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Biomedical subjects

J Hermans

Publications and source records attributed to J Hermans.

At least 451 records · Page 25Linked to original sources

Peroperative diagnosis and treatment of metastases to the regional lymph nodes in papillary carcinoma of the thyroid gland.

The management of two groups of patients with papillary carcinoma of the thyroid gland (n = 165) was evaluated retrospectively. Total thyroidectomy was the standard procedure in both groups, but the peroperative diagnosis and treatment of metastases to the regional lymph nodes differed. In group 1 (n = 84), only clinically positive lymph nodes were resected, and if residual postoperative 131I uptake was found, an ablation dose of 131I was given. In group 2 (n = 81), all of the tissue in the tracheoesophageal groove was removed routinely at total thyroidectomy and frozen section was done of the lymph nodes lying along the internal jugular vein. If metastases were found, a modified radical dissection of the neck was performed on the affected side. The two patient groups were comparable with regard to risk factors--local tumor stage, age and sex. Almost twice as many patients were found to have metastases to the lymph nodes in group 2. There was no significant difference in the ten year over-all or recurrence free survival time between the two groups. In group 1, there were more recurrences on the explored side of the neck but fewer distant metastases; however, both findings were not significant. In group 2, significantly more instances of hypoparathyroidism and palsy of the accessory nerve were found (p less than 0.05). Thus, when a more extensive search was carried out, more metastases to the lymph node were discovered and treated, but this did not prevent recurrences in the neck nor did it improve survival time. This approach resulted in more postoperative morbidity. There seems to be no justification for prophylactic removal of regional lymph nodes in instances of papillary carcinoma of the thyroid gland, but modified radical neck dissection may be beneficial if clinically suspect regional lymph nodes are present in the lateral part of the neck.

Adenocarcinoma↗

Allogeneic bone marrow transplantation for secondary leukaemia and myelodysplastic syndromes. Leukaemia Working Party of the European Bone Marrow Transplantation Group (EBMTG).

This retrospective survey of the EBMT Leukaemia Working Parking describes 78 patients with myelodysplasia (MDS) or secondary acute myelogenous leukaemia (sAML) who were given an allogeneic bone marrow transplant (BMT). The status of underlying disease at the time of transplantation was prognostic for the two-year disease-free survival which was 60% for patients transplanted in complete remission. Similar results were obtained for those with less advanced MDS (50-64%) who had not received any prior intensive chemotherapy. The results were significantly less favourable for those with more advanced disease who only partially responded to prior intensive chemotherapy (18%) while none of those who either relapsed or were resistant to chemotherapy survived. Allogeneic BMT can therefore be considered as curative treatment for patients with MDS. Patients with sAML who have a histocompatible donor should be given chemotherapy intensive enough to induce complete remission. If this is achieved these individuals have a prognosis comparable to those with de novo AML in first remission after BMT.

Adolescent↗

Plasma spermidine and putrescine as markers of cancer management.

The hypothesis was tested that dying tumor cells release spermidine and putrescine into the bloodstream. Therefore, a rhabdomyosarcoma was implanted in rats, irradiated and its growth and subsequent reduction compared with spermidine and putrescine plasma concentrations of the venous effluent from the tumor side and contralateral side. In the experimental set-up used the hypothesis could not be verified. It appeared that irradiation only, implantation and growth of a tumor only and an irradiated tumor, all caused elevated spermidine and putrescine concentrations in the effluent of both sides in approximately the same order of magnitude, compared to untreated controls.

Animals↗

Distribution of drugs over whole blood: II. The transport function of whole blood for phenytoin.

Phenytoin (DPH) partition between the three main blood compartments, i.e., plasma proteins, erythrocytes, and plasma water, was studied at various concentrations in vitro and in vivo. In vitro, the partition ratio of DPH in a system of erythrocytes in plasma water was 4.5 at concentrations between 0.8 and 100.8 micrograms DPH/ml. In vitro in whole blood (hence, in the presence of plasma proteins), this ratio was approximately 3.9. At 38 degrees C, blank erythrocytes were already in equilibrium with DPH-spiked plasma 3 min after contact, whereas at 20 degrees C, equilibration took 10 minutes or more. By adding blank ultrafiltrate to blood containing DPH, DPH concentrations of blood compartments shifted. It appeared that with the added blank ultrafiltrate, DPH was delivered overproportionally from erythrocytes and less from the protein fraction. In vivo, the elimination half-life of DPH in erythrocytes was 21.4 h and in plasma proteins 67.9 h. These results are similar to those obtained with valproate. It is concluded that erythrocytes have a low affinity for DPH. Their high-capacity transport system, having a "last-come-first-go" mechanism, plays a quantitatively important role in the transport of DPH.

