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Biomedical subjects

C Kaplan

Publications and source records attributed to C Kaplan.

At least 37 records · Page 2Linked to original sources
PubMed2001

A naturally occurring point mutation in the beta3 integrin MIDAS-like domain affects differently alphavbeta3 and alphaIIIbbeta3 receptor function.

We have investigated the effect of a new Leu196Pro mutation, identified in the MIDAS-like domain of the beta3 integrin subunit in a patient with type II Glanzmann thrombasthenia, on beta3 integrin receptor function. Expression of the mutant beta3Pro196 subunit in CHO cells, either associated with recombinant human alphaIIb or alphav, resulted in normal biosynthesis of beta3 and heterodimerization with alphav or alphaIIb, but selectively interfered with alphaIIbbeta3 maturation and transport to the cell surface. Functional analysis of the beta3 mutant receptors revealed strong inhibition of alphavbeta3-mediated cell spreading on immobilized fibrinogen, focal contact formation, p125FAK phosphorylation and fibrin clot retraction, as opposed to normal alphaIIbbeta3-mediated cell interaction with immobilized fibrinogen, focal contact translocation and signaling. In contrast, antibody- or DTT-activated mutant aIIbbeta3 was unable to bind soluble fibrinogen or the ligand mimetic PAC-1 monoclonal antibody, but underwent a conformational change following RGD peptide binding as demonstrated by AP5-LIBS epitope expression. These results suggest that (1) the highly conserved TL196T motif in the beta3 integrin subunit is located in a domain structurally important for the exposure of a functional binding site for soluble fibrinogen; and (2) that the MIDAS-like contact site in beta3 is not involved in alphaIIbbeta3-mediated cell adhesion to immobilized fibrinogen, while it is essential for alphavbeta3-mediated interaction with this ligand.

Amino Acid Sequence↗
PubMed2000

Autoantibodies against platelet glycoproteins in critically ill patients with thrombocytopenia.

PURPOSE: The aim of the study was to investigate immunologic causes of thrombocytopenia in critically ill patients, especially causes that were related to platelet-associated IgG antibodies. SUBJECTS AND METHODS: All patients admitted to two intensive care units between May 1 and October 30, 1997, who developed thrombocytopenia (less than 100 x 10(9) platelets/L) were studied prospectively. We measured platelet-associated IgG with a radioimmunoassay using I(125)-labeled polyclonal antihuman IgG. Characterization of platelet-associated IgG was assessed with a monoclonal antibody immobilization of platelet antigen. Circulating immune complexes were also assayed. RESULTS: Of the 61 patients with thrombocytopenia, elevated platelet-associated IgG was found in 18 (30%). Associated antiplatelet autoantibodies (glycoprotein IIb/IIIa) were detected in 4 patients, circulating autoantibodies (glycoprotein Ib/IX) were detected in sera from 2 patients, and circulating immune complexes were detected in 3 patients. The nature of the platelet-associated IgG could not be determined in 10 patients. Elevated platelet-associated IgG was associated with sepsis and previous cardiopulmonary bypass. Thrombocytopenic patients with elevated platelet-associated IgG had a lower nadir platelet count (58 +/- 27 x 10(9)/L vs 74 +/- 24 x 10(9)/L, P = 0.03). CONCLUSION: Elevated platelet-associated IgG, some of which are platelet autoantibodies, is frequent in thrombocytopenic patients with sepsis or after cardiopulmonary bypass.

Adult↗
PubMed2000

The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations.

OBJECTIVES: This study evaluated the prevalence and severity of anemia in patients with congestive heart failure (CHF) and the effect of its correction on cardiac and renal function and hospitalization. BACKGROUND: The prevalence and significance of mild anemia in patients with CHF is uncertain, and the role of erythropoietin with intravenous iron supplementation in treating this anemia is unknown. METHODS: In a retrospective study, the records of the 142 patients in our CHF clinic were reviewed to find the prevalence and severity of anemia (hemoglobin [Hb] <12 g). In an intervention study, 26 of these patients, despite maximally tolerated therapy of CHF for at least six months, still had had severe CHF and were also anemic. They were treated with subcutaneous erythropoietin and intravenous iron sufficient to increase the Hb to 12 g%. The doses of the CHF medications, except for diuretics, were not changed during the intervention period. RESULTS: The prevalence of anemia in the 142 patients increased with the severity of CHF, reaching 79.1% in those with New York Heart Association class IV. In the intervention study, the anemia of the 26 patients was treated for a mean of 7.2 +/- 5.5 months. The mean Hb level and mean left ventricular ejection fraction increased significantly. The mean number of hospitalizations fell by 91.9% compared with a similar period before the study. The New York Heart Association class fell significantly, as did the doses of oral and intravenous furosemide. The rate of fall of the glomerular filtration rate slowed with the treatment. CONCLUSIONS: Anemia is very common in CHF and its successful treatment is associated with a significant improvement in cardiac function, functional class, renal function and in a marked fall in the need for diuretics and hospitalization.

