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G Vreugdenhil

Publications and source records attributed to G Vreugdenhil.

At least 19 recordsLinked to original sources
PubMed2006

[Sore throat and a swollen neck: Lemierre's syndrome until proven otherwise].

Physicians seldom prescribe antibiotics to patients presenting with a combination of sore throat and feelings of malaise. However, this restrictive regimen may have a downside. Two patients, men aged 23 and 19 years, respectively, with pharyngitis developed a life-threatening syndrome following a Fusobacterium throat infection. They suffered from Lemierre's syndrome, referred to in recent literature as the 'forgotten disease'. The second patient recovered uneventfully after prompt intravenous antibiotic treatment. The first, however, succumbed following overwhelming multiple organ failure. A classical case of Lemierre's syndrome is characterised by bacterial embolisation from a clogged internal jugular vein following a sore throat. Spread of organisms may lead to sepsis and organ failure. The main pathogen is Fusobacterium necrophorum. Early recognition is essential, since prompt antibiotic treatment is usually effective. This syndrome should be suspected until proven otherwise in any patient with signs of pharyngitis, a painful swollen neck and pulmonary symptoms.

Adult↗
PubMed2006

Randomised study of sequential versus combination chemotherapy with capecitabine, irinotecan and oxaliplatin in advanced colorectal cancer, an interim safety analysis. A Dutch Colorectal Cancer Group (DCCG) phase III study.

BACKGROUND: Results on overall survival in randomised studies of mono- versus combination chemotherapy in advanced colorectal cancer patients may have been biased by an imbalance in salvage treatments. This is the first randomised study that evaluates sequential versus combination chemotherapy with a fluoropyrimidine, irinotecan and oxaliplatin. PATIENTS AND METHODS: A total of 820 patients were randomised between first-line capecitabine, second-line irinotecan and third-line capecitabine + oxaliplatin (arm A) versus first-line capecitabine + irinotecan, and second-line capecitabine + oxaliplatin (arm B). The primary end point was overall survival. We present the results of an interim analysis on the safety data in the first 400 patients. RESULTS: In first-line the incidence of grade 3-4 diarrhoea, nausea, vomiting and febrile neutropenia was significantly higher in arm B. However, when toxicity over all lines was considered only grade 3 hand-foot syndrome occurred more frequently in arm A (12% versus 6%, respectively, P = 0.041). The incidence of cardiovascular toxicity was low. In two out of five patients with sudden death (one in arm A, four in arm B) cardiovascular risk factors were present. CONCLUSIONS: Both treatment arms had an acceptable safety profile. These data imply that the results on survival will be the major determinant for the selection of either strategy. Capecitabine plus irinotecan appears to be a feasible first-line treatment for patients with advanced colorectal carcinoma.

Adult↗
PubMed2006

Chronic idiopathic thrombocytopenic purpura: present strategy, guidelines and new insights.

Idiopathic thrombocytopenic purpura (ITP) is an immune-mediated thrombocytopenia. The diagnosis is made after exclusion of other secondary causes of thrombocytopenic disorders. The primary treatment goal is to prevent severe bleeding rather than achieve normal platelet counts. In adults ITP usually has an insidious onset and chronic course. Although ITP is a relatively common haematological disorder, there are important unresolved issues in its management, especially for chronic refractory ITP patients. New therapeutic agents have changed strategies for ITP treatment. This article reviews the treatment indications and options of chronic ITP in adults in the literature and compares them with the treatment indications and treatment options used by the Dutch internist.

Adult↗
PubMed2005

The prognosis of patients with local recurrence more than five years after breast conservation therapy for invasive breast carcinoma.

