Biomedical subjects

J Hermans

Publications and source records attributed to J Hermans.

At least 181 records · Page 10Linked to original sources

PubMed1996

Molecular simulations of beta-sheet twisting.

Twisted conformations of two- and three-stranded antiparallel beta-sheet models containing alanine, glycine and valine with three or five residues per strand have been studied by molecular dynamics simulations. Free molecular dynamics and free energy simulations have been carried out to characterize the dynamics and energetics of the conformational change from a flat sheet to a twisted sheet. By altering the charges on the model in the free energy simulations, we have been able to analyze the contributions to the twist from electrostatic and van der Waals interactions. We have found that alanine and valine beta-sheets prefer conformations with a right-handed twist. In contrast, model glycine sheets do not have a pronounced preference to twist. Single beta-strands are found to be easily twisted, but to not have a strong preference for twisted conformations. Hence, the driving forces for the right-handed twist of beta-sheets must come principally from interactions between strands. These results disagree with several previous theoretical studies and constitute a different paradigm of the origin of beta-sheet twist observed in proteins.

Alanine↗

PubMed1996

Development and standardization of solid phase assays for the detection of anti-neutrophil cytoplasmic antibodies (ANCA). A report on the second phase of an international cooperative study on the standardization of ANCA assays.

Anti-neutrophil cytoplasmic antibodies (ANCA) are diagnostic markers for systemic vasculitis. They are classically detected by an indirect immunofluorescence test using normal donor neutrophils as substrate. This assay lacks antigenic specificity and is not quantitative. The 'EC/BCR Project for ANCA Assay Standardization' is an international collaboration study with the aim to develop and standardize solid phase assays for ANCA detection. In this part of the study the isolation and characterization of proteinase-3 and myeloperoxidase, the two main target molecules for ANCA, and the development and standardization of ELISAs with these antigens are described. Six laboratories successfully isolated purified proteinase-3 preparations that could be used. Three of these preparations, together with one myeloperoxidase preparation, were subsequently used for ANCA testing by ELISA. The ELISA technique was standardized in two rounds of testing in the 14 participating laboratories. The coefficient of variation of these new assays decreased from values of approx. 50% in the first round to approx. 20% in the second round. We conclude that purified proteinase-3 and myeloperoxidase can be used in standardized ELISAs for ANCA detection. Whether such procedures offer advantages over the IIF test will be determined in a prospective clinical study.

Antibodies, Antineutrophil Cytoplasmic↗

PubMed1996

[Multiple drug use by the elderly in need of care and nursing and possibility of reducing this practice].

OBJECTIVE: To determine and evaluate the simultaneous use of multiple drugs in elderly people (aged > or = 65 years). DESIGN: Cohort study. SETTING: Region Rijnstreek, the Netherlands. METHOD: In 200 consecutive persons who were evaluated for admission to a hospice or a nursing home, and who used > or = 5 drugs simultaneously, the drug use was determined and evaluated according to published guidelines and on the premise that the use of drugs ought to be reduced. RESULTS: A total number of 1131 persons (mean age: 80.4 years (SD: 6.4)) were evaluated in two study periods (January 1993-February 1994 and March-October 1994). The 200 selected patients (17.7%) used a mean of 6.9 drugs (SD: 1.9). Evaluation of these pharmacotherapeutic regimens, abolishing drugs deemed redundant, interaction screening and checks on dosage showed a number of opportunities for improvement although only a slight reduction in the number of drugs could be achieved (to 5.3 (SD: 1.9)). CONCLUSION: In practice, systematic re-evaluation of actual pharmacotherapeutic regimens on a regular basis is necessary. The increasing possibilities for self-medication should be taken into consideration.

Aged↗

PubMed1996

Interstitial rejection, vascular rejection, and diffuse thrombosis of renal allografts. Predisposing factors, histology, immunohistochemistry, and relation to outcome.

