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Biomedical subjects

J Hermans

Publications and source records attributed to J Hermans.

At least 307 records · Page 17Linked to original sources
PubMed1993

Molecular dynamics study of structure and stability of a model coiled coil.

This paper employs methods used earlier to study helix propensity in a model alpha-helix. The methods are extended to simulations of a motif structure of the alpha-helical coiled coil, i.e., a structure with a simple amino acid sequence, containing only alanine, leucine, and valine, with leucine and valine forming hydrophobic contacts in the helix interface (positions "d" and "a"). Dynamic simulations of the model coiled-coil structure reproduce characteristic features of the coiled-coil motif seen in experimental studies. Free energy simulations were used to assess the change in stability of the model when a leucine pair or a valine pair in the helix interface was replaced with an alanine pair. A leucine pair at position d was found to contribute 3.4 kcal/mol to the stability of the coiled coil relative to an alanine pair, and a valine pair at position a was found to contribute 0.8 kcal/mol relative to an alanine pair. The value for the leucine pair agrees with reports in two experimental studies with molecules having different amino sequence. The value for the valine pair is reasonable given the smaller size of the valine side chain and the intrinsic low helix propensity of valine. No experimental value was available for comparison.

Amino Acid Sequence↗
PubMed1993

Randomized trial comparing cryopreserved cultured epidermal allografts with hydrocolloid dressings in healing chronic venous ulcers.

BACKGROUND: Cultured epidermal allografts have been successfully used to treat a variety of wounds. Their postulated mechanism of action is through release of cytokines that stimulate epithelialization. On the basis of previous experience we expected ulcers treated with cryopreserved cultured allografts (CCAs) to be healed by 6 weeks. Hydrocolloid dressings (HCDs) have also been reported to be effective in the treatment of venous ulcers. OBJECTIVE: Our purpose was to compare the effectiveness of CCAs with HCDs in healing chronic venous ulcers. METHODS: Forty-three patients with 47 ulcers were enrolled in a randomized controlled trial. Ulcers not healed by 6 weeks were changed to the other treatment. RESULTS: No difference in the number of healed ulcers between the two groups was observed at 6 weeks. Healing rate, percent reduction of initial ulcer size, and radial progression toward wound closure were significantly greater for CCAs than for HCDs. Pain relief was not significantly different. CONCLUSION: CCAs achieve more rapid healing and greater reduction in ulcer size than HCDs.

Adult↗
PubMed1993

Pelvic failure rate and radiation toxicity in relation to total dose of radiation alone for the treatment of cancer of the uterine cervix.

Seventy-four patients presenting between 1978 and 1989 with carcinoma of the uterine cervix were analysed to compare our results with the published literature, especially with regard to the pelvic failure rate and radiation toxicity. Overall 5-year survival reached 41%. Overall 2-year survival rate for Stage IIB was 85% and Stage IIIB was 32%. For Stage IIB the results agreed with those reported in the literature. Pelvic control was related to total dose and the application of intracavitary irradiation. For Stage IIIB the results were disappointing, partly due to a large number of bulky tumours and also to a relatively low paracentral dose and dose to the pelvic side wall. Percentages of radiation side-effects were low compared with those reported in the literature, probably also due to the relatively low total dose.

Brachytherapy↗
PubMed1993

Nuclear DNA content and morphological characteristics in the prognosis of adrenocortical carcinoma.

Prognostic factors are needed for the management of patients with adrenocortical tumours. For this reason, the nuclear DNA content of patients with adrenocortical tumours was analysed by flow cytometry. The relationships between nuclear DNA content, histological indices, and clinical parameters were studied. DNA ploidy could be evaluated in 54 carcinoma and 31 adenoma patients. Twenty-one (68%) of the adenomas, and 6 (11%) of the carcinomas, were DNA diploid. Hypo/Hyperdiploidy was found in 5 (16%) of the adenomas, and 15 (28%) of the carcinomas. The remaining patients had a DNA index above 1.40. A shorter survival was found in patients with diploid carcinomas (P < 0.05). A longer disease-free survival was seen in patients with hypo/hyperdiploid carcinomas (P < 0.05). Nuclear DNA content was not related to the histological index, nor to clinical parameters. We conclude that nuclear DNA content is related to (disease-free) survival of patients with adrenocortical carcinomas. An adenoma-carcinoma sequence may be present in the adrenal cortex. In adrenocortical tumours ploidy evolution appears to be different than that observed in other solid tumours.