Aged↗
PubMed2000

Understanding suicide attempts by adolescent Hispanic females.

This article presents integrative model to aid clinicians in understanding suicide attempts by adolescent Hispanic females. On the basis of knowledge accumulated through clinical and research experience, the model describes a convergence of sociocultural, familial, developmental, and psychological factors that include considerations of family and parental functioning; adolescent female development; and the relationships of fathers, mothers, and daughters.

Adolescent↗
PubMed2000

[Materno-fetal platelet allo-immunization revealed by in utero intracerebral fetal hemorrhage: proposed management for the next pregnancy].

Materno-fetal platelet allo-immunization causes fetal or neonatal thrombocytopenia and sometimes severe intracerebral bleeding. The HPA-1s antigen is most generally implicated. This accident can occur during the first pregnancy with a major risk of severe recurrence during the next pregnancy. These women require specific care in a specialized center although no consensus has been reached on management of second pregnancies. Proposed treatments include immunoglobulins and/or corticosteroids, fetal blood puncture and unique or iterative platelet transfusions.

Abortion, Therapeutic↗
PubMed2000

Sporadic fatal insomnia: a case study.

A 58-year-old man died after a 27-month illness characterized by insomnia, confirmed by polysomnography. He was homozygous for methionine at codon 129 of the prion gene but had no mutation in the prion gene. Neuropathology showed thalamic and olivary atrophy and no spongiform changes. Paraffin-embedded tissue blotting demonstrated abnormal prion protein in the brain. This is the first case of the sporadic form of fatal familial insomnia with demonstration of the disorder by polysomnography.

Humans↗
PubMed1999

Gene frequencies of human platelet antigens in the Tunisian population.

Gene frequencies for the human platelet antigens HPA-1, -3 and -5 in the Tunisian population were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on 93 volunteer blood donors (78 were tested for HPA-1, 90 for HPA-3 and 93 for HPA-5). This study shows the highest frequencies of the HPA-1b (0.25) and HPA-5b (0.22) yet recorded. These antigens are considered as markers of a high risk of platelet alloimmunisation in other populations, and for this reason particular attention should be paid in the case of pregnancy or blood transfusion in this population. The 9 base pair deletion located in intron 21 of the GPIIb gene associated with HPA-3b determinant is present in this population. No individual showed the polymorphism associated with HPA-1b (T-->G at codon 40 of the GPIIIa).

Antigens, Human Platelet↗
PubMed1999

Pregnancy-associated autoimmune neonatal thrombocytopenia: role of maternal HLA genotype.

In a prospective study between 1993 and 1998, data was collected from 46 pregnant women and subsequently from their babies. 25 pregnant women with active autoimmune thrombocytopenic purpura (AITP) or a history of AITP (group A) and 21 pregnant women with isolated thrombocytopenia and identification of specific platelet autoantibodies detected by monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay (group B) were evaluated for platelet-associated immunoglobulin-G (PAIgG), MAIPA assay and HLA genotype. Neonatal platelet counts were performed at least three times in the first week. 11 neonates were thrombocytopenic (23.9%). No severe haemorrhage occurred. There were no significant differences regarding the values of PAIgG or positive MAIPA tests between mothers of thrombocytopenic or healthy newborns. A significant difference, however, regarding the HLA DRB3* allele was found, with a high incidence in the subgroup of mothers of healthy newborns (P = 0.005). A similar trend was found among mothers with anti-GPIIbIIIa antibodies (P = 0.06). In contrast, HLA DRB5* allele appeared to be present especially in mothers of thrombocytopenic newborns (not significant). Our data suggest that mothers with AITP who have the HLA DRB3* genotype are unlikely to give birth to a thrombocytopenic baby. This study provides a preliminary report on a noninvasive test to identify infants who are likely to be affected.

Autoantibodies↗
PubMed1999

The medical expert witness: time to regulate conflicts of interest.

Doctors are often asked to provide expert evidence for the courts. Whilst there is a considerable body of work in the legal literature, there is relatively little discussion and guidance in general medical literature. This is important as more doctors are drawn into the legal arena, and their ability to assist the court is a matter of consequence. The potential adverse effects in terms of the human, psychological and financial costs to the litigant parties, and the speed of access to justice, are considerable if the work is not done properly. Possible solutions to the present system are discussed and a set of guiding principles for acting as an expert witness is proposed.

