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Biomedical subjects

J Hermans

Publications and source records attributed to J Hermans.

At least 163 records · Page 9Linked to original sources

Effect of resumption of second line drugs in patients with rheumatoid arthritis that flared up after treatment discontinuation.

OBJECTIVE: To assess the effect of resumption of second line drugs in patients with rheumatoid arthritis (RA) that flared after treatment discontinuation. METHODS: RA patients were studied whose RA flared up after discontinuation of second line treatment while being in remission and who received a second course of the drug. Disease activity parameters were prospectively assessed at the time of treatment discontinuation, during the period when the disease flared up, and three months thereafter. Furthermore the medical charts were reviewed at 12 months after treatment resumption. RESULTS: There were 51 patients included in the study: 25 patients treated with antimalarial drugs, 10 with parenteral gold, four with d-penicillamine, eight with sulphasalazine, two with azathioprine, and two with methotrexate. Disease activity parameters showed significant improvement within three months of treatment resumption, but remained significantly worse when compared with that measured before treatment discontinuation. Within three months 47% of the patients fulfilled 20% response criteria. Disease activity 12 months after treatment resumption was considered to be absent in 35%, mild in 43%, and moderate or active in 22% of the patients. In four (8%) patients the resumed treatment was stopped because of lack of efficacy. Side effects were recorded in four patients, which did not result in treatment discontinuation. CONCLUSIONS: Resumption of second line drugs in RA patients whose disease flared up after discontinuation of treatment is effective and safe in most patients. Half of the patients responded within three months after resumption of the second line drug.

Acute Disease↗

Intelligence indices in people with a high/low risk for developing Huntington's disease.

Intelligence in 20 presymptomatic subjects with an increased risk (> 95%) for carrying the gene for Huntington's disease (HD) was studied in a prospective, case-control, single blind study. No significant differences between the groups were detected for intelligence indices and subtest scores (Wechsler Adult Intelligence Scale). The high level of the performance IQ and the significant discrepancy between performance IQ and verbal IQ found in both the high risk and the low risk groups contrasted with our expectations based on anamnestic information, general clinical opinion, and the results of previously conducted studies. We propose that psychosocial circumstances could explain the test results and discuss the consequences of our findings for clinical genetics practice.

Adult↗

Diversity and prevalence of somatic mutations in the thyrotropin receptor and Gs alpha genes as a cause of toxic thyroid adenomas.

A total of 33 different autonomous hot nodules from 31 patients, originating mainly from Belgium, were investigated for the presence of somatic mutations in the TSH receptor and Gs alpha genes. This constitutes an extension of our previous study, including the first 11 nodules of the series. The complete coding sequence of the TSH receptor gene and the segments of Gs alpha known to harbor mutations impairing guanosinetriphosphotase activity were studied by direct sequencing of genomic DNA extracted from the nodules. DNA from the juxtanodular tissue or peripheral white blood cells was analyzed in all patients to confirm that the mutations identified were somatic. Twenty-seven mutations (82%) were found in the TSH receptor gene, affecting a total of 12 different residues or locations. All these mutations but 2 (see below) have been identified previously as activating mutations. Only 2 mutations were found in Gs alpha (6%). In 4 nodules, no mutation was detected. Five residues (Ser281, Ile486, Ile568, Phe631, and Asp633) were found mutated in 3 or 4 different nodules, making them hot spots for activating mutations. Phe631 and Asp633 belong to a cluster of 5 consecutive residues (629-633) in the N-terminal half of transmembrane segment VI; which harbor together 44% of the mutations identified in this cohort. Two novel mutations were identified: a point mutation causing substitution of Phe for Leu at position 629 (L629F); and a deletion of 12 bases removing residues 658-661 at the C-terminal portion of exoloop 3 (del658-661). When tested by transfection in COS-7 cells, both mutant receptors display increase in constitutive stimulation of basal cAMP accumulation. Although it is still capable of binding TSH, the del658-661 mutant has completely lost the ability to respond to the stimulation by the hormone. Our results demonstrate that, in a cohort of patients from a moderately iodine deficient area, somatic mutations increasing the constitutive activity of the TSH receptor are the major cause of autonomous hot nodules.

