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Biomedical subjects

W M Smid

Publications and source records attributed to W M Smid.

At least 19 recordsLinked to original sources
PubMed2005

Prolonged platelet preservation by transient metabolic suppression.

BACKGROUND: In this study whether metabolic suppression can be used to preserve platelet (PLT) function during prolonged storage was investigated. STUDY DESIGN AND METHODS: Washed human PLTs were incubated without glucose and with antimycin A to block energy generation. Metabolic suppressed PLTs (MSPs) were stored for 72 hours at different temperatures to find the optimal storage temperature. Controls were incubated with 5 mmol per L glucose and stored at 22 and 4 degrees C. RESULTS: Following metabolic recovery with glucose, MSPs stored at 37, 22, and 4 degrees C showed an increase in basal P-selectin expression (PSE) reaching greater than 40 percent after about 2, 20, and 48 hours; a decrease in thrombin receptor-activating peptide SFLLRN (TRAP)-induced PSE inversely related to the increase in basal PSE; and a decrease in TRAP-induced aggregation reaching less than 30 percent after about 4, 24, and more than 72 hours. When compared with control suspensions, MSPs stored at 4 degrees C better preserved a low basal PSE and in addition showed a better adhesion to surface coated-von Willebrand factor and fibrinogen in a flow chamber. CONCLUSION: Metabolic suppression before storage at 4 degrees C contributes to better preservation of PLT function.

Blood Platelets↗
PubMed2000

Lymphocyte subset abnormalities in multitransfused HIV-negative haemophilia A patients are not due to chronic hepatitis C virus infection.

Several abnormalities of immune parameters have been described in HIV-negative haemophiliacs, including changes in numbers of T4 and T8 cells, T4/T8 ratio and numbers of activated T cells. To assess the contribution of hepatitis C to these abnormalities, we compared lymphocyte subsets in 20 HIV-negative HCV-positive haemophilia A patients and in 14 non-haemophiliacs with chronic hepatitis C with those in 18 healthy controls. In haemophilia patients, higher numbers of T lymphocytes and activated T8 cells, lower numbers of B lymphocytes and a normal T4/T8 ratio were seen. These differences were either not demonstrated in hepatitis C controls or were less pronounced and in the opposite direction. We conclude that haemophilia A patients showed abnormalities in lymphocyte subsets that could not be attributed to chronic hepatitis C.

Adult↗
PubMed1999

Natural history of hepatitis C in HIV-negative patients with congenital coagulation disorders.

BACKGROUND/AIMS: Knowledge of the natural history of hepatitis C is useful for counselling patients and planning treatment. More data are needed from unselected patient groups without concomitant disease. The aim of this study was to describe the natural history of hepatitis C, two decades after infection, in a homogeneous and well-defined group of HIV-negative patients with congenital coagulation defects who had not received specific therapy for chronic hepatitis C. METHODS: Medical history, physical examination, laboratory tests and abdominal ultrasonography were performed in 45 HCV-RNA positive, HIV-negative patients, mainly haemophiliacs, from a single centre. Patients were classified according to results of ultrasonography. RESULTS: Two patients had experienced an episode of variceal bleeding; all others were asymptomatic. None had ascites. HCV-RNA titres were >500000 copies/ml in 23 patients, genotype was 1 in 31 patients. Forty (89%) had elevated transaminases, liver synthesis function was diminished in 7 (16%), and platelet count in 8 (18%). Ultrasonography was normal in 26 (58%) patients, 12 (27%) had isolated splenomegaly, and 7 (16%) had liver nodularity compatible with cirrhosis. Univariate analysis disclosed higher transaminases and gammaGT, higher age at acquisition of infection and higher present age as risk factors for more advanced disease. Of these, only higher present age was an independent predictor in multivariate analysis. CONCLUSIONS: Median 19 years after infection, 58% of patients had no other signs of liver disease than raised transaminases, 16% had cirrhosis on ultrasonography. Only 2/45 patients had symptomatic disease. Higher present age is the main risk factor for advanced disease in this group.

