Biomedical subjects

J Hermans

Publications and source records attributed to J Hermans.

At least 343 records · Page 19Linked to original sources

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

The objective response of brain metastases on radiotherapy. A prospective study using computer tomography.

A prospective study was performed to establish the objective response of brain metastases after radiotherapy. Twenty-five patients with a total of 53 metastatic lesions were evaluated approximately 6 weeks after completing the treatment (30 Gy/2,5 weeks). Clinical response was seen more often than objective response, due probably to concomitant use of corticosteroids and to most patients having multiple metastases. Clinical response, although important for the patient, does not well reflect the objective response. In 48% of the cases there was agreement between the clinical and the radiodiagnostic findings. The tumor size was an important prognostic factor for prediction of complete response. The majority of patients who achieved complete remission of at least one of the metastatic lesions, did not show recurrence of the neurological symptoms.

Actuarial Analysis↗

PubMed1992

R2 compared with R1 resection for gastric cancer: morbidity and mortality in a prospective, randomised trial.

OBJECTIVE: To compare the postoperative course of patients in the Dutch nationwide randomised trial of R1 (conventional) compared with R2 resection (including extended lymph node dissection) in the treatment of gastric cancer. DESIGN: Prospective randomised controlled trial. SETTING: National multicentre trial with 72 participating hospitals in The Netherlands. SUBJECTS: 192 patients who were operated on between August 1989 and May 1990. INTERVENTIONS: 96 patients were randomised for a R1, and 96 for a R2 resection. MAIN OUTCOME MEASURES: Morbidity and mortality among 131 patients (64 R1 and 67 R2) for whom the resection was performed with curative intent. RESULTS: The groups were comparable for age, sex, type of resection, site of tumour and depth of invasion. Complications developed in 23 R1 (36%) and in 29 R2 patients (43%). Seven patients died in the postoperative period. Median hospital stay was significantly longer after R2 (18 days, range 7-122) than after R1 resection (15 days, range 2-63) (p < 0.05). Morbidity and mortality among the patients whose R2 resection was done by the Japanese instructor (n = 34) did not differ significantly from those among patients operated on by the Dutch supervisors (n = 33), but those operated on by the Japanese instructor stayed in hospital significantly longer (20 compared with 16 days, p < 0.05). CONCLUSIONS: If R2 resections are carried out by properly trained surgeons under supervision, they can be done safely. The reported high morbidity after R2 resection in Western countries seems to result from a lack of proper instruction and quality control.

Adenocarcinoma↗

PubMed1992

The effects of aortic reconstruction and collagen impregnation of Dacron prostheses on the complement system.

Complement activation has been associated with numerous clinical hazards such as platelet aggregation, adult respiratory distress syndrome, and renal dysfunction. The complement system is activated by exposure of different biomaterials to blood. Recently a watertight knitted Dacron aortic prosthesis impregnated with bovine collagen has been developed. One potential disadvantage is that this bovine collagen may activate the complement system and evoke the production of inflammatory mediators. We conducted a prospective randomized trial to study the systemic effects of collagen-impregnated prostheses and of aortic surgery with implantation of Dacron prosthesis on the complement system in the perioperative period and at 3 months after operation. Forty-one patients randomly received either a collagen-impregnated (n = 20) or a nonimpregnated prosthesis (n = 21). Twelve patients who had cholecystectomy served as controls. CH50 consumption and C3a generation were determined to study overall complement activation. Furthermore, C3a/C3 fractions were calculated. Finally, C4 and factor B consumption were determined to evaluate the complement stimulation via the classic and the alternative pathways, respectively. We found significant activation of the complement system during the operation in both the collagen group (CH50 consumption: 40%, p = 0.03; C4 consumption: 74%, p < 0.0001; factor B consumption: 73%, p < 0.0001; C3a/C3 fraction increase: 173%,p = 0.04), and the nonimpregnated group (CH50 consumption: 40%, p < 0.0001; C4 consumption: 71%, p < 0.0001; factor B consumption: 76%, p < 0.0001; C3a/C3 fraction increase: 165%, p = 0.025), with no statistically significant differences between the groups of prostheses. Activation was initiated via both the classic and the alternative pathway. This indicates aortic implantation significantly activates the complement system, but that collagen-impregnated prostheses do not stimulate the complement system any more than its nonsealed substrate. Comparing results in patients with vascular disease with controls, a significantly increased complement activation was observed in the vascular group (CH50 consumption: 40%, p < 0.0001; C4 consumption: 74%, p < 0.0001; factor B consumption: 75%, p < 0.0001; C3a/C3 fraction: 169%, p = 0.002), compared with the controls (CH50 consumption: 71%; C4 consumption: 104%; factor B consumption: 94%; C3a/C3 fraction: 119%, all p = NS), with statistical significant differences between the vascular group and cholecystectomies (CH50: p = 0.005; C4: p = 0.002; factor B: p < 0.0001, and C3a/C3 fraction: NS). This observation demonstrates that aortic surgery with the implantation of a Dacron prosthesis significantly activates the complement system.