Adenoma↗

Does magnetic resonance imaging make a difference for patients with musculoskeletal sarcoma?

MR imaging has had an unparalleled impact on the treatment of patients with musculoskeletal sarcoma. Basically, the high accuracy of local staging has made the introduction of reconstructive and limb salvage procedures instead of amputation of disarticulation available to the majority of patients with musculoskeletal sarcoma. Pre-operative work-up with MRI is not only more accurate, but also much faster and cheaper than the conventional work-up. Staging is the single most important reason for performing MR imaging in patients with musculoskeletal tumours. The impact of MR specificity is less dramatic but the benefit to the patient is an increased safety margin. When diagnostic errors with devastating consequences are made nowadays, it is usually because the proper protocol has not been followed. A patient with a potentially malignant, or equivocal, musculoskeletal mass deserves to have a combined radiographic-MRI examination prior to invasive procedures. MRI does not currently have a major impact on chemotherapy decisions and colour Doppler ultrasound has a higher accuracy than MRI. However, selected cases, i.e. intraosseous tumours, dynamic Gd-enhanced MRI, can replace colour Doppler ultrasound.

Adult↗

Late prednisone withdrawal in cyclosporine-treated kidney transplant patients: a randomized study.

Prednisone in combination with cyclosporine and/or azathioprine is commonly used after kidney transplantation to prevent graft rejection. Long-term use of prednisone can give rise to multiple side effects and morbidity. This randomized study was conducted to find out if prednisone could be withdrawn in recipients at least 1 yr after kidney transplantation. Eighty-four such recipients of a cadaveric kidney with stable renal function on cyclosporine and prednisone were randomized to continue prednisone (N = 42) or to withdraw prednisone in a 2-month period (N = 42). The main end point was the percentage of successful prednisone withdrawal. Both groups were compared for the incidence of infections and cardiovascular risk factors and for the incidence and cause of deterioration of renal function. All patients had a 14-month follow-up. In 67% (N = 28) of the patients, prednisone could be withdrawn successfully. Acute rejection was the main cause of withdrawal failure (N = 11, 26%). No grafts were lost due to rejection. In the prednisone withdrawal group, a tendency was noted for a lower incidence of infections (difference: 17%; 95% confidence interval [CI]: -4% to 37%). After withdrawal, less antihypertensive drugs were necessary to control hypertension (difference: 0.5 drugs/patient; 95% CI: -0.9 to -0.1) and 35% less patients (23 of 41 versus nine of 42) needed cholesterol-lowering drugs (95% CI: -54% to -15%). A reduction of the frequency of patients with Type II diabetes mellitus was found (difference 10%; 95% CI: -24% to 5%) with a decrease of glycosylated hemoglobin (difference: 0.4 mmol/L; 95% CI: 0.1 to 0.8). Disappearance of moonface was found in 25% of the patients. Elective withdrawal of prednisone > 1 yr after postmortal kidney transplantation can be accomplished safely provided that patients are controlled frequently. Beneficial effects were found regarding hypertension, hypercholesterolemia, hyperglycemia, and appearance.

Adult↗

Usefulness of radiography in differentiating enchondroma from central grade 1 chondrosarcoma.

OBJECTIVE: The purpose of this study was to evaluate clinical symptoms and radiographic features that allow radiologists to differentiate between enchondroma and central grade 1 chondrosarcoma. Such differentiation is important because of differences in management. MATERIALS AND METHODS: Clinical symptoms and location and size of 35 enchondromas and 43 central grade 1 chondrosarcomas were analyzed. Radiographic features were assessed independently by three observers. The chi-square test and linear discriminant analysis were used to identify features with discriminating strength. Kappa values were calculated to validate the consistency of observations among observers. A consensus diagnosis made by histology and long-term follow-up was used as the standard. RESULTS: No statistically significant correlation was found between clinical symptoms and the benign or malignant nature of the neoplasms. Grade 1 chondrosarcomas were more likely to be found in the axial skeleton and in flat bones. Also, chondrosarcomas were significantly larger than enchondromas (p < .001). Ill-defined margins and lobulated contours were the only morphologic features seen on radiographs that allowed significant discrimination (p = .004 and .009, respectively). An optimal combination of four radiographic features still left 72 of the 78 lesions with a 10-90% probability of malignancy, indicative of poor discriminating power. Kappa values generally showed poor to fair agreement. CONCLUSION: Location in the axial skeleton and size greater than 5 cm are the most reliable predictors of central grade 1 chondrosarcoma. Morphologic features seen on radiographs and clinical symptoms do not improve the ability to differentiate between enchondromas and central grade 1 chondrosarcomas.

