NovoSeven emergency-use programme in patients with severe haemophilia or with acquired inhibitors.

This open-label, emergency-use study evaluated the efficacy and safety of activated human coagulation factor VIIa (recombinant) (rFVIIa) (NovoSeven; Novo Nordisk Pharmaceuticals, Inc., New Jersey, USA) in treating limb-threatening joint or muscle bleeds in 17 patients with haemophilia A or B and six patients with acquired inhibitors to factor VIII or factor IX. All patients had previously failed on one or more alternative therapies. rFVIIa administration was effective or partially effective in controlling joint or muscle bleeds in 34 out of 35 (97%) bleeding episodes; in 23 patients, 14 of 17 (82%) muscle bleeds and 16 of 18 (89%) joint bleeds were effectively controlled. These findings suggest that rFVIIa is an effective and well-tolerated therapeutic option in the management of joint or muscle haemorrhage in patients with haemophilia and in patients with acquired inhibitors.

Adolescent↗
PubMed1999

Changes in hepatitis B serologic titers in HIV+ and HIV- children with haemophilia.

This longitudinal study examines differences in hepatitis B immune titres in children and adolescents with haemophilia to determine if they are dependent on how immunity was acquired (vaccination or natural infection), and whether they are related to the child's HIV status and/or are influenced by HIV disease progression. Serologic titres (HBcAb, HBsAb) and HBsAg were measured prospectively at baseline, and at years 1, 2 and 3 of follow-up in 126 HIV- and 207 HIV+ children and adolescents with haemophilia. Analyses were performed to assess the impact of HIV status on the measured titres, and for HIV+ subjects to examine the association with CD4+ lymphocyte counts and p24 antigen status. The results show that HIV+ children were more likely than HIV- children to lose vaccine-induced immunity as indicated by the loss of HBsAb. There was an increased risk of losing HBsAb with higher CD4+ counts and younger age. Re-immunization was not successful in seven of eight HIV+ children. Two subjects (one HIV+, one HIV-) entered the study HBsAg- but became HBsAg+ over the course of follow-up. Seven HIV+ subjects lost natural immunity as indicated by the loss of HBcAb. The loss of either HBsAb or HBcAb in HIV--subjects was negligible to absent. In conclusion, because of the loss of immunity in HIV+ children the viral safety of factor replacement concentrates for these children is an important consideration. HIV- children rarely lose immunity, therefore frequent measures of HBsAb are not necessary.

CD4 Lymphocyte Count↗
PubMed1998

Home treatment of mild to moderate bleeding episodes using recombinant factor VIIa (Novoseven) in haemophiliacs with inhibitors.

OBJECTIVE: To assess the safety and efficacy of a fixed dose of recombinant activated factor VII (rFVIIa; NovoSeven) in the home setting for mild to moderately severe joint, muscle; and mucocutaneous bleeding episodes in patients with haemophilia A or B with inhibitors. DESIGN: Multicentre, open-label, single arm, phase III study of one year duration. METHODS; Patients or their caregivers administered up to three doses of rFVIIa (90 microg/kg i.v.) at 3 h intervals within 8 h of the onset of a mild to moderate bleeding episode. Once the subject considered that rFVIIa had been "effective" with regard to haemostasis (after 1-3 injections), one further (maintenance) dose of rFVIIa was administered. RESULTS: Of 60 patients enrolled, 56 experienced at least one bleed, and 46 completed the one year study. 614 of 877 bleeds (70%) were evaluable according to protocol definitions. Haemostasis was rated as "effective" in 92% (566/614) of evaluable bleeds after a mean of 2.2 injections. For successfully treated episodes, the time from onset of bleeding until administration of the first injection was 1.1+/-2.0 h (mean+/-SD). Twenty-four hours after initial successful response, haemostasis was reported as having been maintained in 95% of cases. Efficacy was comparable for muscle, joint and target joint, and mucocutaneous bleeding episodes. In an intent-to-treat analysis of all 877 bleeding events, efficacy outcomes were equivalent to the evaluable bleeds, with an effective response in 88% of treated episodes. Treatment-related adverse events occurred in 32 (3% of all) bleeding episodes and consisted of re-bleeds/new bleeds in more than 50% (18/32) of these events. A single episode of superficial thrombophlebitis was the only thrombotic complication encountered, and there were no patient withdrawals due to adverse events. Development of FVII(a) antibodies could not be detected, and hypersensitivity reactions to rFVIIa were not reported. CONCLUSION: rFVIIa is effective and well tolerated when used in the home setting to treat mild to moderate bleeding episodes in patients with haemophilia A or B with inhibitors.