Adult↗

PubMed1992

Protective effect of pulmonary surfactant on elastase-induced emphysema in mice.

The aim of this study was to obtain some evidence of a protective role for pulmonary surfactant in the pathogenesis of emphysema. Firstly, we developed a quick and easy method to treat mice with a series of intratracheal instillations. Subsequently, three groups of mice were treated as follows: two groups received intratracheal instillations with pancreatic elastase (1.8 mg.kg-1 BW) followed after 3, 48 and 96 h in one group (El/Surf group) by intratracheal administration of surfactant (100 mg phospholipid.kg-1 BW), and in the other group by instillations with saline (El/s group). The third group of control mice was treated with saline followed by three doses of surfactant (s/Surf group). After eight weeks, the mice were killed and emphysema was measured by calculating the mean linear intercepts (Lm) of airspaces. The Lm values in the different groups were statistically tested for differences by the Mann-Whitney test. Instillation of pancreatic elastase (El/s group) resulted in an evenly distributed increase in Lm compared with the control group. Administration of surfactant in elastase-treated mice (El/Surf group) resulted in a statistically significant inhibition of airspace enlargement. Although the Lm in the El/Surf group was still higher than in the control group, analysis of histograms of Lm values per field of examination revealed that the Lm distribution in the former group was similar to that of the s/Surf group. The El/s group, on the contrary, showed the presence of many fields with enlarged air spaces. Repeated instillations with saline and/or surfactant had no effect on the Lm.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗

PubMed1992

No advantage for patients who receive splenic irradiation before bone marrow transplantation for chronic myeloid leukaemia: results of a prospective randomized study.

A total of 239 patients with chronic myeloid leukaemia (CML) in chronic phase awaiting bone marrow transplantation (BMT) from an HLA-identical sibling donor were randomized to receive, as part of their conditioning, splenic irradiation (SI+) or no splenic irradiation (SI-). There was no difference between the SI+ and SI- groups regarding the distribution of age, sex, donor/recipient sex combination and blood counts at diagnosis and at BMT. Survival, leukaemia-free survival (LFS), incidence of transplant-related mortality, incidence of rejection and probability of relapse do not differ between the 117 SI+ and the 118 SI- patients at a median follow-up time of 2.5 years (minimum 0.5 years). LFS at 30 months is 56% (SE 5%) for the SI+ and 51% (SE 6%) for the SI- group (p = 0.65). LFS is better for younger patients (less than 25 years), for patients without T cell depletion and for those with a low white blood cell count at diagnosis (less than 30 x 10(9)/l) (p less than 0.05). It is worst for male recipients of a female marrow (p less than 0.05). The incidence of graft-versus-host disease grade greater than or equal to II was higher in the SI+ group, though not significantly. We conclude that routine splenic irradiation prior to BMT for patients with CML is of no benefit and should not be used as a routine procedure.