AIMS: The increasing use of breast-conserving therapy (BCT) and the rising incidence and improved prognosis of early breast are causing a substantial increase in the absolute number of patients with a late local recurrence following BCT. This study examined the characteristics and the prognosis of patients with a local recurrence occurring more than 5 years after BCT. METHODS: In the period 1982-1997, 3280 patients with invasive breast cancer underwent breast-conserving therapy in one of the eight community hospitals in the South-eastern part of The Netherlands. Of these patients, 98 developed a local recurrence in the breast more than 5 years after BCT. RESULTS: Eighty-five of the 98 recurrences were invasive, 12 were purely in situ and for one patient this information was not available. The 5 years distant recurrence-free survival rate of 85 patients with a late invasive local recurrence was 68% (95% confidence interval [CI], 56-80) and significantly better than the rate of 41% (95% CI, 33-48) in an existing cohort of 173 patients with invasive recurrence within 5 years after BCT (p=0.007). Local excision of the recurrence was followed by a significantly lower local control rate than salvage mastectomy (50 vs 89%; p=0.004). CONCLUSION: The prognosis of patients with a local recurrence more than 5 years after BCT is significantly better than of patients with local recurrence within 5 years after BCT.

Adult↗
PubMed2005

Adjuvant treatment for elderly patients with stage III colon cancer in the southern Netherlands is affected by socioeconomic status, gender, and comorbidity.

BACKGROUND: Adjuvant 5-fluorouracil-based chemotherapy significantly decreases mortality among patients with stage III colon cancer, but is less prescribed with rising age. We were interested in the pattern of adjuvant treatment and possible effects on survival among elderly patients. PATIENTS AND METHODS: All resected patients aged 65-79 with stage III colon carcinoma, diagnosed between 1995 and 2001 in the Comprehensive Cancer Centre South registry area in the Netherlands were included (n=577). We examined determinants of receipt of adjuvant chemotherapy and their relation to survival. RESULTS: The proportion of elderly patients receiving adjuvant chemotherapy increased from 19% in 1995 to 50% in 2001, but a large inter-hospital variation remained. In a multivariable analysis, females [odds ratio (OR) 0.5, P=0.006], patients with comorbidity [OR 0.5, P=0.005], and patients with a low socioeconomic status [OR 0.5, P=0.02] received less adjuvant therapy. Between 1995 and 2001 survival of elderly patients improved (hazard ratio 0.8, P=0.04). CONCLUSION: Although an increasing proportion of elderly patients with colon cancer are treated with adjuvant chemotherapy, many elderly patients still do not receive this treatment. As expected, receipt of adjuvant treatment decreased in the presence of comorbidity, but the clinical rationale for undertreatment of women and patients with low socioeconomic status is not clear.

Age Factors↗
PubMed2004

High-dose dexamethasone as a first- and second-line treatment of idiopathic thrombocytopenic purpura in adults.

The current first-line choice of treatment of idiopathic thrombocytopenic purpura (ITP) in adults, prednisone, is effective but has many side effects. Furthermore, reduction of the dose leads to a relapse of ITP in a majority of cases. Courses of high-dose dexamethasone (HD) aim to avoid these problems. We treated 36 patients with newly diagnosed or recurrent ITP with an 8-day course of HD, with a peak dose of 40 mg/day. The courses were repeated up to a maximum of six courses, with a 28-day interval. Acute and chronic effects of HD on platelet counts were observed, as well as side effects. HD led to an acute response (rise of platelet count to a level above 50 x 10(9)/l) in 83%. When HD was given as a first-line treatment, 59% of patients were still in remission after 31 months. When HD was given as a second-line treatment, 50% of patients were in remission after 5 months, declining to 25% after 54 months. Side effects were frequent but rarely dangerous. In conclusion, acute effects of HD were excellent. Long-term effects of HD as a first-line therapy of ITP were good, but its long-term effects as a second-line therapy were much poorer.

Administration, Oral↗
PubMed2004

Comorbidity has negligible impact on treatment and complications but influences survival in breast cancer patients.