Histological and immunohistochemical analyses were made of biopsy specimens from 50 consecutive patients who experienced putative graft rejection. The mean age of the patients was 44.5 years (range, 17-69 years) and 26 were men. There were 67 evaluable allograft specimens, which were grouped according to the histological diagnosis: group 1, acute tubulointerstitial rejection (n = 42); group 2, acute vascular rejection (n = 18); and group 3, diffuse thrombosis (n = 7). Over a follow-up period of 21-57 months, the mean number of rejection episodes was 1.7, 2.8, and 3.3 in groups 1, 2, and 3, respectively. Allograft loss occurred in 7 out of 30, 10 out of 16, and 4 out of 4 patients in groups 1, 2, and 3, respectively. The following histological parameters differed significantly (P < 0.05) among the groups: interstitial edema, congestion of peritubular capillaries, glomerular thrombosis, and glomerular ischemia (group 3 > group 2 > group 1). Interstitial bleeding was seen more often in group 2 and 3 tissues than in group 1 specimens (P < 0.01). Immunohistochemical analyses showed that vascular rejection was associated with WT14 staining for monocytes and macrophages around the tubuli and with interstitial deposition of complement factor 3. With regard to serology, positive anti-endothelial cell antibody-dependent cellular cytotoxicity was associated with vascular rejection and thrombosis of the graft in all patients tested, and with graft loss in 75%. Pre-existent positive anti-IgG immunofluorescence on peritubular capillaries in pretransplant biopsy specimens incubated with patient serum was found in only 3 of the 50 patients, but was associated with graft loss in 2 of the 3. Cytomegalovirus infection was associated with a higher percentage of graft loss. There were significant intergroup differences in panel reactive antibodies before transplantation (P < 0.001), with higher titers in groups 2 and 3. The findings in relation to interstitial rejection are compatible with cellular rejection, while the data on vascular rejection support a humorally mediated pathogenesis.

Adolescent↗

PubMed1996

[Extensive lymph node dissection in stomach cancer? Initial results of the Dutch Stomach Cancer Study].

The five-year survival rate after curative resection for gastric cancer is higher in Japan (62%) than in the Netherlands (30%). In Japan, extensive D2 resection surgery is performed, in the Netherlands D(1) resection in which only the perigastric lymph nodes are removed. In a large prospective randomised trial, surgical departments of 80 Dutch hospitals compared the results of both resection types. A Japanese surgeon gave instruction in the D2 technique. D2 patients suffered more complications than D(1) patients and hospital mortality was 10% as against 4%. Demographic characteristics and concomitant morbidity might explain these differences. A change in current therapy is not advised at present. However, the surgical protocols and standards developed in connection with the trial reduced the overall death rate and morbidity of surgical treatment of gastric cancer in the Netherlands.

Adult↗

PubMed1996

Evaluation of various methods to quantify endothelial cells attached to vascular prostheses: comparison with a new "gold standard" FACS method.

For in vitro evaluation of functional properties of endothelial cells seeded on synthetic vascular prostheses accurate and reproducible quantification of cells is mandatory. Comparison of these properties with those resulting from other studies requires correlation of the functional parameters to reliably counted cell numbers. The accuracy of methods of quantification currently being used is unknown due to the lack of a "gold standard" method to which these methods can be compared. To determine the accuracy and reproducibility of four widely used methods, we have developed a "gold standard" model, using a flow cytometer (FACS). Endothelial cells, attached to collagen-coated Dacron vascular prostheses, were counted by four conventional methods and a new method of quantification after the attached number of cells had been determined with 99% accuracy by FACS. Subsequently, ratios were computed by dividing the cell numbers determined by the methods under investigation by those determined by FACS (x100%). The four conventional methods investigated were (1) removal and subsequent counting of cells from substrata by trypsin (T), (2) digestion of cells by citric acid and counting of crystal violet-stained cell nuclei (CV), (3) light microscopy after hematoxylin staining (LM), and (4) scanning electron microscopy (SEM). The new method consists of the measurement of cell fluorescence after labeling with fluorescein-diacetate (FDA). T and CV had average accuracy ratios of 127 +/- 58% and 96 +/- 48%, respectively (+/- standard deviation). The ratios for LM and SEM were 116 +/- 101% and 44 +/- 10% (respectively). FDA had a ratio of 99 +/- 7%. Reproducibility of cell quantification by T and CV was significantly less than that of quantification by LM, SEM, and FDA, as expressed by data on inter- and intraobserver agreement. Our results indicate that the investigated conventional methods of quantification failed to meet criteria of both high accuracy and reproducibility. Light microscopy and scanning microscopy methods were inaccurate but yielded reproducible countings. We conclude that the FACS method can serve as a "gold standard" to compare the accuracy and reproducibility of cell quantification methods. Moreover, the FDA method results in both accurate and reproducible quantification of endothelial cells attached to vascular prosthetic material.