Adolescent↗
PubMed1997

Shared management of children with cancer.

OBJECTIVE: To determine the risks and benefits of university-based pediatric oncologists and community-based primary care physicians sharing the management of children with cancer. DESIGN: Physicians participating in shared management of children with cancer were surveyed, and the outcomes of the children were measured. SETTING AND PARTICIPANTS: One hundred thirty-seven community-based primary care physicians participated in the management of the 226 children with cancer in Iowa and western Illinois during the past 15 years. The survival of the 226 children was compared with that of 240 randomly selected children treated using the identical treatment protocols but treated only by pediatric oncologists. INTERVENTION: A 7-point Likert scale questionnaire was completed by 97 (71%) of the participating primary care physicians. RESULTS AND OUTCOME MEASURES: There were no differences in the survival of children using shared management compared with those treated only by pediatric oncologists. Primary care physicians believed that shared management is of economic and psychosocial benefit to patients, improves the treatment choices available to patients, does not require excessive time, and does not result in loss of practice income. The system strengthens the primary care physicians' relationships with oncologists and results in additional referrals to the university-based pediatric oncologists. It is of educational value, is personally satisfying, and provides relief from the stress associated with caring for these families. Primary care physicians would like to see this system expanded to include other children with special health care needs. CONCLUSION: The shared-management approach to care is a viable attractive option of health care provision for children.

Attitude of Health Personnel↗
PubMed1997

Treatment of nonmetastatic osteosarcoma of the extremity with preoperative and postoperative chemotherapy: a report from the Children's Cancer Group.

PURPOSE: The specific aims of this study were to improve event-free survival (EFS) in patients with newly diagnosed nonmetastatic osteosarcoma of an extremity using the histologic response to neoadjuvant chemotherapy to determine postoperative chemotherapy; to evaluate a uniform histologic grading system that measures tumor response; and to identify patient characteristics that might influence EFS and survival. PATIENTS AND METHODS: Two hundred sixty-eight patients with nonmetastatic osteosarcoma of the extremity were entered between August 1983 and October 1986. Preoperative chemotherapy consisted of four courses of high-dose methotrexate (MTX) and one course of bleomycin, cyclophosphamide, and dactinomycin (BCD). Histologic response to preoperative chemotherapy was determined by morphometric analysis. Good histologic responders (< 5% residual viable tumor) were treated postoperatively with MTX, BCD, and doxorubicin (DOX); poor histologic responders were treated with BCD, DOX, and cisplatin (CDDP). RESULTS: The 8-year EFS and survival rates were 53% and 60%, respectively. Two hundred six patients had their tumors assessed for histologic response: 28% displayed a good histologic response to preoperative chemotherapy. Good histologic responders had an 8-year postoperative EFS rate of 81% and survival rate of 87%; those with a poor histologic response had an 8-year postoperative EFS rate of 46% and survival rate of 52%. A primary tumor site in the proximal humerus or proximal femur and an elevated serum alkaline phosphatase level were associated with an increased risk of an adverse event, whereas the type of surgical procedure was not. CONCLUSION: EFS and survival appear to be directly related to histologic response to neoadjuvant chemotherapy.