Adolescent↗

PubMed1992

Quality control of surgical technique in a multicenter, prospective, randomized, controlled study on the surgical treatment of gastric cancer.

To evaluate the effect of lymph node dissection on gastric cancer patients operated upon with curative intent, we are carrying out a multicenter, prospective, randomized, controlled study in the Netherlands. The trial compares conventional gastrectomy to gastrectomy with extended lymph node dissection. In the first four months, a Japanese supervisor attended all the extended surgery and instructed many Dutch surgeons, including the eight consulting surgeons; since then, all extended gastrectomies have been attended by one of the consulting surgeons. The study coordinator attended all conventional cases. This assured that the quality of the extended surgery was as good as the Japanese standard, of which excellent results have been reported. To achieve this quality control, randomization before surgery was obligatory for practical reasons. Curability assessment at laparotomy, however, is done quite objectively with histological proof, except for the judgement of irresectability. Although this has resulted in many non-curative cases being randomized but subsequently not given the allocated surgery, the sample size should be sufficient to allow analysis according to randomization or the initial "intention to treat." This is the first protocol for a multicenter trial in surgical oncology to have such excellent surgical quality control and to assure a quality as high as that in the original report with uniformity in the level of technique. In studies comparing surgical techniques, it is vital that attention should be given to surgical quality control, otherwise survival rates may show little improvement and fail to make any impact on surgical practice.

Adenocarcinoma↗

PubMed1992

Slow response to induction chemotherapy is an indicator of poor survival after bone marrow transplantation for acute lymphoblastic leukemia. The Leukemia Working Party of the European Group of Bone Marrow Transplantation (EBMT).

The prognostic value of diagnosis-remission interval on leukemia-free survival (LFS) after bone marrow transplantation (BMT) was investigated retrospectively in 193 adult patients with acute lymphoblastic leukemia (ALL) transplanted in first remission and reported to the EBMT between 1979 and 1986. Patients achieving remission within 8 weeks of diagnosis ('fast responders') had better LFS after BMT than those with remission after 8 weeks ('slow responders'): LFS at 3 years was 43% vs 32% for fast and slow responders, respectively (p = 0.04). The effect on LFS was particularly severe for slow responders transplanted within 3 months of remission. Only 17% of the slow responders with short remission-BMT interval survived at 3 years. Decreased LFS was caused by both excess of transplant-related mortality and increased relapse incidence. In a multivariate analysis, time intervals (both diagnosis-remission and remission-BMT) were the strongest independent prognostic factor for LFS, probability of relapse and transplant-related mortality. We conclude that the intervals diagnosis-remission and remission-BMT have a strong prognostic value in adult patients with ALL not only for remission duration after conventional treatment, but also for LFS after BMT.

Adolescent↗

PubMed1991

Multiple cDNAs of phosphoenolpyruvate carboxylase in the C4 dicot Flaveria trinervia.

We have isolated and characterized cDNA clones for the leaf-specific C4-phosphoenolpyruvate carboxylase (PEPCase) from the dicotyledonous C4 plant Flaveria trinervia. The isolation of multiple cDNAs indicates that in this plant the C4 isoform is encoded by a small subgroup of the PEPCase gene family. The deduced amino acid sequence reveals a higher degree of similarity to the CAM and C3 isozymes of the dicotyledonous, facultative CAM plant Mesembryanthemum crystallinum than to the C4 PEPCases of monocotyledonous origin.

Amino Acid Sequence↗

PubMed1991

The CMF-regimen. Toxicity patterns following stepwise combinations of cyclophosphamide, methotrexate and fluorouracil.

