PubMed HealthSearch

Biomedical subjects

J Hermans

Publications and source records attributed to J Hermans.

At least 19 recordsLinked to original sources

Hereditary protein C-deficiency: laboratory values in transmitters and guidelines for the diagnostic procedure. Report on a study of the SSC Subcommittee on Protein C and Protein S. Protein C Transmitter Study Group.

A multicenter study on protein C-antigen and -activity values was carried out in transmitter patients with hereditary protein C deficiency (diagnosis established by pedigree analysis) and in normal controls in order to (1) establish the range of protein C levels in genetically determined heterozygotes and (2) to evaluate the usefulness of statistical procedures to discriminate between protein C deficient patients and controls. In transmitters absolute protein C activity values ranged from 19 to 82% and antigen values from 22 to 88.5%. Most transmitter patients could clearly be differentiated from the control group. However, in some transmitter patients values of protein C were within the range of the control group. The discrimination between transmitters and controls could be improved by statistical procedures. Using tolerance ellipses the overlapping area of the two groups was smallest when (factor II antigen+factor X antigen)/2 was plotted against protein C antigen. To specify the degree of uncertainty likelihood ratios were calculated to obtain the posterior probability for an individual for being deficient or not. In quadratic discriminant analysis the best discrimination between transmitters and controls was obtained using protein C activity versus factor X antigen and protein C antigen versus factor X antigen. Based on these analysis an equation was derived, which allows the calculation of the likelihood ratio favouring deficiency or non-deficiency in an individual.

Antigens

Effect of preservation solution on results of cadaveric kidney transplantation. The European Multicentre Study Group.

University of Wisconsin (UW) preservation solution has been reported to be beneficial for canine organ transplants and for human liver and pancreas transplants. To examine whether it affects renal graft survival, a randomised multicentre trial was conducted to compare its effect with that of EuroCollins solution on delayed graft function, renal function, and patient and graft survival in 695 recipients of cadaveric renal transplants. 352 kidneys were preserved with UW and 343 with EuroCollins solution. Delayed graft function occurred in 23% of the UW group and in 33% of the EuroCollins group (p = 0.003). Three factors other than type of preservation fluid were associated with a higher incidence of delayed graft function: older donor age, intracerebral haemorrhage in the donor, and oliguria in the donor. Renal function as indicated by serum creatinine concentration was better in the UW than in the EuroCollins group. Patient survival in the UW and EuroCollins groups after 1 year was 95% and 94%, respectively. In both groups, delayed graft function reduced 1-year graft survival by 15% (p = 0.0001). 1-year graft survival of UW-preserved kidneys was 6% higher than that of controls (88.2% vs 82.5%, p = 0.04). Delayed graft function is significantly associated with a reduction in 1-year graft survival. The preservation solution is the most important factor influencing development of delayed graft function, and UW solution is superior to EuroCollins solution in reducing occurrence of delayed graft function, improving graft function, extending graft survival.

Adolescent

Differential helix propensity of small apolar side chains studied by molecular dynamics simulations.

A series of oligoalanine molecules with single amino acid replacements in the middle of the chain has been studied by molecular dynamics simulations. Differences in stability of the alpha-helix (as free energies delta delta G degrees) were estimated for the following series of residues: alpha-aminoisobutyric acid, alanine, alpha-amino-n-butyric acid, valine, glycine, D-alanine, t-leucine (= alpha-amino-beta,beta-dimethyl-n- butyric acid), and proline, arranged here in decreasing order of helix-forming potential. (The results for proline and valine had been reported earlier.) No experimental results were available for alpha-amino-n-butyric acid, D-alanine, and t-leucine at the time these calculations were done. The values of delta delta G degrees, including the three predictions, are in striking agreement with recent experimental results. A combination of free dynamics, dynamics with forced conformational change, and dynamics with forced molecular replacement was used. Conformational distributions were calculated for the peptide backbone of the dipeptides and, where appropriate, for the side chains of the dipeptide and the alpha-helix. The results demonstrate an unexpected level of accuracy for the all-atom model used to represent atomic interactions in the simulations. The simulations permit a detailed analysis of different factors responsible for conformational preferences and differences in stability. These conclusions drawn from this analysis agree with accepted qualitative explanations and allow these explanations to be quantitated to an extent not heretofore possible.