In the present study, we investigated whether age and serious comorbid conditions influence treatment decisions, complications and survival in breast cancer patients. The Eindhoven Cancer Registry records patient, tumour and therapy characteristics of all patients diagnosed with cancer in the southern part of the Netherlands. Additional information on severity of comorbidity and serious complications was collected for a random sample of 527 breast cancer patients (aged 40 years and older). More than 70% of the patients >or=80 exhibited high severity of comorbidity compared to 6% of those aged 40-49 years. Treatment was not influenced by severity of comorbidity. Less than 30% of the breast cancer patients had complications after diagnosis. The number of complications was not related to age or severity of comorbidity. The hazard ratio (HR) of dying for patients with low/moderate severity of comorbidity was 2.4 for those aged 40-69 years and 1.6 for those aged >or=70 years, after adjustment for age, nodal status and treatment. For patients with high severity of comorbidity, the risk of dying was almost three times higher. Older breast cancer patients with serious comorbidity were not treated differently and did not have more complications compared to those without comorbidity, but they exhibited a worse prognosis.

Adult↗
PubMed2004

Human pancreatic duct cells can produce tumour necrosis factor-alpha that damages neighbouring beta cells and activates dendritic cells.

AIMS/HYPOTHESIS: In the human pancreas, a close topographic relationship exists between duct cells and beta cells. This explains the high proportion of duct cells in isolated human islet preparations. We investigated whether human duct cells are a source of TNFalpha-mediated interactions with beta cells and immune cells. This cytokine has been implicated in the development of autoimmune diabetes in mice. METHODS: Human duct cells were isolated from donor pancreases and examined for their ability to produce TNFalpha following a stress-signalling pathway. Duct-cell-released TNFalpha was tested for its in vitro effects on survival of human beta cells and on activation of human dendritic cells. RESULTS: Exposure of human pancreatic duct cells to interleukin-1beta (IL-1beta) induces TNFalpha gene expression, synthesis of the 26,000 M(r) TNFalpha precursor and conversion to the 17,000 M(r) mature form, which is rapidly released. This effect is NO-independent and involves p38 MAPK and NF-kappaB signalling. Duct-cell-released TNFalpha contributed to cytokine-induced apoptosis of isolated human beta cells. It also induced activation of human dendritic cells. CONCLUSIONS/INTERPRETATION: Human pancreatic duct cells are a potential source of TNFalpha that can cause apoptosis of neighbouring beta cells and initiate an immune response through activation of dendritic cells. They may thus actively participate in inflammatory and immune processes that threaten beta cells during development of diabetes or after human islet cell grafts have been implanted.

Apoptosis↗
PubMed2003

Treatment and survival of 38 female breast lymphomas: a population-based study with clinical and pathological reviews.

Breast lymphomas are rare and consensus about their treatment is lacking. A population-based study of 38 breast lymphomas, registered in the databases of two Comprehensive Dutch Cancer Centers from 1981 to 1999, was performed. The median age of all female patients was 65 years (20-92): 25 patients had localized and 13 patients had disseminated lymphoma. The most common type was diffuse large B-cell lymphoma (DLBCL), which accounted for 17 of the localized and 4 of the disseminated cases. Burkitt's lymphoma (BL), three being disseminated, was found in four patients. There were six extranodal marginal zone lymphomas (ENMZL), three being localized. Seven DLBCL and one BL showed additional histological features of mucosa-associated lymphoid tissue (MALT) lymphoma. Localized aggressive lymphomas treated with surgery and/or radiation therapy had relapse rates of 100% and 67%, respectively. Cyclophosphamide, hydroxydaunomycin, vincristine, and prednisone (CHOP)-like chemotherapy with or without local irradiation led to 17% relapses in patients with localized aggressive lymphoma. Median follow-up time was 32 months (0.6-218); 37% of the patients relapsed and 24% had progressive disease. Response to salvage regimens, given to 91% of the patients with recurrent disease, was poor. The 2-year overall survival rate was 63%, 72% for patients with localized disease, and 46% for patients with disseminated lymphoma. The majority of breast lymphomas are localized aggressive lymphomas that should be treated initially with CHOP-like chemotherapy with or without irradiation. The initial choice of treatment is very important because response to salvage regimens is poor.