Actuarial Analysis↗
PubMed1993

Correlation of 99Tcm-sestamibi SPECT with coronary angiography in general hospital practice.

One hundred and twenty-eight patients had a stress test with sestamibi injection and a coronarography within 2 months of the sestamibi study. Sestamibi studies were reconstructed using Hanning 0.65 and Wiener 1.0 filters; the latter improved the results significantly (P < 0.05). Significant correlations were found between sestamibi and coronarography: the sensitivity was 0.967 and the specificity was 0.711. Thus sestamibi is a very good compound, with excellent imaging quality, which is very sensitive for mild defects, even more sensitive than coronarography. Thorough studies of discrepancies show that they could be explained by reductions in coronary flow or myocardial reserve, even when the large epicardial vessels are disease free as occurs in various coronary involvements. A follow-up of positive patients with sestamibi and negative coronarography is absolutely necessary since this group of patients represents a 'risk' group. Moreover, sestamibi single photon emission computed tomographic accuracy is highly dependent on filter choice.

Adult↗
PubMed1993

Islet cell hormone release immediately after human pancreatic transplantation. A marker of tissue damage associated with cold ischemia.

Pancreatic graft procurement, preservation, and transplantation surgery may result in damage to and loss of the integrity of endocrine cells and consequently in leakage of cell products into the insular vascular capillaries. Thus, the amount of alpha-, beta-, and pancreatic polypeptide (PP) cell products released into the vascular space of the recipient immediately after graft reperfusion may reflect islet cell injury. To test this hypothesis, we assessed glucagon, PP, C-peptide, and insulin levels in a prospective study of 22 consecutive renal-pancreatic transplantations. Transplantation-related parameters were used to account for differences in hormone release. Five grafts were preserved using Euro-Collins preservation fluid and 17 grafts were preserved using University of Wisconsin solution (UW). The first sign of a reinstalled physiological axis was the decrease of the blood glucose concentration after a median duration of 40 min (range 5-90 min) and the association of the recipient's ambient blood glucose levels with insulin release between 25 and 180 min after reperfusion. The delay period before a fall in blood glucose was observed correlated with cold ischemia time (rs = 0.73, P < 0.001, n = 21). An immediate and marked increase in plasma levels of glucagon (from 180 +/- 18 to 585 +/- 99 ng/L, mean +/- SEM), PP (from 57 +/- 8 to 122 +/- 13 pmol/L), C-peptide (from < 0.06 +/- 0.02 to 5.43 +/- 0.63 nmol/L), and insulin (from 0.15 +/- 0.21 to 2.05 +/- 0.26 nmol/L) was observed. C-peptide release correlated with glucagon (r = 0.76, P < 0.001) and PP (r = 0.60, P < 0.01). The hormone release was compared with computed tomography scans that were performed in the immediate postoperative period in 15 UW-preserved allografts. The diameter of the pancreatic head was increased and ranged from 4.5 to 7.7 cm (mean 6.2 cm). Peroperative C-peptide release significantly correlated with morphological graft changes reflected by the pancreatic head diameter (r = 0.58, P = 0.02). In a stepwise multiple regression analysis, cold ischemia time was a significant factor for the release of PP (r2 = 0.18, P = 0.049) and C-peptide (r2 = 0.35, P = 0.004). We suggest that peroperative hormone release reflects endocrine tissue damage. Furthermore, cold ischemia time may jeopardize the pancreatic allograft after relatively short preservation times, even when UW is used.

Adult↗
PubMed1993

Barrier function parameters in various keratinization disorders: transepidermal water loss and vascular response to hexyl nicotinate.

