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Biomedical subjects

P M Yuen

Publications and source records attributed to P M Yuen.

At least 109 records · Page 6Linked to original sources

Effect of subcutaneous administration of recombinant human erythropoietin on plasma protein C, protein S, and antithrombin III levels in patients on continuous ambulatory peritoneal dialysis.

The effect of subcutaneous administration of recombinant human erythropoietin (rHuEPO) on plasma natural coagulation inhibitors (protein C, protein S, and antithrombin III) was evaluated in 10 uremic patients on continuous ambulatory peritoneal dialysis (CAPD). These patients were commenced on a 16 week-course of twice weekly rHuEPO by the subcutaneous route. The hemoglobin increased significantly from 6.9 +/- 1.3 g/dl to 9.6 +/- 1.9 g/dl after subcutaneous rHuEPO treatment (p less than 0.01) at an average dose of 84 +/- 9 U/kg body wt/week. With rHuEPO therapy, a significant increase in platelet counts was observed, albeit within the normal range. A significant increase in the prothrombin time was demonstrated at 6 weeks after treatment and increased activated partial thromboplastin time was observed at 6 weeks and 16 weeks after rHuEPO administration although these measurements still remained in normal range. CAPD patients have comparable or even higher plasma levels of natural coagulation inhibitors compared with healthy controls supporting our previous findings that patients on CAPD have normal plasma levels due to an effective compensatory production despite peritoneal losses of these proteins with CAPD. No change in either the immunological or the functional activity of these natural coagulation inhibitors was demonstrated with rHuEPO therapy and clinical thrombosis was not observed during and after rHuEPO therapy. We conclude that there is no laboratory evidence of increased risk of thrombogenesis due to reduction of natural coagulation inhibitors with rHuEPO therapy.

Administration, Cutaneous↗

Effect of hemodialysis on protein C, protein S, and antithrombin III levels.

We studied the effect of hemodialysis on natural coagulation inhibitors including protein C (PC), protein S (PS), and antithrombin III (AT III), as well as the correlations between the antigen level (immunological activity) and functional activity of individual coagulation inhibitor. Plasma AT III, PS, and PC were measured in 20 uremic patients on maintenance hemodialysis immediately before, during, and after dialysis treatment. These values were compared with those obtained from 20 matched healthy controls. Plasma PC and total PS antigen levels were measured by enzyme immunoassay. The plasma AT III antigen level was determined by Laurell rocket immunoelectrophoresis. Functional activities of PC and AT III were determined by the amidolytic method. Free PS antigen level was quantitated by measuring the free PS-related antigen after the sample was treated with polyethylene glycol to remove the C4b-binding protein. Uremic patients on maintenance hemodialysis had a higher total PS antigen level, but a lower free PS antigen level compared with the controls. Both the antigen level and functional activity of AT III in uremic patients were significantly lower than those of controls. Their predialysis plasma PC antigen level and functional activity were not different from those of normal controls. A significant correlation between the antigen level and functional activity of PC, PS, and AT III was demonstrated in healthy controls, but not in hemodialysis patients. No significant change in the level of AT III or PS was observed with hemodialysis, but a progressive increase of functional activity of PC was documented with hemodialysis. Furthermore, the coefficient of correlation between the antigen level and functional activity of PC improved significantly with dialysis treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Locally metastasizing vascular tumor. Spindle cell, epithelioid, or unclassified hemangioendothelioma?

The authors report the case of a 2-year-old boy with a recurrent and locally metastasizing, spindle cell, vascular tumor with histiocytoid cells involving the skin, subcutaneous tissue, and muscle of the right forearm, the right distal radius and ulna, and multiple lymph nodes of the right axilla. Diagnoses of hemangioma, hemangiopericytoma, angiomatosis, spindle cell hemangioendothelioma, and malignant hemangioendothelioma were made on successive excision specimens. The soft tissue of the right arm became diffusely enlarged, and a severe syndrome developed that was similar to that described by Kasabach and Merritt. The limb was amputated above the elbow, the axillary lymph nodes were cleared, and a total dose of 6,000 centigrays axillary radiation was given. After operation, the Kasabach-Merritt syndrome resolved. Despite the lymph node metastases and multiple tissues involved, the patient has remained well 6 years after surgery. Although the tumor exhibited some of the histologic features of a spindle cell hemangioendothelioma, the low-grade aggressive behavior resembled that of an epithelioid hemangioendothelioma. The reported case cannot be classified into any of the recognized categories or subdivisions of vascular tumors.

