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Biomedical subjects

W B Gerrits

Publications and source records attributed to W B Gerrits.

At least 19 recordsLinked to original sources

Decreased coagulability has no clinically relevant effect on atherogenesis: observations in individuals with a hereditary bleeding tendency.

BACKGROUND: Hemostasis affects ischemic cardiovascular disease through its role in formation of occluding arterial thrombi. Several studies suggest that hemostasis also might play a role in atherogenesis. We investigated whether individuals with an inherited bleeding tendency are protected against development of atherosclerosis. METHODS AND RESULTS: A total of 76 individuals with an inherited bleeding tendency (hemophilia and von Willebrand disease) and 142 healthy controls were included in the present study. Early atherosclerotic vessel-wall changes were quantified by measurement of intima-media thickness in the carotid and femoral arteries by B-mode ultrasonography. To validate intima-media thickness measurements, measurements also were performed in 77 individuals with clinically proven atherosclerosis and in 34 healthy, age-matched controls. A large difference in intima-media thickness was found between individuals with proven atherosclerosis and healthy controls, in particular for the femoral artery (difference for carotid artery, 0.16 mm; femoral artery, 0.53 mm). Comparison between patients with a bleeding tendency and healthy controls showed only minimally reduced intima-media in femoral artery in individuals with a bleeding tendency (adjusted difference, -0.078 mm; 95% CI, -0.17 to 0.018 mm). Subgroup analysis revealed that in subjects with moderate to severe hemophilia, vessel walls were thinnest (adjusted difference, -0.10 mm; 95% CI, -0.27 to 0.061 mm). CONCLUSIONS: Hypocoagulability caused by hemophilia or von Willebrand disease has at most a limited effect on atherogenesis.

Adult↗

[Hyperhomocysteinemia as a risk factor for venous thrombosis].

In recent years research was done to elucidate the relation between an increased homocysteine concentration and arterial as well as venous thrombosis. Several case control studies showed that an elevated homocysteine concentration is an independent risk factor for primary and secondary venous thromboembolism. It is not clear whether lowering homocysteine levels by administration of folic acid, whether or not in combination with vitamin B12 and vitamin B6, decreases the risk of vascular events. Randomized secondary prevention trials are being conducted at this moment. It is recommended to await the results of these trials before screening for and treating of individuals with hyperhomocysteinaemia.

Adult↗

Vitamin supplementation reduces blood homocysteine levels: a controlled trial in patients with venous thrombosis and healthy volunteers.

Hyperhomocysteinemia is a risk factor for atherosclerosis and thrombosis and is inversely related to plasma folate and vitamin B12 levels. We assessed the effects of vitamin supplementation on plasma homocysteine levels in 89 patients with a history of recurrent venous thrombosis and 227 healthy volunteers. Patients and hyperhomocysteinemic (homocysteine level >16 micromol/L) volunteers were randomized to placebo or high-dose multivitamin supplements containing 5 mg folic acid, 0.4 mg hydroxycobalamin, and 50 mg pyridoxine. A subgroup of volunteers without hyperhomocysteinemia was also randomized into three additional regimens of 5 mg folic acid, 0.5 mg folic acid, or 0.4 mg hydroxycobalamin. Before and after the intervention period, blood samples were taken for measurements of homocysteine, folate, cobalamin, and pyridoxal-5'-phosphate levels. Supplementation with high-dose multivitamin preparations normalized plasma homocysteine levels (< or = 16 micromol/L) in 26 of 30 individuals compared with 7 of 30 in the placebo group. Also in normohomocysteinemic subjects, multivitamin supplementation strongly reduced homocysteine levels (median reduction, 30%; range, -22% to 55%). In this subgroup the effect of folic acid alone was similar to that of multivitamin: median reduction, 26%; range, -2% to 52% for 5 mg folic acid and 25%; range, -54% to 40% for 0.5 mg folic acid. Cobalamin supplementation had only a slight effect on homocysteine lowering (median reduction, 10%; range, -21% to 41%). Our study shows that combined vitamin supplementation reduces homocysteine levels effectively in patients with venous thrombosis and in healthy volunteers, either with or without hyperhomocysteinemia. Even supplementation with 0.5 mg of folic acid led to a substantial reduction of blood homocysteine levels.

Adult↗

Hyperhomocysteinemia and venous thrombosis: a meta-analysis.