Blood Proteins↗

Significance of tumor invasion and lymph node involvement on the prognosis and selection for surgery of adenocarcinoma of the cardia.

Between 1970 and 1983, 66 patients with adenocarcinoma of the cardia underwent resection in our institute. Hospital mortality within 30 days of surgery was 18.2%. Overall hospital mortality irrespective of time was 27.3%. The 4-year survival rate for all patients excluding overall hospital mortality was 29%. There was a significant difference in cumulative survival between T2 (n = 29) and T3 tumours (n = 15) (P = 0.035). Comparison in this 44-patient group of cumulative survival of patients with negative nodes (N0, n = 13) and positive nodes (N+, n = 31) was also significant (P = 0.01). The application of tumor invasion and lymph node involvement as peri-operative parameters for the selection of patients for resection was evaluated in a retrospective study. Forty-four patients were found eligible to be rearranged in a system using the following clinicopathological parameters: T = 3 versus T = 2 and N+ (positive nodes in N1 and/or N2 groups) versus N0. This system revealed no distinct group of patients who should be withheld from resection according to the criteria held in our institute. Resection provided excellent relief of dysphagia in most patients. The various findings are discussed, and further prospective studies will be needed. At present, in the absence of haematogenous metastases, we prefer surgical resection for all patients whose general condition allows major surgery.

Adenocarcinoma↗

Malignant lymphoma of the gastrointestinal tract and mesentery. A clinico-pathologic study of the significance of histologic classification. NHL Study Group of the Comprehensive Cancer Center West.

A series of 92 malignant lymphomas of the gastrointestinal tract and mesentery obtained from a population-based registry was studied to assess whether the newly defined concept of mucosa-associated lymphoma has clinical relevance. The cases were grouped according to localization; gastric, intestinal, and mesenteric lymphoma. All cases were reviewed histologically, graded according to the Working Formulation, and reclassified according to the Kiel classification, which was modified to include the categories low- and high-grade mucosa-associated lymphoma. Clinical data, as well as staging and follow-up data, were related to both the original diagnosis and the diagnosis after reclassification. The results showed that the distribution of the types of lymphoma is related to site: centroblastic lymphoma was predominant in the stomach, lymphoblastic in the bowel, and follicular centroblastic-centrocytic in the mesentery. Gastrointestinal lymphoma was disseminated in approximately 50% of the patients at presentation. Survival analysis revealed that classification according to the original Kiel classification and grading according to the Working Formulation provided important prognostic information, whereas introduction of mucosa-associated lymphoma as an entity did not. It was concluded that modification of current classifications to include a separate category for mucosa-associated lymphoma is not useful.

Gastrointestinal Neoplasms↗

Diagnosis and treatment of Graves' disease. Results of a survey of Dutch internists.

The results of a survey of Dutch internists on the diagnostics and treatment of Graves' disease is presented. Eighty-five per cent of all participants chose medical treatment for the uncomplicated patient. Radioiodine was reserved for the case of recurrence after medical treatment and after surgery. Surgical treatment was chosen almost exclusively for a larger goitre by 30% of the participants. Large differences in diagnostics and the treatment were not found between the three categories of hospitals: university, teaching, and general non-teaching hospitals.

Adult↗

Treatment of hypothyroidism in The Netherlands. Results of a survey of Dutch internists.

The results of a survey on the treatment of hypothyroidism by Dutch internists, working in different types of hospitals, are described. Except in cases of cardiac complications or long-standing disease at old age most patients were treated in the out-patient clinic. About 50% of the internists chose 25 micrograms of levothyroxine as the initial dose for uncomplicated hypothyroidism. A lower dose (12.5 micrograms) was chosen by one-third of the internists working in teaching hospitals and general hospitals, while 36% of the internists working in university hospitals start with 50 micrograms of levothyroxine. For all variants of the basic case of uncomplicated hypothyroidism the dose was even lower. Adjustment of the dose was usually made at fixed intervals combined with measurement of plasma thyroid hormone levels and clinical parameters. The final substitution dose was generally based on the TSH levels. Anticoagulant drugs were seldom used except in cases of cardiac complications.