Alanine

[Non-urgent patients in a non-traumatology Emergency Service; general aspects and screening for psychiatric disorders].

The Emergency Department is used by a rather large number of patients with a non-urgent condition. It is unknown whether the request for medical assistance for non-urgent conditions is partly due to the presence of a mental disorder. We conducted a cross-sectional study of 711 patients of a non-traumatic Emergency Department. The prevalence and determinants of non-urgent conditions and of mental disorders of non-urgent patients were studied. Of all patients, 31% had a non-urgent condition. Self-referrals and young adults more often had a non-urgent condition. However, in our study only 17% of all patients were self-referred. The prevalence of a score greater than or equal to 5 on the general health questionnaire (GHQ), an indication of the presence of a mental disorder, in the non-urgent patients was 59%. Non-acute symptoms, life events, the use of psychotropic drugs and alcoholism were determinants for a high GHQ score, but their specificity was low. It is advised to include questions concerning mental disorders in the medical interview of non-urgent patients.

Academic Medical Centers

The value of aspiration cytologic examination of the breast. A statistical review of the medical literature.

The decision to perform surgery in patients with a breast mass usually is made on the basis of combined diagnostic information, with fine-needle aspiration cytologic examination (FNAC) playing a central role. To determine and compare the quality of FNAC of the breast, a search was performed of the English literature for articles with quantitative information about their results. Twenty-nine such articles, containing 31,340 aspirations, were identified and summarized. Required data were extracted from these articles. These numbers were analyzed with the use of a two-by-four contingency table to relate the FNAC result (definitely malignant, suspect, benign, or unsatisfactory cytologic material) with the final diagnosis (malignant or benign breast disease). Test characteristics such as sensitivity, specificity, and the likelihood ratios for the four different FNAC results were derived for each study and compared. There was a striking difference between studies with regard to the probability of a particular FNAC upshot (e.g., in patients with breast cancer, the chance of obtaining definitely malignant cytologic material ranged from 0.35 to 0.92), the sensitivity (range, 0.65 to 0.98), the specificity (range, 0.34 to 1.0), and likelihood ratios. In the opinion of the authors, it is virtually impossible to infer general test characteristics of FNAC of the breast from the medical literature because of differences in methods and different biases. At best, the maximum attainable performance of this test can be described. For the development of a policy for breast mass management, the local test characteristics of this highly operator-dependent test should be established.

Biopsy, Needle

Fractional allelic imbalance in human breast cancer increases with tetraploidization and chromosome loss.

We have previously reported a complete allelotype study of 86 primary breast carcinomas, in which each non-acrocentric chromosome arm was studied with at least one polymorphic DNA-marker for the presence of allelic imbalance (AI, allelic loss or allelic gain) in the tumor. Here we report the statistical analysis of this data set, investigating the relationships between AI, DNA aneuploidy and several clinico-pathological parameters of tumor progression. AI on 13 different chromosome arms, including 3p, 11p, and 17p, correlated significantly with the total number of AI events at other sites, suggesting that they are progression-related events. AI at 1q and 16q did not show such a correlation and may thus represent earlier events. Mean fractional allelic imbalance (FAI) was significantly higher in flow cytometrically aneuploid tumors than in diploid tumors (0.27 vs. 0.17, p = 0.007), and was highest in hypotetraploid tumors (0.37). This suggests that tetraploidization followed by chromosome segregation may underlie the development of AI at multiple sites. No correlation was found between mean FAI and clinico-pathological variables such as lymph-node involvement, stage, age, estrogen-receptor content and development of distant metastases, although there was a noticeable trend towards impaired survival for those patients with a higher-than-median FAI value.

Alleles

A randomized clinical trial comparing two methods of fascia closure following midline laparotomy.

Three hundred forty women undergoing midline laparotomy were randomized into an interrupted suture (polyglactin 910, size 1) or a continuous suture (polyglyconate, size 0) closure group. The two groups were well balanced with respect to various risk factors for postoperative wound complications. Early evaluation revealed no differences between the continuous and interrupted suture groups with respect to wound infection (3% vs 1%), superficial wound dehiscence (2% vs 4%), and deep wound dehiscence (0.6% vs 0%). Late evaluation showed no differences between the two groups either. Continuous polyglyconate and interrupted polyglactin 910 sutures had a similar incidence of suture fistula (0% vs 2%), wound pain (1% vs 2%), and incisional hernia (3% vs 4%). Continuous closure was done faster and resulted in less foreign-body suture material. Despite its smaller diameter, the polyglyconate suture also retains a higher tensile strength after surgery than does the quicker-degrading polyglactin 910 suture. Results of this study lead to the conclusion that a running polyglyconate suture is the better choice for closure of the abdominal-wall fascia following midline laparotomy.