Adolescent↗
PubMed1996

AIDS-associated non-Hodgkin's lymphomas as primary and secondary AIDS diagnoses in hemophiliacs. Hemophilia Malignancy Study Group.

We studied the characteristics and temporal trends of AIDS- associated non-Hodgkin's lymphoma (AIDS-NHL) in individuals with hemophilia. Prospective data were collected on 33 HIV-positive hemophiliacs with AIDS-NHL enrolled in the Hemophilia Malignancy Study (HMS), of whom 21 had primary and 12 had secondary or subsequent AIDS-defining illnesses, and analyzed for frequency and temporal trends. As compared with primary AIDS- NHL, secondary AIDS-NHL occurred at an older mean age, 37 versus 29 years (p = 0.12); at a lower mean CD4 count, 46 versus 154 (p = 0.07); after a longer period of immunosuppression (CD4 < 200/microl), 41 versus 16 months (p = 0.03); and with shorter median survival, 2 versus 7 months (p = 0.09). The presence of EBV in tumor tissue was associated with shorter survival, 1 versus 7 months (p = 0.17). Between 1981 and 1988 and 1989 and 1994, the proportion of primary AIDS diagnoses that were AIDS-NHL changed minimally, 4.6 versus 6.1%, whereas there were significant decreases in Pneumocystis carinii pneumonia (PCP, p = 0.02) and wasting (p = 0.07), and an increase in Candida (p = 0.004). These findings confirm that an increasing proportion of AIDS-NHL in hemophiliacs are occurring as secondary or later AIDS diagnoses, and they are associated with prolonged duration of immunosuppression.

AIDS-Related Opportunistic Infections↗
PubMed1995

Effect of hyperinsulinemia on the development of blood coagulation in the lamb fetus.

Infants of diabetic mothers have an increased risk for thrombosis. The etiology of their hypercoagulable state is unknown. To examine the effects of hyperinsulinemia on the development of coagulation during fetal life, 10 sets of chronically catheterized fetal lambs were studied. One twin from each pair of 120-d gestation lamb fetuses was infused with insulin at a rate of 2.5 U/h for 48 h, whereas its twin sibling was infused with an equal volume (20 mL) of dextrose 5% in water. Changes in coagulation factor activities were measured before and after the infusions, and differences were analyzed by paired t tests. There was a significant decrease in protein C after insulin treatment in the insulin-treated twins. There were relative increases in fibrinogen factors V, VII, and XI when the insulin-treated group was compared with the controls. The changes are consistent with an increased risk of thrombosis and may explain, in part, the higher incidence of thrombosis in infants of diabetic mothers.

Animals↗
PubMed1993

Acquired immunodeficiency syndrome-associated non-Hodgkin's lymphomas and other malignancies in patients with hemophilia.

Non-Hodgkin's lymphoma (NHL) is the most common human immunodeficiency virus (HIV)-associated malignancy in hemophiliacs. We studied the incidence and clinicopathologic features of NHL in 3,041 hemophiliacs followed at 18 US Hemophilia Centers between 1978 and 1989. Of the 1,295 (56.6%) who were HIV(+), 253 (19.5%) developed acquired immunodeficiency syndrome (AIDS), of whom 14 (5.5%) developed NHL. Three NHL occurred in HIV(-) hemophiliacs, for a 36.5-fold greater risk in HIV(+) than HIV(-) hemophiliacs (P < .001). The NHL incidence rate was 29-fold greater than in the US population by Surveillance, Epidemiology, and End Results (SEER) estimates (P < .001). Between 0 and 4 lymphomas have been observed per year between 1978 and 1989. At presentation 13 (92.9%) of the HIV(+) NHL were extranodal. Ten were stage IV, 1 stage II, and 3 stage IE. Ten (71.4%) were high-grade, 3 (21.4%) intermediate-grade, and 1 (7.1%) was a low-grade B-cell lymphoma. Epstein-Barr virus (EBV) DNA was detected in 36% by in situ hybridization, including one central nervous system (CNS) lymphoma. The mean CD4 cell count at NHL diagnosis was 64/mm3, the mean latency from initial HIV infection was estimated to be 59 months, and the median survival was 7 months. The incidence of basal cell carcinoma in HIV(+) hemophiliacs was 18.3-fold greater than in HIV(-) hemophiliacs (P < .001) and 11.4-fold greater than in the US population (P < .001). In conclusion, incidence rates of NHL and basal cell carcinoma in HIV(+) hemophiliacs are significantly increased over rates in HIV(-) hemophiliacs and over rates in the US population. Clinicopathologic presentation of NHL in HIV(+) hemophiliacs is similar to that in HIV(+) homosexual men.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Thyroxine and fetal blood coagulation: a fetal lamb study.