Blood Vessel Prosthesis↗

PubMed1996

Randomised placebo-controlled study of stopping second-line drugs in rheumatoid arthritis.

BACKGROUND: A favourable benefit/risk ratio for treatment of rheumatoid arthritis (RA) with second-line drugs has been established only in short-term studies. The present investigation addresses the question of whether RA patients with a good response to long-term treatment with second-line drugs benefit from continuation of such treatment. METHODS: A 52-week randomised double-blind placebo-controlled multicentre study was conducted to assess the effect of stopping second-line therapy in 285 RA patients with a good long-term therapeutic response. The patients either continued the second-line drug (n = 142) or received a placebo (n = 143). The endpoint was a flare, defined as recurrence of synovitis. FINDINGS: At entry into the study median duration of second-line drug therapy was 5 years (range 2-33). At 52 weeks the cumulative incidence of a flare was 38% for the placebo group and 22% for the continued therapy group (p = 0.002). The risk of a flare was 2.0 times higher for patients receiving placebo than for those continuing the second-line drug (95% CI 1.27 to 3.17). The same trend was found for each second-line drug separately, with the exception of d-penicillamine. Side-effects that necessitated dose reduction or discontinuation occurred in 2 patients in each group. INTERPRETATION: Second-line drugs continue to be effective in RA patients who have responded well to initial treatment.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1996

Local irradiation alone for peripheral stage I lung cancer: could we omit the elective regional nodal irradiation?

PURPOSE: The results of local irradiation only for patients with Stage I lung cancer were analyzed to see whether the treatment of regional lymph nodes could be omitted. METHODS AND MATERIALS: One hundred and eight medically inoperable patients with nonsmall cell lung cancer (T1 and peripheral T2) were treated with 60 Gy split course or 65 Gy continuous treatment. The target volume included the primary tumor only, without regional lymph nodes. Response, survival, and patterns of failure were analyzed. RESULTS: The overall response rate was 85% with 50 (46%) complete responses (CRs). Overall survival at 3 and 5 years was 31 and 15%, and cancer-specific survival was 42 and 31% at 3 and 5 years, respectively. The actuarial 5 years local relapse free survival in patients with a CR was 52%. Tumor size (< or = 4 cm) was strongly correlated with the chance of complete remission and better survival. Of patients in complete remission, only two had a regional recurrence as the only site of relapse; an additional two patients had a locoregional recurrence. CONCLUSION: High-dose local radiotherapy on the primary tumor only is justified for medically inoperable patients with peripherally located nonsmall lung cancer. The low regional relapse rate does not support the need for the use of large fields encompassing regional lymph nodes. Using small target volumes, higher doses can be given and better local control rates can be expected.

Aged↗

PubMed1996

Serum neural cell adhesion molecule differentiates multiple myeloma from paraproteinemias due to other causes.