Bone Neoplasms↗

Gastric emptying in the postpartum period.

We measured gastric emptying, using the technique of paracetamol absorption, in eight women on their first and third postpartum day. Gastric emptying was rapid and there was no difference between the first and third day in the time to peak plasma concentration of paracetamol. Six women returned after six weeks for a further study. Gastric emptying was still rapid but the metabolism of paracetamol appeared to be slower than that found during the immediate postpartum period. These findings suggest that fluid fasting guidelines in patients more than one day postpartum need not be different from those in non-pregnant patients.

Absorption↗

Acute urinary retention caused by a unilateral hematometra.

We describe a unilateral hematometra with an associated hematosalpinx causing acute retention of urine in a female adolescent. Normal menstruation had occurred from the uterine cavity on the unaffected side. Treatment was by abdominal metroplasty with complete excision of the uterine septum and a terminal cuff salpingostomy. Urological investigation revealed ipsilateral renal agenesis.

Abdominal Pain↗

Protein C, protein S, and antithrombin III levels in patients on continuous ambulatory peritoneal dialysis and hemodialysis.

Patients undergoing dialysis are subject to risk of thrombotic complications. We studied the plasma levels of natural coagulation inhibitors including protein C (PC), protein S (PS), and antithrombin III (AT III) in 20 patients on hemodialysis and 20 patients on continuous ambulatory peritoneal dialysis (CAPD). Total PS antigen, free PS antigen, immunological and functional activities of PC and AT III were measured. Hemodialysis patients had a higher total PS level but a lower free PS level compared with healthy controls. Both the immunological and functional activities of AT III in hemodialysis patients were significantly lower than those of controls. With the exception of total PS level, CAPD patients had comparable or even higher plasma level of natural coagulation inhibitors compared with healthy controls. Furthermore, the plasma levels of PC, PS, and AT III were significantly lower in hemodialysis patients compared with CAPD patients despite greater daily losses of PC, PS, and AT III through urinary and peritoneal routes in patients on CAPD treatment. Most of the AT III in the peritoneal dialysate was still functionally active but most of the PC was inactive. Our observations suggest an effective turnover and production of these natural coagulation inhibitors in patients on CAPD therapy but a similar compensatory mechanism does not operate efficiently in patients receiving hemodialysis.

Adult↗

Relationship between maternal antithrombin III and protein C/protein S levels before, during and after delivery.

The relationship between plasma levels of protein C, protein S and antithrombin III was examined in a group of normal pregnant Chinese women with singleton pregnancies to study the changes in the anticoagulant system in relation to pregnancy, labour and the puerperium. A significant correlation was found between protein C and antithrombin III both before labour and postpartum, and the ratio was close to unity. When the two groups are combined, a highly significant correlation was found (r = 0.758; p less than 0.001). The correlation is not observed at delivery when the ratio becomes very variable and in general greater than unity. The correlation between protein S and antithrombin III was 0.592 before labour and -0.532 at delivery, but both failed to reach statistical significance because of the small numbers. When postpartum concentration of protein C, protein S and antithrombin III is related to interval between sampling and delivery, significant correlation was found only with protein S. The results of this study suggest that the plasma level of protein C and probably protein S is correlated with that of antithrombin III during pregnancy, labour and the puerperium.

Antithrombin III↗

Coagulation and anticoagulation systems in newborns--correlation with their mothers at delivery. Lower levels of anticoagulants and fibrinolytic activity in the newborn.

The neonatal period is probably the only time when a higher incidence of spontaneous thromboembolic complications may occur in the otherwise normal healthy individual, and this may be related to the activation of the coagulation system at the time of parturition. This study was performed to look at the newborn coagulation and anticoagulation systems and compare these with the changes in the maternal circulation in normal cases. Paired umbilical cord venous and maternal venous blood samples were obtained and plasma levels of protein C, protein S, antithrombin III, fibrinopeptide A, fibrinogen, plasminogen, and fibrinolytic inhibitory activity were measured. The maternal plasma level was significantly higher in all cases except for fibrinopeptide A which was similar, and for fibrinolytic inhibitory activity which was lower (p less than 0.05). A significant correlation exists between maternal and newborn protein C levels (p less than 0.02) and fibrinolytic inhibitory activity (p less than 0.05). The findings indicate that parturition leads to a similar degree of activation of the newborn coagulation system as shown by the fibrinopeptide A level. As their anticoagulants and fibrinolytic activity levels are lower and the fibrinolytic inhibitory activity is higher, the newborns are thus predisposed to thrombosis even in the absence of complications such as sepsis.