In this study, we characterized the stratum corneum barrier function in 39 patients with various keratinization disorders (autosomal dominant ichthyosis vulgaris [ADI] [n = 7], X-linked recessive ichthyosis [XRI] [n = 6], autosomal recessive congenital ichthyosis [CI] [n = 10], dyskeratosis follicularis [Darier's disease; DD] [n = 8], erythrokeratoderma variabilis [EKV] [n = 8]), and 21 healthy volunteers, using two non-invasive methods: transepidermal water loss (TEWL) measuring outward transport of water through the skin by evaporimetry, and the vascular response to hexyl nicotinate (HN) penetration into the skin as determined by laser-Doppler flowmetry. Significantly increased TEWL values were found on the volar forearm in all three forms of ichthyosis, compared with the healthy control group, with the highest TEWL values in the CI group. The penetration of HN on the volar forearm was accelerated in patients with ADI, XRI and CI, as indicated by a shorter lag time (t0) between HN application and initial vascular response. However, differentiation between CI and the other ichthyoses was not possible by this method. When using both methods in DD and EKV, no differences compared with the healthy controls could be detected on the volar forearm, where the skin was principally unaffected; only the measurements from the affected skin on alternative sites demonstrated significantly increased TEWL values. In ADI and CI, however, normal-appearing skin also showed impaired values. We conclude that both TEWL and the vascular response to penetration of HN are suitable methods to monitor the skin barrier function in keratinization disorders, and are helpful in discriminating between these disorders.

Adult↗
PubMed1993

Skin barrier function in healthy volunteers as assessed by transepidermal water loss and vascular response to hexyl nicotinate: intra- and inter-individual variability.

This study assesses the variability of two non-invasive methods of measuring stratum corneum barrier function in vivo. Transepidermal water loss (TEWL), and the vascular response to hexyl nicotinate (HN) penetration as determined by laser-Doppler flowmetry, were measured in a group of 21 healthy volunteers. Each time profile of the vascular response to HN penetration was analysed using the following parameters: the baseline cutaneous blood flow, the lag-time between application and initial response (t0), the time between application and maximum response (tmax), the maximum response, and the slope of the curve. TEWL measured on the left volar forearm showed a normal range of 3.9-7.6 g/m2h and a small inter-individual variability [coefficient of variation (CV) 19.4%]. TEWL values at three other forearm sites did not show differences of clinical importance compared with the left volar forearm. The parameters of the vascular response to HN penetration spanned a wider normal range than the TEWL values (CV between 33 and 52%). Repeat measurements after a 1-2 month interval showed highly reproducible individual TEWL values. The mean difference between first and second measurements was only 0.03 g/m2h; the relative difference 0.6%. The intra-individual reproducibility of t0 and tmax. for HN penetration was also high (relative differences of 2.8 and 3.1%, respectively). The other vascular response parameters were less reproducible (relative differences of 6.9-18.6%). We conclude that TEWL and selected parameters of HN penetration, as non-invasive tests of the stratum corneum barrier function, yield reproducible results and are hence useful for investigations assessing the skin barrier function in various disorders.

Adolescent↗
PubMed1993

On naevi and melanomas in dysplastic naevus syndrome patients.

Cutaneous melanoma may occur as isolated, so-called 'sporadic' cases or in association with multiple atypical naevi and in familial clusters, in which case it is referred to as the familial dysplastic naevus syndrome (DNS). In this retrospective study (a) the number and body distribution of naevocytic naevi and (b) the body distribution of malignant melanoma (MM) in individuals with familial DNS were compared in order to study their association. In 45 patients with familial DNS aged 20-39 years naevus counts on trunk and lower extremities were compared with melanoma data and distributions from a second group of 43 patients from the same DNS families aged 12-66 years. Men had significantly more naevi of a size > or = 2 mm or > or = 5 mm on the back than women (P = 0.02). Women showed a tendency towards a greater number of naevi on the lower extremities than men, but in women no significant difference in naevi between the lower extremities and the back was found. The total number of naevi on the trunk and lower extremities in familial DNS patients was higher than that in the general population. In conclusion, it was found that predilection sites for melanoma in familial DNS patients of both sexes correspond with the distribution of naevi; in males naevi and melanoma counts and percentage distributions were higher on the back, in females both the back and the lower extremities were affected. These findings strongly suggest an association between naevus distribution and melanoma occurrence and site in familial DNS, analogous to earlier reports on sporadic melanoma.