Adult↗
PubMed2003

Rituximab in the treatment of relapsing idiopathic thrombocytopenic purpura.

About 25 to 30% of patients with idiopathic thrombocytopenic purpura (ITP) are resistant to standard treatment with steroids and splenectomy. In these patients with chronic refractory ITP, there is no proven algorithm for standard care. Recently, the chimeric anti-CD20 monoclonal antibody rituximab was considered as an alternative treatment option in this patient group. We present a patient with frequently relapsing ITP after treatment with prednisone, splenectomy and high-dose dexamethasone. Since he experienced increasing side effects due to the steroids, he was treated with rituximab 375 mg/m2, once weekly for four weeks, resulting in a complete long-lasting response (follow-up seven months).

Antibodies, Monoclonal↗
PubMed2002

[Dutch Institute for Healthcare Improvement guideline, "Treatment of breast cancer"].

The first Dutch evidence-based guideline for the treatment of breast cancer has been developed to realise the optimal care of breast cancer patients in the Netherlands. This was possible due to the close cooperation of the Dutch Institute for Healthcare Improvement [Dutch acronym: CBO] and the Dutch Consultative Committee on Breast Cancer [Dutch acronym: NABON]. A broad, multidisciplinary working group was appointed to develop the guideline. This group consisted of surgeons, radiotherapists, internists, pathologists, a radiologist, a nuclear medicine specialist, a plastic surgeon and a clinical geneticist, all of whom had been given a mandate to represent their respective professional societies. In addition to these medical specialists, there were physiotherapists, oncology nurses, psychologists, staff from comprehensive cancer centres and the Dutch Institute for Healthcare Improvement and representatives from the Dutch Breast Cancer Association. This CBO guideline is divided into seven chapters: local treatment of operable breast cancer, systemic adjuvant treatment, locoregionally advanced disease, follow-up, locoregional recurrence, metastasised disease, and the psychosocial aspects of breast cancer. Although the guideline is not intended as a set of instructions that must be rigidly adhered to, deviations from the guideline must be motivated, principally on the basis of published scientific information. To obtain insight into the actual use of the guidelines 'Screening and diagnostics' and 'Treatment of breast cancer' the work group advocates a nationwide prospective registration of all breast cancer patients, including follow-up. Steps to this end have been undertaken. In this way, the CBO guideline will contribute to a further optimisation of breast cancer care in the Netherlands.

Breast Neoplasms↗
PubMed2001

Tumor growth pattern and thymidine phosphorylase expression are related with the risk of hematogenous metastasis in patients with Astler Coller B1/B2 colorectal carcinoma.

BACKGROUND: The benefit of adjuvant chemotherapy appears to be limited for patients with Astler Coller B1/B2 colorectal carcinoma but may be better in a subgroup of patients with a high recurrence risk. In the current case-control analysis, the authors evaluated whether patients with a high risk of hematogenous metastasis could be identified by means of a thorough histologic and immunohistochemical examination of the resection specimens. METHODS: A database was built for all patients treated in a general teaching hospital for colorectal carcinoma between 1985 and 1995. From this database, all patients with an Astler Coller B1 or B2 tumor who subsequently had developed hematogenous metastases were taken as cases. For each case, three matched controls (age, Astler Coller, year of diagnosis) without metachronous metastases were selected. The resection specimens of cases and controls were blindly examined by two observers for the following: World Health Organization (WHO) classification; differentiation grade; growth pattern; lymphocytic, fibroblastic, and eosinophilic reaction; angioinvasion; number of lymph nodes examined; expression of E-cadherin, vascular endothelial growth factor and thymidine phosphorylase (TP); P53; microvessel density. RESULTS: Twenty-two cases and 65 controls were included in the analysis. Tumor growth pattern and tumor TP expression both independently contributed to recurrence risk. With these 2 variables, 4 subgroups could be identified with a recurrence risk ranging from 0% to 42%. CONCLUSIONS: Tumor growth pattern and degree of TP expression both appear to be related to the recurrence risk. Prospective trials should point out whether these variables can be implemented in the decision making concerning adjuvant chemotherapy.