Adolescent↗
PubMed1998

Total knee and hip arthroplasty in haemophilic patients.

UNLABELLED: We evaluated the long-term results of three total hip and nine total knee arthroplasties in nine haemophilic patients with disabling pain and end-stage arthropathy. These patients have been followed over a period of 2-12 years (mean 6.9). One patient had a post-operative haematoma, which was evacuated; two patients required manipulation of the knee because of a limited range of motion. There were no infections. At follow-up, all but two patients were completely free of pain; two patients had occasional pain. The functional improvement was impressive with an average increase in the knee score from 37 to 80 points post-operatively. The hip score increased from 36 to 85 points. The range of motion was increased in seven joints, unchanged in two joints and decreased in three. One total hip arthroplasty was revised after 9 years for aseptic loosening. One total knee demonstrated nonprogressive radiographic evidence of aseptic loosening. Median consumption of coagulation factor concentrate in severe haemophiliacs decreased from 47.00 U yr-1 (range 16.000-144.000) before surgery, to 25.000 U yr-1 (range 18.000-132.000) at 2 years after surgery. CONCLUSION: Hip and knee arthroplasty is a valuable option in symptomatic haemophilic patients with disabling arthropathy, in order to obtain pain relief and functional improvement. It is associated with a low rate of complications and may reduce the need for substitution of factor VIII and IX.

Adult↗
PubMed1998

Hyperfibrinogenolysis in disseminated adenocarcinoma.

We present the case of a 42-year-old woman with a recently acquired bleeding tendency. Coagulation studies and response to antifibrinolytic therapy suggested primary hyperfibrinogenolysis: markedly low levels of fibrinogen and alpha2-antiplasmin, normal levels of antithrombin III, protein C and protein S combined with an only borderline low number of platelets without evidence of microangiopathic haemolytic anaemia. A suspected causative adenocarcinoma of the lung was demonstrated. She was treated successfully with tranexamic acid and cryoprecipitate, until the tumor progressed and hyperfibrinogenolysis progressed to diffuse intravascular coagulation. Differential diagnosis of these coagulation disorders, with similar etiology, clinical and laboratory findings is reviewed. Therapeutic implications are discussed.

Adenocarcinoma↗
PubMed1998

Differences in immune response between HCV positive, HIV negative haemophilia A and B patients.

We measured numbers of lymphocytes and subsets in seven HIV negative, HCV positive severe haemophilia B patients, before and after substitution was changed from prothrombin complex concentrate to monoclonally purified concentrate. Data were compared with controls and our previous findings in haemophilia A. At baseline, haemophilia B patients did not differ from controls. After two years, T helper cells showed an increase (p = 0.028), while a rise in B cells approached statistical significance (p = 0.063). Haemophilia A patients showed increased numbers of activated non-B lymphocytes (p = 0.003) and lowered numbers of B cells (p = 0.001) at baseline. After two years activated non-B lymphocytes decreased (p = 0.004), as did the CD4/CD8 ratio (p = 0.002), due to increasing numbers of CD8 positive cells (p = 0.087). Our data suggest minor inhibition of the immune system in haemophilia B patients, which recovers after changing therapy to a monoclonally purified product. These findings contrast with the excessive immune stimulation in haemophilia A. The observed differences might be due to the administered concentrates.

Adolescent↗
PubMed1998

Platelets stored in a new-generation container differences between plasma and platelet additive solution II.