Adolescent↗

Development of a "Myeloma Risk Score" using a population-based registry on paraproteinemia and myeloma.

Diagnostic systems for monoclonal gammopathies use bone marrow and X-ray examinations to exclude multiple myeloma (MM). Data from a population-based registry of unselected patients with paraproteinemia indicate that these tests are often done only when MM is suspected. We used 441 randomly selected patients to develop a simple four point "Myeloma Risk Score" based on two readily available laboratory tests. One point was given for paraprotein concentration > or = 10 g/l, one point for IgG and IgA, and two points for IgD and light chains only. A score of 0 or 1 indicated a low risk for MM, with scores of 2 and 3 signifying high risks. Sensitivity, specificity, positive and negative predictive value (PV) for the Myeloma Risk Score in the training sample were 92%, 88%, 79%, and 96% respectively. Extrapolating these results to a larger cohort showed that 90% of patients with a monoclonal gammopathy could be classified correctly as having MM or a non-myeloma condition. The Myeloma Risk Score can identify patients with a paraproteinemia at risk for MM, and who are therefore candidates for bone marrow and X-ray examination.

Biomarkers, Tumor↗

Dutch normal-pressure hydrocephalus study: prediction of outcome after shunting by resistance to outflow of cerebrospinal fluid.

The authors examined whether measurement of resistance to outflow of cerebrospinal fluid (Rcsf) predicts outcome after shunting for patients with normal-pressure hydrocephalus (NPH). In four centers 101 patients (most of whom had idiopathic NPH) who fulfilled strict entry criteria underwent shunt placement irrespective of their level of Rcsf obtained by lumbar constant flow infusion. Gait disturbance and dementia were quantified by using an NPH scale and the patient's level of disability was assessed by using the modified Rankin scale (mRS). In addition the Modified Mini-Mental State Examination was performed. Patients were assessed prior to and 1, 3, 6, 9, and 12 months after surgery. Primary outcome measures were based on differences between the preoperative and last NPH scale scores and mRS grades. Improvement was defined as a change measuring at least 15% in the NPH scale score and at least one mRS grade. Intention-to-treat analysis of all patients at 1 year yielded improvement for 57% in NPH scale score and 59% in mRS grade. Efficacy analysis, excluding serious events and deaths that were unrelated to NPH, was performed for 95 patients. Improvement rose to 76% in NPH scale score and 69% in mRS grade. Six cut-off levels of Rcsf were related to improvement in NPH scale score using two-by-two tables. Positive predictive values were approximately 80% for an Rcsf of 10, 12, or 15 mm Hg/ml/minute, 92% for an Rcsf of 18 mm Hg/ml/minute, and 100% for an Rcsf of 24 mm Hg/ml/minute. Negative predictive values were low. More important was the highest likelihood ratio of 3.5 for an Rcsf of 18 mm Hg/ml/minute. Extensive comorbidity was a major prognostic factor. Measurement of Rcsf reliably predicts outcome if the limit for shunting is raised to 18 mm Hg/ml/minute. At lower Rcsf values the decision depends mainly on the extent to which clinical and computerized tomography findings are typical of NPH.

Aged↗

Accuracy of the Jamshidi trocar biopsy in the diagnosis of bone tumors.