Hyperhomocysteinemia is an established risk factor for atherosclerosis and vascular disease. Until the early nineties the relationship with venous thrombosis was controversial. At this moment ten case-control studies on venous thrombosis are published. We performed a metaanalysis of these reports. We performed a MEDLINE-search from 1984 through June 1997 on the keywords "homocysteine" or "hyperhomocysteinemia" and "venous thrombosis", which yielded ten eligible case-control studies. We found a pooled estimate of the odds ratio of 2.5 (95% CI 1.8-3.5) for a fasting plasma homocysteine concentration above the 95th percentile or mean plus two standard deviations calculated from the distribution of the respective control groups. For the post-methionine increase in homocysteine concentration we found a pooled estimate of 2.6 (95% CI 1.6-4.4). These data from case-control studies support hyperhomocysteinemia as a risk factor for venous thrombosis. Further research should focus on the pathophysiology of this relationship and on the clinical effects of reducing homocysteine levels by vitamin supplementation.

Adult↗

A population-based registry on paraproteinaemia in The Netherlands. Comprehensive Cancer Centre West, Leiden, The Netherlands.

Patients with monoclonal gammopathies comprise a heterogenous group. The few studies on incidence and follow-up are single-centre-based and may reflect referral bias. To avoid this, all patients (n=1275) in midwestern Netherlands with a newly discovered paraproteinaemia in 1991, 1992 and 1993 were included in a population-based registry and divided into four major diagnostic groups: multiple myeloma and plasmacytoma (n=230, 18%), other haematological diseases (n=141, 11%), paraprotein-related internal diseases (n=191, 15%) and monoclonal gammopathy of undetermined significance (MGUS, n=713, 56%). To avoid a possibly erroneous diagnosis, patients who were classified as having MGUS but who did not undergo confirmatory bone marrow examination were included in a separate group 'provisional MGUS' (n=524, 41%), whereas patients who did were classified as having 'definite MGUS' (n=189, 15%). The 'provisional MGUS' patients were relatively older and had more often a poor performance status, but differences between this and the 'definite MGUS' group were otherwise small. Patients complaining of general malaise more often had a full work-up of their paraproteinaemia. Bone pain, hypercalcaemia, high total protein, and high ESR occurred predominantly in the myeloma group, whereas fever or infection was less often seen in these patients. This registry of patients with paraproteinaemias provided valuable data related to all different diseases associated with paraproteinaemia.

Adult↗

[Radioactive phosphorus (32P); an old but not bad treatment for polycythemia vera].

OBJECTIVE: To determine if there is a place for radiophosphorus (32P) in the treatment of polycythaemia vera (PV) and essential thrombocytosis (ET). DESIGN: Retrospective. SETTING: Leyenburg Hospital, The Hague, the Netherlands. METHOD: Data on 144 patients with the diagnoses 'PV' or 'ET' from 1965 to 1994 were collected. Available data were insufficient in 19 of these. Regarding 125 patients, 80 with PV and 45 with ET, the survival and the frequency of acute leukaemia with various forms of treatment (32P, busulfan or combination of several treatment modalities) were studied. Moreover, in the PV group the duration of survival was compared with the expected duration of survival in a comparable group of the population. RESULTS: Of the 80 PV patients, five developed acute leukaemia: two in the 32P group (5%), two in the busulfan group (12%) and one in the group given combination therapy (4%). Of the 26 patients of the ET group treated with busulfan, one developed acute leukaemia (4%). The survival in the PV group was 4 years shorter than the expected duration of survival in a comparable group of the population. CONCLUSION: Since 32P is efficacious and causes little inconvenience, it should be the drug of first choice in the treatment of PV in the elderly.

Adult↗

Variability of the methionine loading test: no effect of a low protein diet.

The methionine loading test is used for the diagnosis of impaired methionine/homocysteine metabolism, in particular the transsulfuration pathway. Usually this test is performed on a low protein diet to control the intake of methionine. However, this is inconvenient and relatively expensive. In this study we compared the effects of a low protein diet and a standard diet on methionine loading test in 28 subjects (crossover design). The mean difference in homocysteine concentration after methionine loading between the two diets was 1.3 [confidence interval (CI) 95%-1.0-3.6] mumol/L which demonstrates that a special low protein diet is not essential in the performance of the methionine loading test. We also observed that 3 weeks after the first methionine loading test, fasting serum concentration of folate was higher and vitamin B12 concentration was lower.

Adult↗

Is hyperhomocysteinaemia a risk factor for recurrent venous thrombosis?

Several studies have shown a relation between hyperhomocysteinaemia and arterial vascular disease. We looked at the association between hyperhomocysteinaemia and venous thrombosis which could be clinically important as hyperhomocysteinaemia is easily corrected by vitamin supplementation. We studied 185 patients with a history of recurrent venous thrombosis and 220 controls from the general population. Homocysteine concentrations were measured before and 6 h after oral methionine loading. We defined hyperhomocysteinaemia as the homocysteine concentration above the fasting or the postmethionine value found for the 90th percentile of the controls. Of the 185 patients with recurrent thrombosis, 46 (25%) had fasting homocysteine concentrations above the 90th percentile or the controls (odds ratio is 3.1 [1.8-5.5]). After adjustment for age, sex, and menopausal status the odds ratio was 2.0 (1.5-2.7). Similar results were found for the post-methionine value (unadjusted odds ratio 3.1 [1.7-5.5], adjusted 2.6 [1.9-3.5]). Hyperhomocysteinaemia is a common risk factor for recurrent venous thrombosis and can lead to a two-fold or three-fold increase in risk.