Age Factors↗

Nucleotide sequence of cDNA clones encoding the entire precursor polypeptides for subunits IV and V of the photosystem I reaction center from spinach.

Using lambda gt11 expression cloning and immunoscreening, cDNA-containing recombinant phages for subunits IV and V of the photosystem I reaction center were isolated, sequenced and used to probe Northern blots of polyadenylated RNA prepared from spinach seedlings. The mRNA sizes for both components are approximately 1000 and 850 nucleotides, respectively. The 968 nucleotide cDNA sequence and derived amino acid sequence for subunit IV predict a single open reading frame of 231 amino acid residues (25.4 kDa). Comparison with a 13-residue N-terminal amino acid sequence determined for subunit IV suggests a mature protein of 17.3 kDa (154 residues) and a transit sequence of 77 amino acids (8.1 kDa). The corresponding data for subunit V are 677 bp (cDNA), 167 residues for the precursor protein (18.2 kDa), 98 residues for the mature polypeptide (10.8 kDa) and 69 residues for the transit peptide (7.4 kDa). Secondary structure predictions indicate that both proteins possess greatly different transit sequences and that none is membrane-spanning.

Amino Acid Sequence↗

Frequency of infection among patients with rheumatoid arthritis versus patients with osteoarthritis or soft tissue rheumatism.

We compared the frequencies and types of infections that occurred in 448 patients with rheumatoid arthritis (RA) versus those occurring in 185 control patients who had osteoarthritis or soft tissue rheumatism. At least 1 infection developed in 23% of the RA patients and in 27% of the control patients. Using a series of risk factors, we found no substantial difference in the risk of infection in RA patients compared with that in control patients. Some of these factors, such as being female, having poor functional capacity, and receiving glucocorticoid treatment, were associated with different levels of risk for infection, but the levels were similar in RA patients and control patients.

Arthritis, Rheumatoid↗

Microfolding: conformational probability map for the alanine dipeptide in water from molecular dynamics simulations.

A direct attack on the protein-folding problem has been initiated with the free energy perturbation methods of molecular dynamics. The complete conformational probability map for the alanine dipeptide is presented. This work uses the SPC model for the explicit hydration of the dipeptide. Free energy differences for the four observed minima (beta, alpha R, alpha L, C7ax) are given, and the free energy barriers between minima are outlined.

Dipeptides↗

In vivo isolated liver perfusion technique in a rat hepatic metastasis model: 5-fluorouracil concentrations in tumor tissue.

An in vivo method of isolated rat liver perfusion was developed with true vascular isolation and recirculating perfusate. This new surgical technique to temporarily isolate the liver vascularly, and the perfusion procedure are described in depth. Twelve inbred WAG/RIJ rats were subjected to 25 min of normothermic liver perfusion without chemotherapy, and all rats survived the procedure. Hepatic functional and histological integrity were not significantly altered during perfusion. To determine the role of isolated liver perfusion (ILP) as a means of improved targeting of antitumor agents, 5-fluorouracil (5-FU) concentrations were monitored in hepatic tumor and liver tissues and in systemic plasma using high-performance liquid chromatography. Fifty-one rats with hepatic tumors of colonic origin were randomly assigned to one of three dosage groups (20, 40, or 80 mg/kg) receiving 5-FU by ILP, hepatic artery infusion (HAI), or jugular vein infusion (JVI). ILP resulted in significantly increased 5-FU concentrations in liver tissue. However, no significant differences were found in tumor tissue concentrations of 5-FU between the three treatment modalities. 5-FU concentrations in tumor tissue increased as a function of the dose with ILP, HAI, and JVI. ILP was associated with the lowest systemic drug concentrations. The low systemic 5-FU concentrations with ILP suggest a higher maximum tolerable dose. This mode of treatment deserves to be studied further in our model before conclusions can be drawn regarding its therapeutic potential.

Animals↗

DNA flow cytometry and morphometry as prognostic indicators in advanced ovarian cancer: a step forward in predicting the clinical outcome.