Abdominal Muscles

Homologous genes for the C4 isoform of phosphoenolpyruvate carboxylase in a C3 and a C4 Flaveria species.

The C4 isoform of phosphoenolpyruvate carboxylase (PEPCase) in Flaveria trinervia is encoded by the ppcA subgroup of the PEPCase gene family and is abundantly expressed in the mesophyll cells of leaves. The homologous ppcA genes in the C3 plant F pringlei are only weakly expressed and their transcripts do not show the strictly leaf-specific accumulation pattern observed for the F. trinervia genes. Two representative members of the ppcA subfamilies of F. trinervia (C4) and F. pringeli (C3)-named ppcA1-were characterized by Southern blotting, nucleotide sequencing and primer extension analysis. Comparison of the deduced amino acid sequences reveals a close similarity between C4 and C3 isoforms. Only few C4-specific positions can be detected when all known plant PEPCases are included in the comparison. A regulatory domain involved in light-dependent phosphorylation/dephosphorylation of the C4 and crassulacean acid metabolism (CAM) isoforms is present in the ppcA1 gene products of both the C3 and C4 Flaveria. The 5' flanking regions are essentially homologous. The putative promoter regions share several identical sequence motifs (CCAAT, AT-1 and GT-1 box III/III* elements). Additionally, alterations in elements that could contribute to differences in expression rates and light regulation are found. The significance of these findings is discussed with respect to the molecular evolution of C4 photosynthesis in Flaveria.

Amino Acid Sequence

Defecography and anorectal manometry.

In a prospective study anorectal manometry was performed in 160 consecutive patients who were referred for defecography. Leakage of contrast material of standardized viscosity, the anorectal angle (ARA), anal resting pressure (Pr) and squeeze pressure (Ps) were measured and analyzed. This was done to investigate the role of ARA on rectal continence during defecography and to investigate whether relevant findings of manometry can be predicted from findings at defecography as part of the diagnostic work-up in selected patients in order to avoid manometry in these patients. The ARA was of significance in maintaining rectal continence for the contrast medium (P = 0.008). With increasing leakage, Pr and Ps decreased significantly (P less than 0.001). In all fully incontinent patients (n = 36) Ps was distinctly below normal values. Manometry can be avoided in these patients if the level of Pr is not important for therapeutic strategy.

Adult

Significance of local recurrence after mastectomy for breast cancer.

In a retrospective study 678 patients who underwent (modified) radical mastectomy between 1970 and 1986 were analysed. By comparing the groups of patients who experienced local recurrence, regional recurrence or distant metastasis during follow-up with patients who remained free of disease, we have tried to gain some insight into the significance of local recurrence. By looking at the prognostic factors and the disease-free period there is hardly any difference between the patients with either a local, regional or distant recurrence. Actuarial survival of patients with local recurrence is slightly better than the survival of patients with distant metastasis (P = 0.009). From our results and from the literature we conclude that an isolated local recurrence after mastectomy for breast cancer is, in most cases, a first manifestation of metastatic disease. Probably only a minority of the local recurrences is caused by tumour cells left behind in the operation field.

Adult

The prognostic value of hemoglobin and a decrease in hemoglobin during radiotherapy in laryngeal carcinoma.