The contribution of the agents used in the CMF regimen, i.e., cyclophosphamide (CY), methotrexate (MTX) and fluorouracil (FUra), to the development of toxicity was determined in tumor-bearing WAG/Rij rats. Data from untreated (U) rats were compared with data from rats treated with single-agent therapy (C-, M- and F-treatment groups), with data from double-agent therapy (CM-, MF- and CF-treatment groups) and with data from the triple combination: the CMF-treatment group. Doses of agents of interest were the same in all treatment groups. The sequence of administration was (1) CY; (2) MTX and (3) FUra which is similar to clinical treatment with CMF. Systemic levels of CY, MTX and FUra were comparable to those found in patients treated according to the CMF regimen. Toxicity was evaluated by body-weight changes, water and food consumption, white blood cell (WBC) and platelet cell (Pts) counts. With the exception of WBC and Pts nadirs, estimated toxicity parameters reflected toxicity over the whole treatment period of 14 days. The toxicity was generally mild and well tolerated, with one fatality in the M-treatment group. CY was the main contributor to toxicity; it caused both myelotoxicity and gastro-intestinal toxicity. The contribution of FUra was judged to be negligible. MTX + FUra did not increase host toxicity in a synergistic or even an additional fashion. The absence of addition or synergism of toxic side-effects can be explained both by site-specific interactions at the pharmacodynamic level and by interactions at the pharmacokinetic level.

Animals↗

PubMed1991

Pharmacological evaluation of experimental isolated liver perfusion and hepatic artery infusion with 5-fluorouracil.

The intention of this study was to estimate the pharmacological advantage of a clinically applicable method of isolated liver perfusion (ILP) over hepatic artery infusion (HAI) administering various doses of 5-fluorouracil (FUra). FUra concentrations were measured using high-performance liquid chromatography in liver tissue (pigs and rats), hepatic tumor tissue (rats), and in the systemic circulation (pigs) following ILP and HAI. Forty-two pigs and 36 rats were subjected to either ILP or HAI with 20, 40 or 80 mg of FUra/kg of body weight. ILP resulted in significantly increased FUra concentrations in the liver as compared with the results with HAI in rats and pigs. Median areas under the concentration-time curve in liver tissue were 122.7 mumol.g-1.min and 59.9 mumol.g-1.min (40-mg/kg dose-group) and 236.3 mumol.g-1.min and 45.1 mumol.g-1.min (80 mg/kg) for ILP and HAI, respectively in pigs (both P less than 0.05). Systemic plasma areas under the curve were significantly lower for ILP as compared with HAI in 40- and 80-mg/kg dose-groups with 2.2 mumol.ml-1.min and 9.2 mumol.ml-1.min (40 mg/kg; P less than 0.01) and 6.8 mumol.ml-1.min and 43.2 mumol.ml-1.min (80 mg/kg; P less than 0.01) for ILP- and HAI-treated pigs, respectively. In hepatic tumor tissue a dose-dependent increase of mean FUra concentration was found for ILP-treated rats (P less than 0.05). No significant differences were observed in median FUra concentrations in tumor tissue between ILP- and HAI-treated rats (0.66 mumol.g-1 and 0.63 mumol.g-1 for ILP- and HAI-treated groups with 80 mg/kg; P greater than 0.05). The mean FUra concentration tumor/liver ratio was 0.26. In order to clarify the metabolic fate of high-dose FUra, five rats were subjected to HAI with 150 mg of FUra/kg, and hepatic tumor extracts excised at t = 0 min, t = 5 min, and t = 15 min after infusion were analyzed using 19F nuclear magnetic resonance. Catabolite alpha-fluoro-beta-alanine appeared rapidly at t = 5 min and t = 15 min in liver tissue. Significant amounts of the presumed active nucleotides were not detected in tumor tissue. We conclude that ILP is a means to improve selectivity of administration of antitumor agents to the liver, as compared with HAI. The pharmacological advantage of ILP over HAI administering equivalent doses of FUra was not demonstrated in tumor tissue, because of a large differential between liver tissue extraction and tumor tissue extraction of FUra, which was influenced by the mode of administration.

Animals↗