Glucocorticoids have been shown to accelerate the development of blood coagulation in the fetal lamb (Kisker, Robillard & Bohlken, 1983). The current studies examine the influence of high levels of triiodothyronine (T3) on the development of blood coagulation in the fetal lamb. Eight twin fetal lambs were studied during the last trimester of pregnancy (109-138 days gestation) using chronically placed arterial and venous catheters for infusion of T3 and withdrawal of blood samples. One fetus of each twin was infused intravenously with T3 at a constant rate of 0.6 micrograms T3/0.4 ml/h for 48 h. The other twin was infused with 5% dextrose at 0.4 ml/h for 48 h. Blood samples for measuring PT, PTT, TT, fibrinogen, factors II, V, VII, VIII, IX, X, XI and XII were obtained prior to and at the completion of the infusions. The results were analyzed for differences between the samples from paired control and T3 treated animals. Factor V significantly decreased in the T3 infused animals from 51.2% +/- 12.5% to 44.8% +/- 13.8% (P = 0.038). Factor VII also decreased in the treated animals 57.8% +/- 20% to 43.6% +/- 10.8%, but the changes were not statistically significant (P = 0.06). Factor XII significantly increased in the treated animals from 37% +/- 10.5% to 45% +/- 13.7% (P = 0.004). High levels of T3 in third trimester fetal lambs are accompanied by a moderate decrease in factor V and an increase in factor XII activity.

Animals↗
PubMed1991

Negative regulation of angiotensinogen gene expression by glucocorticoids in fetal sheep liver.

The effect of glucocorticoids in regulating liver angiotensinogen gene expression was studied in chronically instrumented fetal sheep during the last trimester of gestation and was compared with the expression of other hepatic genes (prothrombin, factor IX, and albumin). Four sets of twins were studied at 118 d of gestation, and three sets were studied at 138 d of gestation (term, 145 d). One of each set of twins was infused intraperitoneally with cortisol (5 mumol.mL-1.h-1) for 48 h, whereas the other twin received the same volume (1 mL/h) of normal saline. Plasma cortisol concentration increased from 0.32 +/- 0.12 and 2.7 +/- 0.12 nmol/100 mL to 44.2 +/- 20.0 and 37.7 +/- 8.2 nmol/100 mL in 118- and 138-d fetuses, respectively, during the cortisol infusion; no changes were observed in fetuses infused with saline alone. At the end of the infusion period, the animals were anesthetized, the fetal liver was removed, and total cellular RNA was isolated and probed for angiotensinogen, prothrombin, factor IX, and albumin. The results demonstrated that cortisol infusion decreased angiotensinogen mRNA by 61% in 138-d fetuses and albumin mRNA expression by 2.4-fold in 118-d fetuses and by 3.4-fold in 138-d fetuses. On the other hand, cortisol had no effect on fetal factor IX gene expression but increased prothrombin mRNA levels by 65% in 118-d fetuses and 62% in 138-d fetuses. Taken together, our results suggest that, during fetal life, angiotensinogen gene expression is negatively regulated by glucocorticoids. This effect is not universal because cortisol increases fetal prothrombin gene expression.