BACKGROUND AND OBJECTIVES: In order to preserve platelet concentrates (PCs) with high yields, a new polyolefin platelet storage container (PL 2410, 1.3L, Baxter, La Châtre, France) with increased gas permeability in combination with a larger surface area has been developed. The storage capacity was studied with platelets in plasma and platelets additive solution. MATERIALS AND METHODS: Platelet concentrate pools (PCs) of different yields suspended in either plasma (PCs-PL; n = 30) or PAS II (PCs-PAS; n = 37) were prepared. For preparation of PCs with a low, intermediate and high number of platelets 3, 5 and 6 buffy coat (BCs) were pooled with different volumes of plasma and 5 and 6 BCs were pooled with different volumes of PAS II, in order to obtain PCs of equal volumes comparable with routine conditions. All PCs were stored on a flatbed shaker at 22+/-2 degrees C and evaluated on days 1, 2, 5 and 7 by determining platelet and white cell counts, pH (37 degrees C), pO2, pCO2 and swirling score. RESULTS: Platelet yields ranged from 1.5 up to 5.5 x 10(11) platelets/U. On day 7 all PCs-PL (n = 4) with platelet yields above 4.5 x 10(11)/U had a pH value below 6.8 (range 5.91-6.79). While 7 of 8 PCs-PAS units with platelet yields above 4. 0 x 10(11)/U showed a pH value below 6.8 (range 6.31-6.70). CONCLUSION: During 7 days of storage in a new 1.3-liter platelet container, the pH was maintained above 6.8 in PCs in plasma with a yield between 1.5- and 4.5 x 10(11)/U; when PAS II was used, the maximum platelet yield allowed for comparable pH maintenance was somewhat lower (4.0 x 10(11)/U).

Adult↗
PubMed1997

Soluble interleukin 2 receptor and soluble CD8 levels in previously treated human immunodeficiency virus-negative hemophiliacs multiply transfused with a monoclonal antibody-purified factor VIII concentrate.

BACKGROUND: Serum levels of the soluble interleukin 2 receptor (sIL-2R) and soluble CD8 (sCD8) may be used as markers of T-cell activation. The course of serum levels of sIL-2R and sCD8 in hemophiliacs who were treated first with an intermediate-purity factor VIII concentrate and then with a monoclonal antibody (MoAb)-purified factor VIII concentrate are reported. STUDY DESIGN AND METHODS: Serum samples taken before the administration of the MoAb-purified concentrate and after 2 and 5 years of its administration to 20 human immunodeficiency virus-negative patients with hemophilia A were analyzed. Eighteen healthy age-matched men were used as controls. RESULTS: The sIL-2R and sCD8 levels were higher in patients treated with intermediate-purity concentrates than in controls (p = 0.006 and p = 0.0005, respectively). The sIL-2R levels showed a decrease after 5 years of treatment with the MoAb-purified concentrate (p = 0.018 for the difference between 2 and 5 years), to levels that were not significantly different from those in controls. Although sCD8 levels tended to decrease at 5 years (p = 0.09, for the difference between 2 and 5 years), they remained higher than those in controls (p = 0.0005 and p = 0.0016 at 2 and 5 years, respectively). The ratio of sCD8 and sIL-2R tended to increase between 2 and 5 years (p = 0.07). The sIL-2R and sCD8 levels were not related to the numbers of T-lymphocytes and HLA-DR-positive T-lymphocytes in peripheral blood. Nor was a relation demonstrated between sIL-2R levels and CD4-positive cell numbers or between sCD8 levels and CD8-positive cell numbers. Although a relation with chronic hepatitis C cannot be excluded, it seems more likely that changes in sIL-2R levels are due to the use of the MoAb-purified concentrate. CONCLUSION: Elevated levels of sIL-2R and sCD8 were found in multiply transfused human immunodeficiency virus-negative hemophiliacs. After treatment was changed to the use of a MoAb-purified concentrate. sIL-2R levels decreased. These findings suggest a change in immune stimulation that is remarkable, because signs of activation in the effector phase seem to have continued despite normalization in the proliferative phase.

Adult↗
PubMed1996

Randomized placebo-controlled trial of granulocyte-macrophage colony-stimulating factor in patients with chemotherapy-related febrile neutropenia.