Biomarkers, Tumor↗
PubMed2001

Risk, severity and predictors of physical and psychological morbidity after axillary lymph node dissection for breast cancer.

The aim of this study was to investigate the nature and severity of the arm complaints among breast cancer patients after axillary lymph node dissection (ALND) and to study the effects of this treatment-related morbidity on daily life and well-being. 400 women, who underwent ALND as part of breast cancer surgery, filled out a treatment-specific quality of life questionnaire. The mean time since ALND was 4.7 years (range 0.3-28 years). More than 20% of patients reported pain, numbness, or loss of strength and 9% reported severe oedema. None of the complaints appeared to diminish over time. Irradiation of the axilla and supraclavicular irradiation were associated with a 3.57-fold higher risk of oedema (odds ratio (OR) 3.57; 95% confidence interval (CI) 1.66-7.69) causing many patients to give up leisure activities or sport. Women who underwent irradiation of the breast or chest wall more often reported to have a sensitive scar than women who did not receive radiotherapy. Women <45 years of age had an approximately 6 times higher risk of numbness of the arm (OR 6.49; 95% CI 2.58-16.38) compared with those > or = 65 years of age; they also encountered more problems doing their household chores. The results of the present study support the introduction of less invasive techniques for the staging of the axilla, sentinel node biopsy being the most promising.

Activities of Daily Living↗
PubMed2000

[Impact of the new guidelines for adjuvant systemic treatment of breast cancer at hospital level].

Recently, the Dutch Society for Medical Oncology published new consensus guidelines for the use of adjuvant systemic treatment in patients with operable breast cancer. We used data of the cancer registry of the Comprehensive Cancer Centre South to predict the change in the number of patients who will be candidates for systemic treatment according to these new guidelines. It was estimated that of all patients with operable breast cancer, 15% should receive chemotherapy, 27% hormonal therapy and 17% a combination of both modalities. Of the patients with negative axillary lymph nodes, one-third will receive adjuvant systemic treatment. Compared with the previous guidelines, the introduction of the new guidelines will cause a 50% increase in the number of patients receiving adjuvant systemic treatment in Dutch hospitals.

Breast Neoplasms↗
PubMed2000

[Adjuvant systemic therapy for patients with resectable breast cancer: guideline from the Dutch National Breast Cancer Platform and the Dutch Society for Medical Oncology].

There is an abundance of evidence that adjuvant systemic therapy with chemotherapy or endocrine therapy results in better survival for all patients with resectable breast cancer. The absolute 10-year survival advantage however varies for the different patient groups. Therefore, for each individual patient the choice of adjuvant therapy must take into account the potential benefits and the possible side effects. A group of medical oncologists from the Dutch National Breast Cancer Platform (NABON) and the Dutch Society for Medical Oncology (NVMO) prepared a guideline for the treatment of patients with early resectable breast cancer. The criterium for choosing adjuvant systemic therapy for the individual patient is an expected increase in 10-year survival of 5% or more. In the guideline a difference is made between patients with and without axillary lymph node metastasis. In patients with axillary lymph node metastasis the choice for adjuvant systemic therapy depends on the following prognostic factors: menopausal status, age, and the presence of estrogen and progesterone receptors in the tumour. In patients without axillary lymph node metastasis the choice depends also on the following prognostic factors: the size of the tumour, the mitotic activity index, or the histopathologic grade of differentiation.

Adult↗
PubMed1999

Recombinant human erythropoietin improves health-related quality of life in patients with rheumatoid arthritis and anaemia of chronic disease; utility measures correlate strongly with disease activity measures.