An association between a low Hb-content and a poor response on radiation therapy has been established in previous years, especially in patients with squamous cell carcinomas. Whether this is linked with hypoxic conditions of the tumour or associated with tumour volume, blood loss or other conditions, is not yet known for certain. Patients with small head and neck tumours seem to form an interesting group to study this issue because several factors can be ruled out. Therefore, a retrospective analysis of 306 patients with glottic or supraglottic carcinoma was performed, to identify whether the Hb-value was of prognostic importance and whether this was linked to other patient characteristics. All patients were treated with primary radiotherapy with doses ranging from 60 to 70 Gy in 6-7 weeks. It appeared that in glottic carcinoma, the disease-free survival was significantly worse in patients with a Hb-value below normal at the start or/and at the end of therapy (p = 0.09, p = 0.0012, respectively). In patients with supraglottic carcinoma, the above mentioned difference approved only for a Hb-value below normal at the end of treatment (p = 0.05). A decrease in Hb-level of greater than or equal to 0.5 mmol/l during therapy, regardless whether the Hb-values were within or beyond normal range, reduced the disease-free survival in patients with glottic carcinoma (p = 0.0125). In a multivariate analysis, the Hb-value at the end of treatment proved to be an independent prognostic factor after T- and N-classification. There was no relationship with nutritional condition of the patient, nor with the Karnofsky Performance scale.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Squamous Cell

Cytokine-induced immunoglobulin production in primary IgA nephropathy.

Increased IgA synthesis probably plays a role in the pathogenesis of IgA nephropathy (IgAN). We investigated whether an increased sensitivity to the effect of various growth factor combinations leads to increased immunoglobulin synthesis by peripheral blood mononuclear cells (PBMC) from IgAN patients, in comparison to healthy controls. Although none of the growth factors studied (pokeweed mitogen [PWM], interleukin [IL]-2, IL-6, transforming growth factor-beta [TGF-beta], and combinations) led to greater IgA synthesis in IgAN patients than in controls, the IgA subclass ratio was shifted in favor of IgA1. In controls, but not in IgAN patients, IL-2 enhanced the production of IgA and IgA1 compared with media alone. This possibly reflects previous in vivo activation by IL-2 in IgAN patients. The suppressive effect of TGF-beta on immunoglobulin synthesis was modestly greater in IgAN patients than in controls. Increased production of IL-2 and perhaps other cytokines by T cells in vivo may be responsible for the elevated IgA immune response in these patients.

Adolescent

Application of free energy simulations to the binding of a transition-state-analogue inhibitor to HIV protease.

Free energy simulations (slow-change method) have been used to estimate quantitatively the ratio of the binding constants of (S) and (R) isomers of a novel HIV protease inhibitor, JG365. As a starting geometry, we used the X-ray crystallographic structure of a complex of HIV protease and JG365 provided by A. Wlodawer. According to our results the (S) configuration, i.e. the form previously identified experimentally, binds considerably more tightly to the protease (delta delta G degrees = 2.9 kcal/mol). When the (S) inhibitor is bound, there is a very strong preference for protonation of the Asp125 (rather than the Asp25) residue of the protease. This study is the first to apply a new method for quantitatively assessing the precision of free energies calculated by the slow-change method.

Binding Sites

Magnetic resonance evaluation of regional left ventricular function. Effect of through-plane motion.

RATIONALE AND OBJECTIVES: Measurements of segmental contraction of the left ventricle by standard magnetic resonance imaging (MRI) and two-dimensional echocardiography involve the comparison of diastolic and systolic time frames acquired from the same imaging plane in space. As the cone-shaped left ventricle shortens along its long axis during systole, the observed contraction may differ from the true myocardial contraction. METHODS: Spin-echo MRI examinations in 21 healthy subjects were performed to evaluate the error caused by failing to compensate for through-plane motion. RESULTS: The authors found that at the base and the mid-ventricle the observed contraction systematically underestimates true contraction by an average of 16% and 21%, respectively (P less than .001). At the apex, the segmental contraction may be overestimated or underestimated. CONCLUSIONS: Because of this error, standard MRI and echocardiography are less suited for basic research on cardiac contraction patterns. However, standard imaging techniques are valuable in clinical studies comparing groups of patients, because all measurements will suffer from the same systematic error.

Adult

Kidney depth measured by using 99Tcm-DMSA. Comparison with CAT scan: review of 50 measurements.

Measurement of kidney depths using computed axial tomographic (CAT) scans, considered as the gold standard, has been compared in 25 patients with depth measured using an isotopic method (99Tcm-DMSA). 99Tcm-DMSA underestimates renal depth in 78% of the cases (mean underestimation: 0.78 cm). The correlation coefficient between the two methods is 0.82. As a comparison, kidney depths calculated using Tonnesen's formula are also given and related to CAT scan results. The presence of renal morphological abnormalities in 18% of the studied kidneys allowed the authors to study their potential influence on 99TcmDMSA measurements. They do not seem to be very different from those obtained in morphologically normal kidneys. The different methods for kidney depth measurement described in the literature are briefly reviewed.