Serum neural cell adhesion molecule (NCAM) has been described as a prognostic marker in multiple myeloma (MM). Both C-reactive protein (CRP) and beta 2-microglobulin (beta 2M) are established prognostic markers in MM. We tested the diagnostic value of these markers in 212 serum samples of patients with paraproteinemia registered prospectively in a population-based registry. Sixty patients had MM and 152 had other monoclonal gammopathies (hematologic diseases [48], paraneoplastic disease [35], autoimmune disease [15], and monoclonal gammopathy of undetermined significance [56]). CRP and beta 2M had wide and overlapping ranges in all diagnostic categories. However, serum neural cell adhesion molecule (NCAM) was low (< 20 U/mL) in all but 4 of 152 nonmyeloma cases and high (> or = 20 U/mL) in 31 (52%) of the 60 MM cases. Two patients with non-Hodgkin's lymphoma, 1 with chronic lymphatic leukemia, and 1 with autoimmune disease had serum NCAM values between 20 and 30 U/mL. In a discriminant analysis in which serum NCAM, CRP, beta 2M, paraprotein type and concentration, hemoglobin, leukocyte and thrombocyte counts, creatinine, corrected calcium, lactate dehydrogenase, and alkaline phosphatase were included, paraprotein type and concentration and serum NCAM turned out to be the best combination of parameters predicting whether a patient had MM, with 89% of cases being correctly classified. Even without bone marrow and x-ray examinations, serum NCAM, in combination with paraprotein type and concentration, can differentiate between MM and nonmyeloma patients.

Adult↗

PubMed1996

Hydrophilicity of cavities in proteins.

Water molecules inside cavities in proteins constitute integral parts of the structure. We have sought a quantitative measure of the hydrophilicity of the cavities by calculating energies and free energies of introducing a water molecule into these cavities. A threshold value of the water-protein interaction energy at -12 kcal/mol was found to be able to distinguish hydrated from empty cavities. It follows that buried waters have entropy comparable to that of liquid water or ice. A simple consistent picture of the energetics of the buried waters provided by this study enabled us to address the reliability of buried waters assigned in experiments.

Hydrogen Bonding↗

PubMed1996

Energetic decomposition of the alpha-helix-coil equilibrium of a dynamic model system.

Using molecular dynamics simulations to calculate free energies of molecular transformation, we have computed helix-coil transition free energies for alanine oligomers up to 14 residues long. The simulations have been done on the model in vacuo with dielectric constant, epsilon = 1, 5, 25, and infinity and on the model in solution with explicit representation of water molecules and with partial charges on the oligomer set to zero. (The analogous simulations of the solvated model with full charges on the oligomer were reported elsewhere [L. Wang et al. (1995) Proceedings of the National Academy of Science USA 92, 10924-10928]). In vacuo, both entropic and electrostatic contributions oppose formation of a 3-residue helical nucleus in the helix initiation step. The entropy change opposing helix growth is found to be 3 e.u., van der Waals interactions favor helix growth by 1.9 kcal/mol, and electrostatic interactions favor helix growth by 3 kcal/mol (for epsilon = 1; all these values are per residue). In water, helix stability is slightly greater for the zero-charge model than for the full-charge model, i.e., the polypeptide's electrostatic interactions, which include hydrogen bonds, slightly destabilize the helix. The helix stabilizing contribution of the hydrophobic effect was found to be identical to that of the van der Waals interactions in vacuo (i.e., 1.9 kcal/mol per residue). The zero-charge model has nearly identical helix stability in vacuo and in water, the almost identical free energies of transfer of helix and coil state of the zero-charge oligomer from vacuum to water are found to be small. Thus, the results of this systematic variation of the force field afford a meaningful decomposition of the free energies for helix initiation and growth.

Entropy↗

PubMed1996

Prognostic value of positive cytology findings from abdominal washings in patients with gastric cancer.