Obtaining a histologic diagnosis is crucial in patients presenting with a tumor or a tumorous condition of the bone. The incisional surgical and the closed trocar biopsy are the most frequently used techniques for obtaining a representative tissue sample for histologic evaluation. This study reports on the reliability of 270 Jamshidi trocar biopsies performed on 258 patients with osseous tumors and tumorlike lesions. All patients were evaluated clinically and radiographically by a team consisting of an orthopaedic surgeon, a radiologist, and a surgical pathologist. In nearly all cases the biopsy and the resection were performed by the same orthopaedic surgeon. The biopsy site was determined in accordance with the planned subsequent resection surgery. Overall, an accurate diagnosis could be reached in 90.7% of the total number of 270 Jamshidi biopsies and in 95% of the 258 patients. The failure rate of the 270 biopsies was 9.3%. No specific contraindications with regard to the kind of lesion were found. Except for the pelvis, the localization of the lesion did not influence the rate of success. The high accuracy of the trocar biopsy, combined with the advantages of this technique over the incisional surgical biopsy, makes it a safe, fast, and adequate technique for obtaining a histologic sample of a bone tumor.

Adolescent↗

Continuous double loop closure: a new technique for repair of laparotomy wounds.

BACKGROUND: Wound dehiscence after midline laparotomy is a life threatening complication, most frequently caused by sutures cutting through the fascia. Increasing the strength of the sutured wound could prevent wound rupture. METHODS: In an experimental study in the rat, the simple continuous suture (SCS), loop suture (LS), interrupted double loop closure and continuous double loop closure (CDLC) techniques were evaluated. Dehiscence pressure and volume were measured after closing a standard laparotomy. RESULTS: Laparotomies closed with the newly developed CDLC technique could withstand by far the highest intra-abdominal pressure before dehiscence (P < 0.0002). Wounds closed with this technique remained well approximated regardless of the intra-abdominal pressure, unlike wounds closed with the frequently used SCS and LS methods. CONCLUSION: In all animals sutured with the CDLC technique the intact abdominal wall ruptured lateral to the wound at dehiscence pressure, indicating that the bursting strength of the sutured wound was higher than that of the intact abdominal wall.

Animals↗

Loss of heterozygosity at 7q31 in breast cancer: results from an International Collaborative Study Group. The Breast Cancer Somatic Genetics Consortium.

Loss of heterozygosity (LOH) at 7q31 has been claimed to occur in over 80% of all breast cancers and to be of prognostic significance. This would make this genetic alteration the most common event observed in breast cancer to date. Others, however, have been unable to confirm this high incidence. In this multicenter study, we have complied LOH scorings for three polymorphic markers for 7q31-q32 in 683 breast tumors. Although some significant differences between centers existed, no center reported more than 40% LOH, and the average rate was 19%. Disease-free and overall survival of the patients whose tumors carried LOH at 7q31 did not differ significantly from those patients whose tumors showed retention of heterozygosity at 7q31. In a double-blind scoring of a subset of the raw data, an average discordant rate of LOH scoring of 12% was observed. While startling in itself, this was unable to explain the variation among centers, nor the difference with the initially reported high rate of LOH. We conclude that LOH at 7q31 is not important as a genetic alteration in breast cancer as originally suggested, nor a strong determinant of disease outcome.

Breast Neoplasms↗

Chronic splanchnic ischaemia: is tonometry a useful test?

OBJECTIVE: To find out if gastric tonometry is of sufficient accuracy to diagnose chronic splanchnic syndrome. DESIGN: Prospective open study. SETTING: University hospital, The Netherlands. SUBJECTS: 10 patients in whom chronic splanchnic syndrome had been suspected, and in 5 of whom it was subsequently confirmed. INTERVENTION: Standardised measurement of intramucosal gastric pH (tonometry) and multiplane angiography of the abdominal aorta and splanchnic arteries. MAIN OUTCOME MEASURE: Correlation between intramucosal gastric pH and angiographic and clinical findings. RESULTS: The mean basal pH preoperatively was 7.48 among 5 patients subsequently found to have splanchnic syndrome (group 1) and 7.41 among the 5 who did not (group 2). Those in group 1 all had extensive three vessel disease with stenoses of 70% or more in at least two of the three splanchnic arteries. The 5 patients in group 2 had no clinically important stenoses in either the coeliac or the superior mesenteric artery; 4 had occlusions of the inferior mesenteric artery. CONCLUSION: Gastric tonometry is of no use in the diagnosis of chronic splanchnic syndrome.