PURPOSE: To determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF) used in addition to standard inpatient antibiotic therapy shortens the period of hospitalization due to chemotherapy-induced neutropenic fever. PATIENTS AND METHODS: One hundred thirty-four patients with a hematologic (n = 47) or solid tumor (n = 87) who had severe neutropenia (< 0.5 x 10(9)/L) and fever (> 38.5 degrees C once or > 38 degrees C twice over a 12-hour observation period) were randomly assigned to receive GM-CSF 5 micrograms/kg/d (n = 65) or placebo (n = 69) in conjunction with broad-spectrum antibiotics for a minimum of 4 days and a maximum of 14 days. GM-CSF/placebo and antibiotics were stopped if the neutrophil count was greater than 1.0 x 10(9)/L and temperature less than 37.5 degrees C during 2 consecutive days, or for a leukocyte count > or = 10 x 10(9)/L, both followed by a 24-hour observation period (hospitalization period). RESULTS: Compared with placebo, GM-CSF enhanced neutrophil recovery. Median neutrophil counts at day 4 were 2.5 x 10(9)/L (range, 0 to 25) in the GM-CSF arm and 1.3 x 10(9)/L (range, 0 to 9) in the placebo arm (P < .001). No significant difference was observed with regard to median number of days with less than 1.0 x 10(9)/L neutrophils (4 v 4) or days of fever (3 v 3). The median number of days patients were hospitalized while on study was comparable in the GM-CSF and placebo groups at 6 (range, 3 to 14) versus 7 (range, 4 to 14), respectively, according to an intention-to-treat analysis (P = .27). Quality-of-life scores in 90 patients demonstrated significant differences in favor of the placebo group. Hospital costs were significantly higher for GM-CSF-treated patients if GM-CSF was included in the price (median costs, $4,140 [US] for GM-CSF v $590 for placebo; P < .05). CONCLUSION: These results indicate that GM-CSF does not affect the number of days for resolution of fever or the hospitalization period for this patient group, although a significant effect of GM-CSF was observed on neutrophil recovery.

Adolescent↗
PubMed1996

Effects of chronic factor VIII substitution on immune parameters in HIV seronegative haemophiliacs: a comparison between cryoprecipitate and factor VIII concentrate.

Chronic substitution therapy of HIV-negative haemophiliacs with factor VIII products can result in abnormalities of ex-vivo measured immune parameters. To assess a possible relation between these abnormalities and product purity, we analyzed two groups of HIV-negative HCV-positive haemophiliacs, one treated with cryoprecipitate exclusively, the other with more purified factor VIII concentrates. Compared to age matched non-transfused male controls, increased numbers of white cells, granulocytes, IgG and IgM levels and decreased CD4+/CD8+ ratios were found in both patient groups. In the concentrate receivers, the numbers of mononuclear cells, CD4+, CD8+ and CD3+/HLA-DR+ cells indicating activated T-cells, were higher than in the cryoprecipitate group. In conclusion, both cryoprecipitate and intermediate/high purity concentrate recipients showed immune parameter abnormalities. These abnormalities tended to be somewhat more pronounced in patients treated with concentrates. By now there is no indication of the clinical relevance of the abnormalities in previously treated HIV seronegative haemophiliacs.

Adolescent↗
PubMed1996

Augmented procoagulant activity in cancer patients, treated with recombinant interferon-gamma in addition to recombinant tumor necrosis factor-alpha and melphalan.