Antithrombin III↗

Fibrinopeptide A levels in maternal and newborn plasma.

Plasma fibrinopeptide A (FPA), a dynamic measure of intravascular coagulation, was determined in 70 healthy Chinese women during normal pregnancy, labour, delivery and the early puerperium and compared to a group of healthy non-pregnant adult controls. In the normal controls the plasma FPA level (mean +/- SD) was 1.43 +/- 0.46 ng/ml. During pregnancy and labour, the FPA levels were 3.05 +/- 0.98 ng/ml and 11.47 +/- 4.43 ng/ml, respectively, and it reached a peak of 32.95 +/- 11.66 ng/ml at parturition, then falling to 6.15 +/- 2.52 ng/ml in the early puerperium. All these levels were significantly higher (p less than 0.001) compared to controls. Fifteen of the 21 mothers with blood sampling during parturition also had umbilical cord blood taken for determination of FPA level. There was no significant difference between the maternal (34.07 +/- 10.12 ng/ml) and cord (31.06 +/- 12.67 ng/ml) plasma FPA levels. It is concluded that the hypercoagulable state in women during pregnancy and the puerperium is associated with increased intravascular coagulation activity, and that increased intravascular coagulation activity also occurs in the fetus during parturition. This observation may account for the increased risk of thrombotic disorders observed in pregnant and parturient women as well as in the newborn.

Female↗

Protein S and protein C levels in Chinese women during pregnancy, delivery and the puerperium.

The plasma levels of protein S and protein C related antigens were determined in a group of normal pregnant Chinese women and a group of normal non-pregnant controls, using the sandwich technique of enzyme immunoassay with commercial kits. Compared with non-pregnant controls, plasma protein S levels were significantly lower during pregnancy, labour, parturition and the early puerperium. There was no significant difference in protein S levels between pregnancy, labour and puerperium. On the other hand, maternal plasma protein C levels during pregnancy and before delivery were similar to those in controls, but a significant increase was found during the third stage of labour. This increase did not persist into the early puerperium. The observed increase in protein C level immediately after delivery in our study may represent a physiological response to counter the tendency towards venous thrombosis in the parturient women, and may help to explain the almost negligible occurrence of thromboembolism in Chinese obstetric patients.

China↗

Pulmonary function in thalassemia major.

Pulmonary function tests were evaluated in 28 Chinese patients with beta-thalassemia major receiving regular transfusions and desferoxamine, and in 34 height-matched normal Chinese children. Comparison of lung function using analysis of covariance with reference to standing height showed that patients with thalassemia had a proportional decrease in forced vital capacity and forced expiratory flow volume in 1 second, whereas their expiratory flow rates, residual volume, and total lung capacity were comparable to those in normal children. The single-breath carbon monoxide diffusion capacity was normal. Our findings suggest that children with thalassemia major have mild restrictive lung disease. The previous controversy regarding the presence of restrictive or obstructive lung disease in patients with thalassemia may be related to the use of inappropriate control values.

Adolescent↗

Haemophilic pseudotumours of the mandible: report of a case in a one-year-old child.

Pseudotumours of bone are an uncommon complication of severe haemophilia and only seven cases occurring in the mandible have been reported previously in the English literature. If treated early the condition appears to have a better prognosis and so it should be included in the differential diagnosis of any slowly progressive swelling of hard and soft tissues occurring in a patient with severe haemophilia. However aspiration and biopsy should be avoided if possible. Previous authors have advocated a variety of invasive procedures for this condition. A further case is described which is unique in the age at which the bilateral lesions developed, in the successful outcome of conservative management and in the dental observations.

Diagnosis, Differential↗

Processing of major ABO-incompatible bone marrow for transplantation by using dextran sedimentation.