Angiotensinogen↗
PubMed1988

Measurement of prothrombin mRNA during gestation and early neonatal development.

Prothrombin levels in the fetal and newborn lamb follow a gestational age-related pattern of development. The changes in activity are reflected by similar changes in prothrombin antigen concentration. Our investigations indicate that these changes in prothrombin antigen and activity levels are paralleled by changes in the levels of prothrombin messenger RNA present in liver samples from fetuses of various gestational ages.

Animals↗
PubMed1987

The animal models for hemorrhage and thrombosis in the neonate.

Animal models have added significantly to our understanding of adult hemorrhagic and thrombotic diseases. Few models, however, have been developed for studies of the hemostatic disorders in the fetus and newborn. This report reviews the current information on animal models of fetal and neonatal hemostasis. The requirements of a relevant model are addressed and previous studies using fetal and neonatal animal models are reviewed. A recommendation of a single animal for all studies of fetal and neonatal hemostasis is not possible. However, the lamb has been the most frequently studied and appears to provide relevant information regarding normal development and the factors which may adversely influence hemostasis in the fetus and newborn. Animal models, in contrast to in vitro experiments, provide a means of studying the entire spectrum of biologic consequences that results from a single experimentally induced alteration. In the "Introduction to the Study of Experimental Medicine" Claude Bernard commented "I not only conclude that experiments made on animals from the physiological, pathological, and therapeutic points of view have results that are applicable to theoretic medicine, but I think that without such comparative study of animals, practical medicine can never acquire a scientific character". In the area of blood coagulation, animal models have added significantly to our understanding of the pathophysiology of hemorrhage and thrombosis. There are animal models for both congenital and acquired bleeding disorders including factor VII, VIII, IX, X, XI, and fibrinogen deficiency; as well as von Willebrand's disease and disorders of platelet function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Effect of metabolic acidosis on fetal renal haemodynamics.

The effects of metabolic acidosis on renal haemodynamics and intrarenal blood flow distribution was studied in two groups of chronically-catheterized fetal sheep between 122 and 130 days of gestation. One group (experimental group) was studied before and during infusion of 1.1 M lactic acid, whereas the second group received on infusion of dextrose 5% (w/v) in water and served as a time-control group. Infusion of lactic acid for 2 h decreased fetal arterial pH from 7.37 +/- 0.01 to 6.95 +/- 0.02, did not change arterial blood pressure, but produced a significant decrease in renal blood flow (41 +/- 3 to 33 +/- 7 ml/min, P less than 0.05) and a significant increase in renal vascular resistance (1.42 +/- 0.13 to 1.86 +/- 0.18 mmHg/ml/min, P less than 0.05). Moreover, a significant decline in cortical blood flow was also observed in the outer portion of the renal cortex during lactic acidosis. Taken together, these results suggest that metabolic acidosis produces significant changes in fetal renal haemodynamics not associated with changes in arterial blood pressure.

Acidosis↗
PubMed1986

Hepatic imaging in stage IV-S neuroblastoma.

Stage IV-S neuroblastoma describes a group of infants with tumor spread limited to liver, skin, or bone marrow. Such patients, who constitute about 25% of affected infants with neuroblastoma, may expect spontaneous tumor remission. We report 18 infants with Stage IV-S neuroblastoma, 83% of whom had liver involvement. Imaging investigations included Technetium 99m sulfur colloid scan, ultrasound, and CT. Two patterns of liver metastasis were noted: ill-defined nodules or diffuse tumor throughout the liver. Distinction of normal and abnormal liver with diffuse type metastasis could be quite difficult, particularly with liver scans. We conclude that patients with Stage IV-S neuroblastoma have ultrasound or CT examination as an initial workup, with nuclear medicine scans reserved for followup studies.

Adrenal Gland Neoplasms↗