In 74 patients with advanced ovarian cancer, the value of DNA flow cytometry and morphometry was evaluated and compared with histological grading and clinical outcome. By means of both DNA flow cytometry and morphometry a clear distinction was found between a favorable group of 15 patients, with a median survival of more than 60 months, and the remaining patients, of whom the majority died during the same follow-up period. The levels of significance for DNA flow cytometry (P = 0.0002) and morphometry (P = 0.0001) with respect to survival of the favorable and unfavorable groups of patients were higher than for histological grading (P = 0.02). In a multivariate analysis it was demonstrated that morphometry proved to be the factor of most relevance for survival, although the effect of DNA flow cytometry was almost as good. Data such as presence of ascites, the size of the residual tumor mass, choice of chemotherapy, FIGO stage, and histological grade were not of additional prognostic relevance in this analysis. It is concluded that both morphometry and DNA flow cytometry are a step forward in identifying favorable and unfavorable groups of patients with advanced ovarian cancer. For the daily practice of management of ovarian cancer patients, morphometry may be an attractive support of visual grading.

Adenocarcinoma↗

Radiotherapy as an alternative to surgery in elderly patients with resectable lung cancer.

From 1978 to 1983, 50 patients with a peripherally located non-small cell tumor of the lung were irradiated with curative intent. These patients were not operated upon because of poor cardiac or pulmonary condition, old age or refusal to operate. Mean age was 74 years, 40 patients being over 70 years of age. All patients had T1-2 N0M0 tumors according to the AJC classification and received 60 Gy to the primary tumor only. The overall response rate was 90%, with 50% complete responses in tumors smaller than 4 cm. The crude overall survival rates were 56% at 2 years and 16% at 5 years, with a median survival of 27 months. Age did not influence survival. There was a strong correlation of survival to tumor size, with 5-year survival rates of 38, 22, 5 and 0% in tumors with diameters of less than or equal to 2, 2-3, 3-4 and greater than 4 cm respectively. Only 5 out of 20 complete responders had a local recurrence, the 5-year survival in this group was 42%. These results compared favorably to a group of 86 patients over 70 years of age who were selected for operation in the same hospital. The 2- and 5-year survival rates in these patients were 48 and 26% respectively, median survival being 23 months. We conclude that in patients over 70 years of age with resectable lung cancer, radiotherapy with curative intent should be offered as an alternative to operation, especially if the tumor is not larger than 4 cm.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

The effect of radiotherapy on dysphagia and survival in patients with esophageal cancer.

A group of 127 patients with esophageal cancer treated with radiotherapy at different dose levels was retrospectively analysed. It was found that 70.5% of the patients showed improvement of dysphagia and that 54% remained palliated with respect to food passage until their death. The two major prognostic variables with respect to the palliative effect on dysphagia as well as survival were the passage score and the radiation dose. Patients with severe dysphagia (PASS 0 or 1) had a median actuarial DFI and SURV of 3.7 and 6.4 months, respectively, in contrast to 16.0 and 8.7 months for patients who were able to use (semi)solid food (PASS 2 and 3). The median actuarial DFI and SURV of patients treated with a relatively low dose (less than 50 Gy in 5 weeks) were 2.5 and 4.8 months, respectively, compared to 10.1 and 8.3 months, respectively, for patients treated with a relatively high dose.

Adenocarcinoma↗

Multivariate analysis of survival in differentiated thyroid cancer: the prognostic significance of the age factor.

A retrospective analysis of tumour and patient characteristics was performed in 202 patients with papillary (n = 132) or follicular (n = 70) thyroid carcinoma, in order to identify prognostic factors related to survival. The following facts were found to be unfavourably related to survival: follicular histology, extrathyroidal growth of the primary tumour (stage pT4), regional lymph node involvement (stages pN1-3), presence of distant metastases at diagnosis (stage pM1), male sex (in papillary cancer) and old age (only death due to thyroid tumour was evaluated). For 190 patients sufficient material was available to permit extensive histopathological investigation. In patients with papillary cancer the presence of small anaplastic foci and/or greater than 25% solid structures (n = 18) was correlated with a reduced survival rate. Our study underlines the importance of distinguishing, histologically, between papillary and follicular cancer and in addition demonstrates the prognostic value of histological grade in papillary (but not follicular) carcinoma. We applied Cox's proportional hazard model to the survival data of these 190 patients and, after stage grouping, found that tumour stage (locoregional vs. advanced disease) was the most important prognostic factor. The second most important factor was the histological (sub)type (well differentiated papillary carcinoma vs. moderately differentiated papillary carcinoma and follicular carcinoma). Age at diagnosis and sex appeared to be of lesser importance. Therefore our study does not recommend the use of age as a guide for therapeutical decisions in differentiated thyroid cancer.

Adenocarcinoma↗