BACKGROUND: Various open and semi-closed methods are used for red cell (RBC) depletion and hematopoietic progenitor cell (HPC) enrichment of bone marrow (BM) in vitro, but with variable efficacy. A simple, efficient, and safe method using dextran 110k was developed. STUDY DESIGN AND METHODS: An equal volume of 4.5-percent dextran was applied to major ABO-incompatible BM in transfer bags and sedimentation was allowed for 30 minutes. RBCs, nucleated cells (NCs), and mononuclear cells (MNCs) from BM allografts before and after dextran sedimentation (DS) were counted. Flow cytometry, short-term cultures, and long-term cultures were performed to assay the respective recovery of CD34+ cells, colony-forming units (CFUs), and long-term culture-initiating cells (LTC-ICs). RESULTS: Sixteen BM collections were processed. The mean volume was 666 mL (range, 189-1355 mL). The mean +/-1 SD post-DS NC, MNC, CD34+ cell, and CFU counts per kg of the recipient's body weight were 4.11 +/-1.74 x 10(8), 8.98 +/- 3.68 x 10(7), 2.90 +/- 1.95 x 10(6), and 2.03 +/- 2.01 x 10(5), respectively, with the corresponding post-DS recovery being 90.6 percent, 90 percent, 92.4 percent, and 100.8 percent. The numbers of LTC-ICs in cultures (up to 12 weeks) of pre-DS and post-DS samples of five BM allografts were comparable (p = 0.91). Residual RBCs were 5.1 +/- 4.6 (0.1-14) mL with depletion of 96.5 +/- 3.2 percent. There was no significant difference in the mean absolute RBC count in post-DS BM allografts and in four ficoll-treated BM allografts (8.09 x 10(10) vs. 4.9 x 10(9); p = 0.206) and in eight major ABO-incompatible peripheral blood HPC collections (8.09 x 10(10) vs. 9.81 x 10(10); p = 0.87). No posttransplant hemolysis was encountered. Engraftment occurred at 22 +/- 7 days, which is similar to that of four transplants with ficoll-treated BM allografts (22 +/- 9; p = 0.611) and 54 unprocessed BM allografts (19 +/- 6; p = 0.129). CONCLUSION: DS is an efficient method of depleting RBCs in major ABO-incompatible BM allografts without significant loss of HPCs.

ABO Blood-Group System↗

A longitudinal study of cardiac function in children with cancer over 40 months.

A previous study demonstrated impaired systolic function in 29% of patients treated with anthracycline as part of their therapy for malignant disease. A follow-up echocardiographic study was performed to determine whether there had been further deterioration of cardiac function. At least 40 months after the first study, those patients in whom abnormal systolic function had been detected and who had not received further anthracycline were studied by echocardiography using the same protocol as the initial study (group A). A second group of pediatric oncology patients who had not been given anthracycline but who had previously had cardiac assessment was selected as a control group (group N). The age and sex distributions of the two groups were comparable. Group A comprised 29 patients assessed on 2 occasions at mean times of 46 months and 89 months from the last dose of anthracycline. The mean dose of anthracycline received was 233 mg/m2 (range 20-400). Nine of 16 patients and 4 of 5 patients who had abnormal ejection fraction (EF) and fractional shortening (FS) at first assessment had normal EF and FS at the second assessment. There were no significant changes in EF, FS, and left ventricular wall stress (LVWS) between the two examinations. In group N, 20 patients were assessed after a mean interval of 43 months. There were no significant changes in EF, FS, or LVWS between the two examinations. At the first but not the second examination there were significant differences in the left ventricular internal diameters, EF, FS, and LVWS between group A and group N. Mildly abnormal cardiac indices detected in children after cessation of treatment with anthracycline did not deteriorate in 3 to 4 years follow-up. A longer cardiac follow-up study is indicated to assess the late outcome.

Adolescent↗

Klebsiella pneumoniae meningitis in thalassemia major patients.

Two thalassemia major patients received regular blood transfusion and desferrioxamine chelation, and 1 patient had a splenectomy at 9 years of age. Both patients developed Klebsiella pneumoniae meningitis at age of 27 and 15 years. They died within a short time despite appropriate antibiotic treatment. Klebsiella meningitis may be more common in transfusion-dependent thalassemia patients.

Adolescent↗

Intracranial germ cell tumors in children with and without Down syndrome.