Adult↗

Severe immunodeficiency in patients treated with fludarabine monophosphate.

Fludarabine monophosphate (FAMP) has been shown to be highly effective against low-grade malignant B-cell lymphoproliferative diseases. Because some opportunistic infections were observed in patients treated with FAMP, we investigated the influence of this drug on several parameters of immunocompetence. For 17 consecutive patients treated with FAMP for CLL or low-grade malignant lymphoma we studied T-cell subpopulations during and after therapy by flow cytometry and our findings were correlated with the clinical course of their disease. A pronounced decrease in the various T-cell subpopulations was seen in all cases, that for CD4+ cells was still present 11-13 months after the end of the therapy. In 7 patients a severe opportunistic infection developed; the outcome was fatal in 2 cases. Only 5 patients did not experience any serious infection. These results show that FAMP therapy in a dose of 25 mg/m2/day for 5 d every 4 weeks might be too toxic for patients with very advanced disease. However, in view of the efficacy of FAMP, the possibility of less intensive schedules for these advanced cases should be explored.

Adult↗

Mitoxantrone, teniposide, chlorambucil and prednisone (MVLP) for relapsed non-Hodgkin's lymphoma. The impact of advanced age and performance status.

Fifty-seven patients with relapsed non-Hodgkin's lymphoma (NHL) of low, intermediate and high-grade malignancy were treated with mitoxantrone, teniposide (Vm26), chlorambucil (Leukeran) and prednisone (MVLP). The median age was 71 years; none of the patients was excluded due to poor performance status (PS). Out of 44 patients with PS (according to WHO) < or = 2, 38 responded with a median progression free survival (PFS) of 21.5 months. Of 13 patients with PS > 2, 6 responded with a median PFS of 8.2 months. Haematopoietic toxicity was related to PS rather than to dose intensity or bone marrow involvement. Three patients died within a short time due to toxicity; another two died later as a result of cardiac failure probably due to accumulated toxicity of adriamycin and mitoxantrone. MVLP chemotherapy is effective and feasible and has only moderate toxicity in patients with relapsed NHL and PS < or = 2, despite advanced age.

Adult↗

Hyaline-vascular type Castleman's disease with concomitant malignant B-cell lymphoma.

This case report describes a patient with localized hyaline-vascular (H-V) type Castleman's disease with concomitant malignant B-cell lymphoma. Malignant lymphoma has been described in association with multicentric type Castleman's disease, but not in association with the localized H-V type. Evidence for a relation between the two lesions in this patient by means of histologic, flow-cytometric, cytogenetic and gene rearrangement studies was not found.

Adult↗

The effect of anticoagulants on the size of platelets in blood smears in the course of time.

In this study we measured platelet size in blood smears using the Kontron Mop Videoplan (Kontron Electronic Group, Weesp, Holland). The blood smears were prepared at different times after phlebotomy; samples were collected in three different anticoagulants and 100 consecutive platelets were measured in each smear. A number of platelet parameters were determined, some of which were based on the log normal distribution of the platelet area. We found that the size of platelets in blood smears is also dependent on the time after phlebotomy and the anticoagulant used. This may be important for the comparison of platelet areas, a characteristic of various disorders. Our data indicate that the optimal interval after phlebotomy for preparation of blood smears is 2-5 min.

Anticoagulants↗

Primary extranodal and nodal non-Hodgkin's lymphoma. A survey of a population-based registry.

In a population-based registry, there were 580 patients with non-Hodgkin's lymphoma (NHL); 236 had primary extranodal lymphoma (41%). The initial localization of the primary extranodal lymphomas varied markedly, although 36% were primary gastrointestinal lymphomas. Histological classification was performed by a regional panel of pathologists according to the Kiel Classification and the International Working Formulation. Twelve per cent of the patients with nodal NHL had a localized disease in contrast to 40% with primary extranodal NHL. Low grade lymphomas were encountered in 30 and 10% of the patients with primary nodal and extranodal NHL, respectively. Recurrence-free survival rate for patients with localized low-grade malignancy and disseminated intermediate grade NHL is significantly better for extranodal lymphoma than for nodal NHL. Patients with disseminated high-grade extranodal NHL had the worst prognosis of all. We conclude that primary nodal and primary extranodal lymphomas should be considered as distinctive and separate entities.

Adolescent↗