Adult↗
PubMed1999

Early life family disadvantages and major depression in adulthood.

BACKGROUND: There is evidence that exposure to social and family disadvantages in childhood are a risk factor for adult depression. AIMS: To explore the effects of multiple adversity in early childhood on adult depression, and the relative effects of the different adversities. METHOD: This study utilises data from the Newcastle Thousand Family Study. Information on childhood disadvantages was collected when the participants were 5 years old, and information on mental health was gathered when they were 33 years old. Mental health data were scrutinised blind to the evidence of early disadvantage, and best-estimate diagnoses of major depressive disorder were made according to DSM-III-R criteria. RESULTS: Multiple family disadvantages in childhood substantially increase the risk of suffering a major depressive disorder in adulthood. Such disadvantages include family or marital relationship instability, a combination of poor mothering and poor physical care, and a combination of dependence on social welfare and overcrowding. For females major depression was linked in particular to the quality of parenting in early life. CONCLUSIONS: Social and family (especially multiple family) disadvantages during childhood predispose individuals to an increased risk of major depression in adulthood.

Adult↗
PubMed1998

Pregnancy-associated thrombocytopenia revisited: assessment and follow-up of 50 cases.

Thrombocytopenia detected during pregnancy addresses the issue of its mechanism and of the possible occurrence of neonatal thrombocytopenia. To further investigate these issues, 50 women referred to us because of thrombocytopenia detected during pregnancy (platelet count, <150 x 10(9)/L), were extensively studied, as well as their offspring. Among these thrombocytopenic women, we used the threshold of 70 x 10(9)/L to differentiate between mild and severe thrombocytopenia. Whatever the severity of thrombocytopenia, we found biological features of an autoimmune disorder in 48% of the women, and chronic thrombocytopenia in 55%. A familial thrombocytopenia was evidenced in 1 case. These 50 women gave birth to 63 neonates, among whom 24 were thrombocytopenic, either at birth or during the first week of life. Neonatal thrombocytopenia could only be predicted in multiparous women, on the basis of previous neonatal thrombocytopenia in older siblings, and/or when maternal platelet life span study, performed before pregnancy, had evidenced an autoimmune thrombocytopenia (AITP)-like profile. These results suggest that, in case of pregnancy-associated thrombocytopenia, familial and immunological studies, combined with postdelivery iterative platelet counts, should be performed to properly characterize the thrombocytopenia. Moreover, the platelet count of the neonate should be carefully assessed at birth and during the following days, a platelet life span study should be performed after delivery in the mother, because these two parameters are likely to bring valuable information regarding the forthcoming pregnancies and the risk of neonatal thrombocytopenia.

Autoantibodies↗
PubMed1998

Pharmacokinetics and pharmacodynamics of CI-992 following intravenous and oral administration to cynomolgus monkeys.

The purpose of this study was to characterize CI-992 pharmacokinetics and pharmacokinetics/pharmacodynamics (PK/PD) in sodium deplete monkeys. Panels of monkeys were administered CI-992 as a 1 h intravenous infusions (0.1 and 1 mg kg-1) or as single oral doses (0, 10, 50, and 100 mg kg-1). Mean arterial blood pressure (MABP) was monitored and serial blood samples were collected up to 24 h postdose. Plasma CI-992 concentrations were quantitated by radioimmunoassay. Pharmacokinetic parameters were calculated by noncompartmental methods. PK/PD relationships were assessed by standard methods. Oral bioavailability of CI-992 in the monkeys was < 2%; steady-state volume of distribution was 0.67 L kg-1; clearance was 10.4 mL min-1 kg-1. Following oral administration, tmax generally occurred 6-9 h postadministration; plasma CI-992 concentrations increased with increasing dose between 10 and 50 mg kg-1, but did not change appreciably from 50 to 100 mg kg-1. After intravenous administration, change in MABP was correlated with plasma CI-992 concentration through an effect compartment model in which the maximum achievable effect was a 22 mm Hg decrease in MABP; the steady-state concentration which produced half the maximum effect was 11 ng mL-1. Following the 10 mg kg-1 oral dose the maximum decrease in MABP was 19.1 mm Hg; higher doses did not produce greater maximum response but increased the duration of action. In contrast to observations following intravenous administration, a trend for decreasing MABP with increasing plasma CI-992 was not apparent following oral CI-992 administration.

Administration, Oral↗
PubMed1998

Low frequency of HLA-B27 and scarcity of ankylosing spondylitis in a Zairean Bantu population.