Treatment with recombinant human erythropoietin (r-hu-Epo) in patients with rheumatoid arthritis (RA) and anaemia of chronic disease (ACD) resulted in improvement of both anaemia and disease activity. Utilities represent a generic and comprehensive quality of life measure, capable of integrating domain-specific information into one overall value which a patient assigns to his state of health. Therefore, the effect of r-hu-Epo on quality of life was studied by measuring utilities, derived from the rating scale and standard gamble, in a 52-week placebo-controlled randomised double-blind study with r-hu-Epo in 70 patients with active RA and ACD. Furthermore, the relation between anaemia as assessed by haemoglobin levels (Hb), disease activity as assessed with the Disease Activity Score (DAS), and utilities was investigated. Compared to the placebo group, significant improvement of Hb (P < 0.001), DAS (P = 0.01) and rating scale utilities (P = 0.002), but not of standard gamble utilities, was observed in the Epo group. Rating scale utilities correlated strongly with DAS (r = -0.47, P < 0.01), Hb (r = 0.37, P < 0.01) and changes in both DAS (r = -0.74, P < 0.01) and Hb (r = 0.44, P < 0.01). Both DAS and Hb contributed significantly to the variance in rating scale utilities (21% and 3% respectively) and to changes in rating scale utilities (43% and 3% respectively). Standard gamble utilities correlated less well with clinical disease variables than rating scale utilities did. These results indicate, that r-hu-Epo improves utility-derived health-related quality of life, most probably by improving both disease activity and anaemia. Utilities, particularly rating scale utilities, correlated well with conventional disease activity variables and proved sensitive to change. Utilities may be a useful tool for investigating quality of life in RA-patients.

Adult↗
PubMed1999

Characteristics of recovery from the euthyroid sick syndrome induced by tumor necrosis factor alpha in cancer patients.

Cytokines have been implicated in the pathogenesis of the euthyroid sick syndrome. Isolated limb perfusion (ILP) with recombinant human tumor necrosis factor alpha (rTNF) and melphalan in patients with melanoma or sarcoma is accompanied by high systemic TNF levels. We examined the prolonged effects (7 days) of ILP on thyroid hormone metabolism with respect to induction and recovery of the euthyroid sick syndrome in six cancer patients. After ILP, when the limb is reconnected to the systemic circulation, leakage of residual rTNF resulted in systemic peak levels at 10 minutes postperfusion followed by a parallel increase in plasma interleukin-6 (IL-6) and cortisol, with maximum levels at 4 hours (P < .05). A rapid decrease was observed at 5 minutes for plasma triiodothyronine (T3), reverse T3 (rT3), thyroxine (T4), and thyroxine-binding globulin (TBG) (P < .05), whereas free T4 (FT4) and T3-uptake showed a sharp increase, with peak levels at 5 minutes (P < .05). T3, T4, and TBG levels remained low until 24 hours after ILP In contrast, rT3 increased above pretreatment values to maximum levels at 24 hours (P < .05). Plasma thyrotropin (TSH) showed an initial decrease at 4 hours postperfusion (P < .05) but exceeded pretreatment values from day 1 to day 7 (by +94%+/-43% to +155%+/-66%, P < .05), preceding the recovery of T4 and T3 levels. T3 and rT3 returned to initial values at day 4. T4 and TBG levels recovered at day 2. T4 exceeded basal values at days 5 to 7 (P < .05). It is concluded that ILP with rTNF induces a euthyroid sick syndrome either directly or indirectly through other mediators such as IL-6 or cortisol. The recovery from this euthyroid sick syndrome is, at least in part, TSH-dependent, since the prolonged elevation of TSH values preceded and persisted during the normalization of T3 and the elevation of T4 levels. This biphasic pattern of induction of and recovery from the euthyroid sick syndrome may be a general feature of nonthyroidal disease. The euthyroid sick syndrome should be interpreted not only in relation to the presence of nonthyroidal diseases but also in relation to the recovery from these diseases.

Aged↗