Adolescent↗
PubMed1993

The evaluation and interpretation of cervical cytology: application of the likelihood ratio concept.

The Papanicolaou smear (Pap test), used for the detection and prevention of neoplastic lesions of the cervix, is known to have both false negative and false positive results. Proper handling of the diagnostic uncertainty resulting from these errors demands quantification of flaws. Traditionally, sensitivity, specificity and predictive values are used for that aim. In this study another approach is advocated, namely the use of the likelihood ratio. For cervical cytology this ratio is the quotient of the probability of a Pap class within the diseased population to the probability of that same Pap class within the non-diseased group. This approach enables the characterization of each Pap class separately, and is therefore much better for clinical interpretation of the result. It is also a superior approach for quality assessment.

Female↗
PubMed1993

Bone marrow transplantation in Europe: major geographical differences. The European Group for Bone Marrow Transplantation [EBMT].

In 1991 171 teams in 21 European countries performed 4976 bone marrow transplants. There were 1829 transplants from an HLA-identical sibling donor, 101 from a nonidentical family member, 30 from a twin, 217 from an unrelated volunteer donor and 2799 autologous transplants. Indications for transplants were leukaemias in 2569 (52%), lymphoproliferative disorders in 1472 (30%), solid tumours in 549 (11%), aplastic anaemia and thalassaemia in 261 (5%), inborn errors in 97 and miscellaneous disorders in 28 patients. There are marked differences between the participating European countries. They relate to absolute numbers, indications and techniques. Less than 10 transplants per 10-million inhabitants are performed in Eastern European countries. Ten to fifty transplants per 10-million inhabitants are done in two, 50-100 transplants per 10-million inhabitants in five, 100-200 transplants per 10-million inhabitants in eight countries and more than 200 per 10-million inhabitants in one country (P < 0.01). The number of transplant teams ranges from less than one to twelve per 10-million inhabitants (P < 0.01). For the continent it becomes 3.3 per 10-million inhabitants. The reasons for these differences are not explained by this survey. The most likely explanation for the differences in transplant activity is availability of transplant beds, trained staff and resources. Bone marrow transplants are expensive. However, the demand is increasing and will increase further with the routine availability of unrelated volunteer donors. Clearly, criteria are required in Europe to define the indications and solutions to meet the legitimate requirements for transplantation in the various regions of Europe.

Bone Marrow Transplantation↗
PubMed1993

Duration of illness in Huntington's disease is not related to age at onset.

The age at onset and duration of illness were studied in patients with Huntington's disease in the Leiden Roster which at 1 July 1990 contained 2787 patients. Of 1106 patients, 800 deceased and 306 alive, the age at onset was known. The median duration was 16.2 (range 2-45) years. In contrast to the current opinion, the median duration was independent of the age of onset. The median duration in juvenile Huntington's disease was 17.1 years, which is much longer than reported in the literature, and comparable with the categories for the age of onset of 20-34 and 35-49 years. Only in the group where onset was over 50 years of age was the median duration somewhat shorter (15.6 years), which can be ascribed to unrelated causes of death. As age of onset and duration of illness are not related, at least two mechanisms to determine the clinical course have to be postulated: one for age of onset and another for duration of illness. Duration was shorter for males, especially for those with an affected father.

Adolescent↗
PubMed1993

Palliative pamidronate treatment in patients with bone metastases from breast cancer.