Adult↗

The use of serum eosinophil cationic protein (ECP) in the management of steroid therapy in chronic asthma.

BACKGROUND: Corticosteroid therapy has become the mainstay in the treatment of asthma. However, the risk-benefit balance in the patient calls for assessment of the state of inflammation in the airways. In this respect serum eosinophil cationic protein (ECP) might be a marker, which can easily be measured in a clinical setting. Studies have indicated a relation between level of serum ECP and activity and severity in asthma. OBJECTIVE: To investigate the feasibility to guide steroid therapy on the basis of the level of serum ECP in patients with chronic asthma. METHODS: Twenty adult patients on maintenance inhaled steroid therapy visited the chest clinic once every 2 months over a 12-month period. At each visit a short history, blood sample for ECP and number of eosinophils, baseline spirometry, and histamine inhalation provocation test (PC20) were obtained. On the basis of level of ECP, adjustments in daily dose of steroids were considered. Data were compared with those of a previous 6-month ECP evaluation study in these same patients. RESULTS: In 10 patients mean dose of inhaled steroids was decreased > or = 25%. ECP rose slightly (antilogged mean from 9.06 to 11.8 micrograms/L) and lung function decreased slightly (mean FEV1 %predicted from 85.5 to 81.6). In seven patients mean dose of inhaled or oral (n = 2) steroids was increased > or = 25%. In this group ECP decreased but remained elevated at > or = 20 micrograms/L (antilogged mean from 30.5 to 25.6 micrograms/L) and lung function improved (mean FEV1 %predicted from 67.2 to 74.5). In both groups patients' scores of asthmatic well-being increased significantly, and PC20 did not show a trend. Exacerbation rate remained the same in the decreased and the no change group (n = 3, in which no substantial change in steroid dose occurred), but was reduced by about 50% in the increased group. CONCLUSION: From this observational study it is concluded that adjusting steroid therapy guided by serum ECP-level may be helpful in tailoring asthma treatment.

Administration, Inhalation↗

Renal granulomas in systemic vasculitis. EC/BCR Project for ANCA-Assay Standardization.

Renal granulomas are a relatively infrequent finding in the kidney biopsy. They have been described in a number of syndromes such as Wegener's granulomatosis, anti-GBM glomerulonephritis, and sarcoidosis, and are commonly believed to be indicative of a fulminant clinical course. In leading textbooks, diverse definitions of renal granulomas are presented, which has led to controversies in identifying them. This, in combination with their rare occurrence, makes it difficult for the general pathologist to identify them. We present the clinical data of 16 patients with renal granulomas, from a total group of 157 patients with systemic vasculitis. Their renal functioning was not significantly different from the other 141 patients in whose renal biopsies renal granulomas were present. Furthermore, we present two practical definitions for the recognition of renal granulomas in the kidney biopsy, and we show a number of examples of their various histopathological shapes.

Adult↗

[Autonomous thyroid adenoma. Value of thallium scintigraphy and pathology].