Ankylosing spondylitis (AS) is an inflammatory rheumatic disease which is thought to be rarely seen in African Blacks. Its genetic predisposition has been stressed in Caucasians where the HLA-B27 antigen is firmly linked to the disease. In the present study, HLA-B27 antigen was determined in 146 individuals of Bantu root. Only one of these subjects was found to possess HLA-B27 antigen. This study correlates the low frequency of HLA-B27 with the observed scarcity of AS in patients attending a clinic in Kinshasa for osteoarticular diseases.

Adult↗
PubMed1998

HLA-DR gene frequencies in a Zaïrean population with particular reference to rheumatic diseases.

Epidemiological studies have shown that rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus are uncommon in black Africans, and in this population the prevalence and the clinical features of these rheumatic diseases are variable. Environmental and genetic factors have been pointed out to explain this variability. In the present study, HLA-DR genes have been determined in a Zaïrean population in order to compare our results with those found elsewhere in other black populations of the same Bantu origin. Our results show that the frequency of HLA-DR1 is higher than in Nigerians, Zimbabweans and Xhosas, the decrease in Xhosas being statistically significant (p < 0.006). The HLA-DR3 frequency is higher in Zaïreans than in Nigerians but not significantly, while it is lower than in Xhosas (p < 0.003) and in Zimbabweans (not significant). The HLA-DR4 frequency is higher in Zaïreans than in Nigerians but it is lower than in Xhosas and Zimbabweans; the differences are not statistically significant. The HLA-DR8 frequency is lower in Zaïreans than in Nigerians while it is higher than in Xhosas (p < 0.002) and in Zimbabweans (not significant). These data suggest that genetic factors partly explain the clinical and epidemiological variability of rheumatic diseases in black Africans.

Adult↗
PubMed1998

Placental pathology in systemic lupus erythematosus: a prospective study.

OBJECTIVES: Systemic lupus erythematosus and antiphospholipid antibody, often identified in patients with systemic lupus erythematosus, are associated with poor pregnancy outcome. This study distinguishes between the effect of each of these factors on gestational outcome and placental pathologic conditions in pregnant patients with systemic lupus erythematosus. STUDY DESIGN: Thirty-seven pregnancies and 40 placentas from 33 women with systemic lupus erythematosus were studied prospectively. RESULTS: Systemic lupus erythematosus alone, but not systemic lupus erythematosus activity, was associated with increased spontaneous abortions, preterm gestations, and fetal growth restriction. Placental correlates were ischemic-hypoxic change, decidual vasculopathy, decidual and fetal thrombi, chronic villitis, and decreased placental weight. Extensive infarction and fetal death were important antiphospholipid antibody-related findings. CONCLUSIONS: Decidual vasculopathy/coagulopathy appears to mediate the antiphospholipid antibody-related and much of the systemic lupus erythematosus-related deleterious effect on the placenta and gestational outcome. The presence of antiphospholipid antibody largely, but not invariably, predicts fetal death. Antiphospholipid antibody-independent chronic villitis may represent a second mechanism of systemic lupus erythematosus-related change.

Adult↗
PubMed1998

The fetal and neonatal consequences of maternal alloimmune thrombocytopenia.

Alloimmune thrombocytopenia is a relatively common and under-recognized entity. Prospective screening studies have suggested that at least 1 in every 1000 babies will be affected. While the severity of prospectively identified neonates is not as great as those 'routinely' identified as newborns, the incidence of intracranial haemorrhage in the fetus and neonate is the highest for any immune thrombocytopenia. Diagnosis is complex for the laboratory in view of the large number of platelet antigens and the importance of having sufficient numbers of typed controls. The importance of identifying the affected newborn extends to the likely need for antenatal management of the subsequent affected fetus. Studies to determine the optimal approach to this problem are ongoing. Ideally, prenatal screening of all pregnant women could be performed but this is not currently in practice.

Blood Platelets↗
PubMed1998

Feto-maternal alloimmune thrombocytopenia: antenatal therapy with IvIgG and steroids--more questions than answers. European Working Group on FMAIT.

The optimal antenatal therapy for fetal thrombocytopenia has not been determined. We analysed 37 cases managed by maternal therapy and observed a successful outcome of maternal treatment in 26% of IvIgG cases and in 10% of steroid-treated cases. The significance of a plateau of the fetal platelet counts during pregnancy, 41% of IvIgG cases and 20%, of cases treated with steroids, is uncertain. It may indicate a stabilization of thrombocytopenia, hence a beneficial effect of therapy, or the natural course of the platelet count in a low-risk pregnancy. Overall outcome was unpredictable, but amongst the therapy failures there were proportionally more severely affected siblings. Further multicentre studies are necessary to establish the optimal antenatal management of high-risk pregnancies.

Adrenal Cortex Hormones↗