PURPOSE: Two Chinese children with Down syndrome affected by intracranial germ cell tumors are described. Because they represent two of eight affected patients in the current series from 1990 to 1996, it is postulated that such occurrence may be more than a coincidental event. PATIENTS AND METHODS: Two children with Down syndrome developed germ cell tumors in atypical intracranial sites that affected basal ganglion and cerebellum. The pathology showed germinoma and yolk sac tumor, respectively. These were treated by radical surgical resection and chemotherapy with cisplatin, etoposide, and bleomycin, but without radiotherapy. RESULTS: One patient survived 3 years without radiologic evidence of tumor. The other died from infective complications caused by severe myelosuppression after chemotherapy. CONCLUSIONS: Subtle neurologic manifestations in developmentally handicapped patients with intracranial space-occupying lesions could result in delayed diagnosis. Children with Down syndrome suffering from brain tumors may have a higher chance for germ cell tumors. Assay for alpha-fetoprotein and beta-human chorionic gonadotrophin could hasten diagnosis in some cases. This observation and review of literature suggest an increased risk of developing intracranial germ cell tumors in subjects with Down syndrome.

Antineoplastic Combined Chemotherapy Protocols↗

Up-regulation of cell growth associated with an extra Y chromosome in a child with beta-thalassemia major having undergone hematopoietic stem cell transplant.

An extra Y chromosome(s) is occasionally found in patients with various hematologic neoplasias; however, an association with hereditary blood diseases is unknown. In a child with beta-thalassemia who received a transplant with sex-mismatched umbilical cord blood and neonatal blood, fluorescent in situ hybridization (FISH) with probes to X and Y chromosomes revealed an extra Y signal in 19.3% of the hepatocytes and in 38.9% of the pretransplant peripheral blood cells, yielding YY/Y ratios of 0.24 and 0.64, respectively. In granulocyte colony-stimulating factor-mobilized autologous peripheral blood stem cells, the FISH ratio of interphase XYY cells to XY cells was 1.64, and there were 3.4 times more G-banded XYY metaphases than normal metaphases. Both FISH and polymerase chain reaction persistently demonstrated posttransplant mixed chimerism. There was a greater proportion of residual autologous XYY cells than XY cells with a mean posttransplant YY/Y ratio of 1.56 (n = 13) (1 SD = 0.33; range, 1.10 to 2.17). In vitro clonogenic assays yielded a normal number of colony-forming units but no growth in cultures without growth factor supplement. This study suggests that hematopoietic stem cells with an extra Y chromosome may upregulate cell growth in response to cytokine stimulation. A posttransplant preponderance of XYY cells might be attributable to an extra Y chromosome in hematopoietic stem cells withstanding the myeloablative conditioning regimen.

Cell Division↗

Effects of flt-3 ligand in combination with TPO on the expansion of megakaryocytic progenitors.

As an early acting growth factor, flt-3 ligand (FL) promotes the ex vivo expansion of hematopoietic stem and progenitor cells. The effect and mechanism of FL on the development of the megakaryocytic lineage remain unclear. In this study, we compared the effects of FL and stem cell factor (SCF) in combination with other megakaryocyte-promoting cytokines on the differentiation and proliferation of megakaryocytic progenitors and investigated the expression of flt-3 receptors on megakaryocytic cell lines. In liquid cultures of enriched CD34+ cells from human umbilical cord blood for 14 days, FL plus thrombopoietin (TPO), interleukin-3 (IL-3), and IL-6 promoted the expansion of nucleated cells, CD34+ cells, CD34+ CD38- cells, and megakaryocyte colony-forming units (CFU-MK) by 300 +/- 115-, 23.8 +/- 11.3-, 33.9 +/- 28.6-, and 584 +/- 220-fold, respectively. Replacing FL with SCF significantly decreased the yield of all cell types. Using murine bone marrow (BM) cells, we demonstrated that FL at a range of 0-100 ng/ml had no significant mitogenic effect on CFU-MK formation. TPO increased CFU-MK (p < 0.001) but the effect was not significantly modified by FL. While one human acute lymphoblastic leukemia sample expressed high levels of flt-3 receptor, the four megakaryocytic cell lines (Meg-01, CHRF-288-11, M-07e, and Dami) did not show any positive expression. Our data suggest that the present cytokine combination and expansion conditions provide an effective and potentially useful system for the clinical expansion of cord blood for bone marrow transplantation (BMT). FL alone did not stimulate megakaryocytopoiesis, possibly due to the lack of receptor expression on megakaryocytes. The effect of FL in augmenting the expansion of CFU-MK in liquid culture might be due to the early action of FL at the pluripotent stem cell stage.

Adjuvants, Immunologic↗