Clinical, biological, scintigraphic (99mTc, 123I, 201Tl) and histological data were reviewed in 90 patients operated for autonomous adenomas (hot nodules). Analysis of the data gave the following results: 74.4% of the nodules were solitary and 25.6% occurred in a multinodular goiter (MNG). Hyperthyroidism (FT3-, FT4-, TSH < 0.1) was present in 44% of solitary nodules and in 15% of MNG. 16.6% of patients were euthyroid, and 22.2% had a TSH < 0.1 and normal free hormones. The 201 Tl scintigraphy, performed instead of the administration of exogenous TSH, showed and uptake of Tl in the remainder of the thyroid. Four types of 201Tl uptake were observed in the pathological lobe: type 1: homogeneous uptake: type 2: heterogeneous uptake and hyperfixation in the nodule; type 3: faint uptake and hypofixation in the nodule; type 4: faint and very heterogeneous uptake. Histological analysis of the nodules showed 32.2% of follicular adenomas, 25.6% of MNG and 42.2% of colloid nodules. Among these lesions, 70% showed histological signs of hypermetabolism (resorption vesicles ...). Multivariate analysis of these data clearly demonstrates the need to redefine the clinical, biological, scintigraphic and histological concepts of autonomous adenomas. On the other hand, 91.6% of follicular adenomas show a type 2 Thallium uptake (22/24). On basis of these results, we prefer to operate these patients rather than to treat them by 131I or by percutaneous injection of ethanol.

Adenoma↗

Allogeneic bone marrow transplantation versus autologous stem cell transplantation in multiple myeloma: a retrospective case-matched study from the European Group for Blood and Marrow Transplantation.

A retrospective case-matched analysis was performed comparing 189 myeloma patients treated with allogeneic bone marrow transplantation (allo-BMT) with an equal number of patients who received autologous stem cell transplantation (ASCT). Matching was performed with respect to gender and number of treatment lines before transplantation. The groups were comparable with the exception of median age (43 years for allo-BMT v 49 years for ASCT, P = .0001) and median posttransplant follow-up (46 months for allo-BMT v 30 months for ASCT, P = .0003). The overall survival was significantly better for ASCT than for allo-BMT, with a median survival of 34 months and 18 months, respectively (P = .001). However, this survival advantage was only observed in men, but not in women. The statistically significant survival advantage for ASCT was seen in most subgroups, ie, chemotherapy-responsive patients, patients who had received two or more treatment lines before transplantation, patients in partial remission, patients with an IgG-subtype, patients older than 46 years of age, patients with stage II disease, and patients with a low or high serum-beta-2-microglobulin at diagnosis. The main reason for the poorer survival in allo-BMT patients was higher transplant-related mortality (41% v 13% for ASCT, P = .0001), which was not compensated for by a lower rate of relapse and progression. However, in patients alive at 1 year posttransplant, there was a trend for better long-term survival (P = .09) and significantly better progression-free survival (P = .02) for allo-BMT as compared with ASCT. We conclude that the median survival is superior for ASCT. However, allo-BMT has a lower relapse rate, which results in a similar long-term outcome for both approaches, but a longer follow-up is needed to assess the final outcome.

Acute Disease↗

[Preoperative needle biopsy: an improvement in palpable breast tumors with strong indications for malignancy].

OBJECTIVE: To assess the value of needle core biopsy to replace frozen sections in palpable breast masses highly suspicious for malignancy. DESIGN: Cohort study. SETTING: University Hospital Leiden, the Netherlands. METHOD: In 274 patients with 279 palpable breast masses a needle core biopsy was performed in addition to the triple diagnostic approach (i.e. physical examination, imaging by mammography and ultrasound and cytologic examination), if highly suspicious for malignancy. The core biopsy was performed by means of a 18-gauge needle in 89 lesions guided by palpation and in 190 lesions under ultrasound guidance. The results were compared with the final diagnosis: 19 benign lesions and 260 malignant lesions. RESULTS: In 63 lesions the results of the triple diagnostic approach were unequivocally malignant, this was confirmed in all cases. In 208 lesions the results of the needle core biopsy were malignant, without false positive results. However, there were 3 false negative results. The proportion of inconclusive needle core biopsies was higher when performed on palpation (35%) than when performed under ultrasound guidance (7%). When the specimen showed non-invasive carcinoma, a reliable prediction of invasion was not possible. In 264 cases excision of the lesion was performed. Given the unequivocally malignant triple diagnostic approach in 59 cases of the 264 patients operated (22%) frozen sections were not performed. By addition of needle core biopsy this percentage rose to 74%. CONCLUSION: Needle core biopsy is an important additional tool in the preoperative work-up of breast masses highly suspicious for malignancy, in order to reduce the number of frozen sections.

Biopsy, Needle↗