Adult

A randomized clinical trial on the benefit of adhesiolysis in patients with intraperitoneal adhesions and chronic pelvic pain.

OBJECTIVE: To see whether surgical adhesiolysis would improve pelvic pain in women with pelvic adhesions. DESIGN: Randomized clinical trial comparing surgery (adhesiolysis) with no surgery with final analysis of results after 9-12 months. SETTING: Department of Gynecology, Leiden University Medical Center, the Netherlands. SUBJECTS: 48 women known by laparoscopy to have stage II-IV pelvic adhesions. INTERVENTIONS: Midline laparotomy and surgical adhesiolysis. MAIN OUTCOME RESULTS: Pelvic pain assessed by the McGill pain score, subjective pain assessment and disturbance of daily activities. RESULTS: 24 women were randomly allocated to undergo surgical adhesiolysis and 24 to a control group who did not have surgery. After 9-12 months there were no significant differences between the two groups overall with regard to pelvic pain. A subgroup of women with severe, vascularized and dense adhesions involving bowel (stage IV) had significantly less pelvic pain after adhesiolysis for two of the three methods of assessment. CONCLUSIONS: Adhesiolysis for the treatment of pelvic pain is not indicated in women with light or moderate degree pelvic adhesions. It may be beneficial in those with severe adhesions involving the intestinal tract.

Adult

Osteosarcoma: chemotherapy-induced changes at MR imaging.

Fifty-seven patients undergoing chemotherapy for osteosarcoma underwent evaluation with magnetic resonance (MR) imaging to identify changes related to a good or poor response. Spin-echo MR images obtained after preoperative chemotherapy were compared with images obtained before treatment. Histopathologic examination of each resected specimen was used to quantify the response. An increase in tumor volume and increased or unchanged edema were predictive of a poor histopathologic response (predictive values, 85%-92%). Decreased or unchanged tumor volume and a decrease in edema were poor predictors of a good response (predictive values, 56%-62%). Improved tumor demarcation, an increase in the size of areas of low signal intensity, and a decrease in joint effusion occurred independently of histopathologic response in almost half of the patients. With a subjective interpretation of MR images, poor respondents can be identified if an increase in tumor volume or no decrease in the amount of edema is seen. Subjective criteria do not contribute to the identification of good respondents.

Adolescent

Long-term effects of chemotherapy in patients with testicular cancer.

PURPOSE: Combination chemotherapy regimens that include cisplatin (CDDP) and bleomycin (BLE) result in the cure of the majority of patients with malignant germ cell tumors of the testis. We investigated the long-term damage of such chemotherapy to renal, pulmonary, and hearing function. PATIENTS AND METHODS: Forty-three patients with disseminated testicular carcinoma were studied 1.5 to 9.3 years (median, 4.1 years) after completion of chemotherapy. All 43 patients received CDDP; of these, 39 also received BLE, 27 vinblastine (VLB), and 27 etoposide (VP-16). Mean cumulative doses of individual cytotoxic drugs administered were CDDP 483 mg/m2 (range, 189 to 1,173 mg/m2), BLE 160 mg/m2 (range, 81 to 311 mg/m2), VLB 31 mg/m2 (range, 19 to 158 mg/m2), and VP-16 667 mg/m2 (range, 242 to 1,455 mg/m2). RESULTS: In the majority of cases, values of renal, pulmonary, and hearing function were within the normal range before treatment. An initial decrease in renal, pulmonary, and hearing function was observed, with recovery of pulmonary function at late follow-up. On average, a decrease of 15% in creatinine clearance rates was observed at late follow-up. Long-term effect on audiometric function was considerable, but frequencies affected were outside the range of conversational speech. With multivariate analysis, no overall relation between the cumulative doses of the individual drugs and the loss in organ function was found; the cumulative doses of CDDP and BLE only contributed approximately 30% to the loss in renal function and vital capacity, respectively. CONCLUSION: Chemotherapy-induced pulmonary toxicity is reversible, whereas nephrotoxicity and ototoxicity are not. However, the long-term effects of chemotherapy in testicular cancer patients were minor and not invalidating.

Adult