The poor prognosis of patients with gastric cancer with free abdominal tumour cells on cytological examination has been described in Japan. In a randomized trial in the Netherlands comparing D1 and D2 lymphadenectomy for gastric cancer, patients were subjected to cytological examination of abdominal washings on an optional basis; findings were of no consequence for scheduled treatment. Cytology results in 535 patients were obtained, in 457 (85.4 per cent) after curative resection and in 78 (14.6 per cent) after palliative operation. There was a clear association of positive cytology results with serosal invasion (12 per cent positive cytology) and lymph node infiltration (7.5 per cent positive cytology). Survival of those with positive cytology results was significantly lower than that of those with negative findings, irrespective of the procedure employed (curative or palliative). Cytological examination of abdominal washings increases the accuracy of staging and improves the selection of patients suitable for curative or palliative resection.

Aged↗

PubMed1996

DNA index reflects the biological behavior of ovarian carcinoma stage I-IIa.

The prognostic significance of histologic grade, morphometric analysis, and DNA flow cytometry was evaluated in 64 patients with well-differentiated (group A) and 30 patients with moderately and poorly differentiated (group B) early-stage (FIGO stages Ia, Ib, Ic, and IIa) epithelial ovarian cancer. The extent of the well-defined staging procedure was assessed strictly in every patient. Of 94 patients, 13 had recurrent ovarian cancer (5 from group A and 8 from group B) and 12 of these patients died. A significant difference was found between groups A and B for 5-year disease-free survival (91% versus 75%), the menopausal status, surgical staging procedure, volume percentage epithelium (VPE), morphometric category, DNA ploidy, and DNA index, but not for histologic cell type. For the 94 patients from groups A and B together, a significant difference was observed between diploid and aneuploid tumors with regard to mean mitotic activity index (MAI), mean VPE, and the morphometric categories that combined MAI and VPE characteristics. Prognostic reliability for the occurrence of tumor relapse was highest for DNA index class, followed by tumor grade and DNA ploidy pattern. With multivariate analysis the primary prognostic factor for disease-free survival appeared to be the DNA index. DNA index class was the only parameter that added prognostic information when histologic grade was selected as the primary prognostic factor. If the DNA index was taken as primary prognostic factor, none of the tested parameters including tumor grade added useful information. It was concluded that the DNA index is a primary prognostic factor for disease-free survival in early-stage ovarian cancer patients. Morphometric measurements do not add supplementary prognostic information.

Adult↗

PubMed1996

Techniques for genetic engineering in mycobacteria. Alternative host strains, DNA-transfer systems and vectors.

The study of mycobacterial genetics has experienced quick technical developments in the past ten years, despite a relatively slow start, caused by difficulties in accessing these recalcitrant species. The study of mycobacterial pathogenesis is important in the development of new ways of treating tuberculosis and leprosy, now that the emergence of antibiotic-resistant strains has reduced the effectiveness of current therapies. The tuberculosis vaccine strain M. bovis BCG might be used as a vector for multivalent vaccination. Also, non-pathogenic mycobacterial strains have many possible biotechnological applications. After giving a historical overview of methods and techniques, we will discuss recent developments in the search for alternative host strains and DNA transfer systems. Special attention will be given to the development of vectors and techniques for stabilizing foreign DNA in mycobacteria.

Cloning, Molecular↗

PubMed1996

Relationship between atlanto-odontoid osteoarthritis and idiopathic suboccipital neck pain.

We discuss the relationship of atlanto-odontoid (AO) (anterior C1-C2 joint) osteoarthritis to suboccipital pain. A questionnaire regarding suboccipital neck pain was presented to 210 consecutive patients undergoing computed tomography (CT) of the brain or sinuses for a variety of indications. In all patients the AO joint and the lateral scout image of the cervical spine were studied. In 104 (49%) degenerative changes were seen at the AO joint. There were 89 patients (42%) who reported pain in the suboccipital region, although this was not the reason for CT in any patient. Statistical analysis of the prevalence of suboccipital neck pain in all patients showed the presence of AO osteoarthritis seen on CT to be associated with occurrence of these symptoms. This association remained significant in the same study population after excluding patients with a history of rheumatoid arthritis, migraine, stress and neck trauma and patients with signs of degenerative changes of C2-C7 on the computed lateral scout image.