Several investigators have reported that interferon-gamma (IFN gamma) can alter tumor necrosis factor alpha induced effects in vitro. We assessed in vivo effects of recombinant interferon-gamma (rIFN gamma) on recombinant tumor necrosis factor-alpha (rTNF alpha) induced activation of systemic blood coagulation in a non-randomized study in 20 consecutive cancer patients. Eight patients were treated with rIFN gamma prior to and during hyperthermic isolated limb perfusion with rTNF alpha and melphalan (IFN gamma group). They were compared with twelve patients who did not additionally receive rIFN gamma (non-IFN gamma group). Before start of perfusion, higher levels of TNF alpha, F1+2 and TAT levels were found in the IFN gamma group. Fibrinogen and ATIII levels tended to be lower in this group. High TNF alpha levels, due to leakage during perfusion, were associated with activation of coagulation in all patients, that became obvious after the end of perfusion, when heparin treatment had been antagonized. Activation, measured by increased F1+2 and TAT levels, was significantly stronger in the IFN gamma group. Monocytic TF remained low, possibly due to shedding of TF positive vesicles and/or sequestration of TF positive activated monocytes against the vessel wall. In both groups F1+2 and TAT levels declined 24 h after the perfusion, whereas monocytic TF increased to levels that were higher in the IFN gamma group. In conclusion, our data confirm a strong activation of coagulation induced by rTNF alpha in cancer patients. They suggest that rIFN gamma may lead to a slight activation of coagulation and augments TNF alpha induced procoagulant activity. These effects may be due to rIFN gamma induced sustained monocytic TF activity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Subcutaneous low-molecular weight heparin or oral anticoagulants for the prevention of deep-vein thrombosis in elective hip and knee replacement? Fraxiparine Oral Anticoagulant Study Group.

OBJECTIVE: To compare efficacy, safety, and feasibility of adjusted-dose oral anticoagulants (OAC) versus fixed-dose subcutaneous low molecular weight heparin (LMWH) for the prevention of deep venous thrombosis (DVT) in patients who have undergone elective hip or knee replacement. DESIGN: Multicentre, single blind randomised trial. OAC (acenocoumarol, target International Normalised Ratio, 2.0-3.0) and LMWH (nadroparine, 60 aXa IU/kg once daily) were started preoperatively and continued for 10 days. All outcome measures were adjudicated by an independent committee unaware of treatment allocation. SUBJECTS: 672 consecutive patients scheduled for elective hip or knee replacement surgery. All patients wore bilateral graduated compression stockings. MAIN OUTCOME MEASURES: The endpoint for the assessment of efficacy was venography confirmed DVT or confirmed symptomatic pulmonary embolism. The endpoint for the assessment of safety was clinically important bleeding during study treatment or within 48 h of the end of treatment. RESULTS: Among the 517 patients with interpretable venograms, 391 had a hip replacement and 126 had a knee implant. DVT was demonstrated in 50 (20%) of 257 patients allocated to OAC and 43 (17%) of 260 patients allocated to nadroparine (p = 0.45), for an absolute difference in DVT incidence of 2.9% in favour of nadroparine (95% CI, -3.7-9.5). Clinically important bleeding occurred in eight (2.3%) of the 342 oral anticoagulant treated patients and in five (1.5%) of the 330 nadroparine treated patients (p = 0.62), for an absolute difference in favour of nadroparine of 0.8% (95% Cl, -1.3-2.9). CONCLUSION: Patients who undergo major orthopaedic operations have a high risk of venous thromboembolism. Once daily fixed-dose subcutaneous nadroparine is at least as efficacious and safe as daily adjusted OAC for prophylaxis against DVT after hip or knee implantation but is more simple to administer.

Administration, Oral↗
PubMed1994

Severe bleeding caused by an inhibitor to coagulation factor V: a case report.

A 67-year-old man with a severe bleeding due to a high level of factor V inhibitor (maximum level of 350 Bethesda units) is described. Coagulation abnormalities improved initially during treatment with prednisolone in combination with cyclophosphamide. Subsequent treatment with either cyclophosphamide or cyclosporin alone was ineffective. After more than 2 years the inhibitor became undetectable after a prolonged period of high dose steroid therapy, but the patient remained steroid dependent. Therapeutic strategies for patients having a factor V inhibitor are discussed.

Aged↗