Adolescent↗

PubMed1996

Health-related quality of life assessments in osteoarthritis during NSAID treatment.

There is some evidence that nabumetone (1000 mg once daily) in comparison with piroxicam (20 mg once daily) in patients with OA in general practice is associated with a lower incidence and less severe occurrence of stomach pain but with more withdrawals due to lack of efficacy. The aim of this analysis was to investigate whether these differences are reflected in health-related quality of life assessments. Patients (n = 198) included in this study were selected in general practice according to a protocol. The patients were randomized and treated for a period of six weeks. Clinical assessments were performed by the general practitioner (CP) during treatment. The Sickness Impact Profile (SIP), the Activities of Daily Living (ADL), and a pain questionnaire were filled out by the patients before and after treatment. As measured with the SIP, the ADL and the pain questionnaire, there were no significant differences between nabumetone and piroxicam. The correlations between (changes in) patient assessments and (changes in) clinical assessments were low. The differences between the two drugs regarding withdrawals and adverse events were not reflected by patient health-related quality of life assessments. There was a low correlation between patient health-related quality of life assessment and clinical assessments. To get a complete picture of the efficacy and safety of a drug, patient health-related quality of life assessments should be a part of a clinical trial.

Adult↗

PubMed1996

Early recognition of Streptococcus pneumoniae in patients with community-acquired pneumonia.

The objective of this study was to assess the predictive value of signs, symptoms, and rapidly available laboratory parameters for pneumococci in community-acquired pneumonia (CAP). A prospective study on patients with CAP who were admitted to hospital was conducted. Clinical and laboratory data were collected according to a protocol. Two hundred sixty-eight patients aged 18 years or older, not living in a nursing home or not admitted to hospital within one week of this admission, with a new infiltrate on the chest radiograph consistent with pneumonia were included. According to microbiological and serological tests, patients were allocated to one of two aetiological groups, Streptococcus pneumoniae or "other pathogens". Seventy-three variables were examined for a correlation with one of the aetiological categories by means of univariate and multivariate analysis. The resulting discriminant function was considered a clinical test for which posttest probabilities for pneumococcal pneumonia were calculated. Streptococcus pneumoniae was demonstrated in 79 patients and other pathogens in 83; no pathogens were detectable in 106 patients. The variables "cardiovascular disease", "acute onset", "pleuritic pain", "gram-positive bacteria in the sputum Gram stain", and "leucocyte count" correctly predicted the cause of CAP in 80% of all cases in both groups. Depending on the prevalence of Streptococcus pneumoniae, posttest probabilities for pneumococcal pneumonia were up to 90%. It is concluded that data on history, together with the result of the Gram stain of sputum and the leucocyte count, can help to distinguish Streptococcus pneumoniae from other pathogens causing CAP.

Acute Disease↗

PubMed1996

Can conventional radiographs be used to monitor the effect of neoadjuvant chemotherapy in patients with osteogenic sarcoma?

OBJECTIVE: The objective of this study was to assess the effectiveness of conventional radiography in predicting histopathologic response in patients with osteogenic sarcoma who were treated with preoperative chemotherapy. DESIGN AND PATIENTS: The radiographs of 22 patients with an osteogenic sarcoma, taken before and after neoadjuvant chemotherapy, were reviewed. Tumour location, size, radiographic appearance, margination, cortical destruction and periosteal reaction were evaluated. The findings were correlated with the histopathologic response of the surgical specimen. RESULTS: None of the findings proved to be of predictive value for the histopathologic response. Increase in tumour diameter and increase in ossification and/or calcification, which were seen in more than half of the patients, did not correlate with response. CONCLUSION: Conventional radiographs do not contribute to the identification of good or poor responders.

Adolescent↗