PURPOSE: An open, randomized study was performed to assess the effects of supportive pamidronate treatment on morbidity from bone metastases in breast cancer patients. PATIENTS AND METHODS: Eighty-one pamidronate patients and 80 control patients were monitored for a median of 18 and 21 months, respectively, for events of skeletal morbidity and the radiologic course of metastatic bone disease. The oral pamidronate dose was 600 mg/d (high dose [HD]) during the earliest study years, then changed to 300 mg/d (low dose [LD]) because of gastrointestinal toxicity. Twenty-nine of 81 pamidronate (HD/LD) patients first received 600 mg/d and were then changed to 300 mg/d; 52 of 81 pamidronate LD patients received 300 mg/d throughout the study. Tumor treatment was unrestricted. RESULTS: An overall intent-to-treat analysis was performed. In the pamidronate group, the occurrence of hypercalcemia, severe bone pain, and symptomatic impending fractures decreased by 65%, 30%, and 50%, respectively; event-rates of systemic treatment and radiotherapy decreased by 35% (P < or = .02). The event-free period (EFP), radiologic course of disease, and survival did not improve. Subgroup analyses suggested a dose-dependent treatment effect. Compared with their controls, in pamidronate HD/LD patients, events occurred 60% to 90% less frequently (P < or = .03) and the EFP was prolonged (P = .002). In pamidronate LD patients, event-rates decreased by 15% to 45% (P < or = .04). Gastrointestinal toxicity of pamidronate caused a 23% drop-out rate, but other cancer-associated factors seemed to contribute to this toxicity. CONCLUSION: Pamidronate treatment of breast cancer patients efficaciously reduced skeletal morbidity. The effect appeared to be dose-dependent. Further research on dose and mode of treatment is mandatory.

Bone Neoplasms↗
PubMed1993

Adjuvant therapy after curative resection for gastric cancer: meta-analysis of randomized trials.

PURPOSE: An overview is presented of reports published since 1980, in which postoperative adjuvant chemotherapy is compared with surgery alone for patients with gastric cancer. A MEDLINE literature review yielded 123 reports, 14 of which were relevant randomized trials; data from 11 of these trials were (or became) available for analysis of crude mortality odds. These 11 trials included 2,096 patients. METHODS: Odds ratios were calculated by comparing the adjuvant treatment arm with the observation-only arm. Those odds ratios that could be considered homogeneous yielded an estimated common odds ratio of 0.88 (95% confidence interval [CI], 0.78 to 1.08), which was slightly, but far from significantly, in support of adjuvant treatment. RESULTS: The results confirm the common opinion that the adjuvant chemotherapy regimens prescribed in these trials, although effective in phase II studies, do not improve survival. Furthermore they indicate that postoperative chemotherapy in general offers no additional survival benefit for patients with curatively resected gastric cancer. CONCLUSION: In conclusion, at present, postoperative chemotherapy cannot be considered as standard adjuvant treatment. New trials of adjuvant therapy for gastric cancer must include a no-treatment control arm.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Management of vulvar carcinoma radiation toxicity, results and failure analysis in 44 patients (1980-1989).

A retrospective analysis was performed on 44 patients with squamous carcinoma of the vulva (1980-1989). Patients were divided into two subgroups, group I (n = 39) treated with curative intent with surgery alone or with surgery combined with radiotherapy and group II (n = 5) treated with palliative intent with irradiation alone. The five-year cancer-specific survival rate for group I was 65%. Although this is a group of elderly patients, it was concluded that curative therapy should be aggressive and concessions which lead to suboptimal treatment should be avoided. It is essential to achieve free surgical margins. If it is decided to irradiate, no concessions should be made with respect to dose or overall treatment time. Poor results were obtained in the group treated with palliative intent with a six week treatment scheme of five fractions/wk. All irradiated patients suffered from moist desquamation as acute side-effect. Serious late side-effects did not occur.

Adult↗
PubMed1993

Splenic irradiation before bone marrow transplantation for chronic myeloid leukemia: update of a prospective randomized study.

Two hundred and twenty-nine patients with chronic myeloid leukaemia in chronic phase awaiting bone marrow transplantation from an HLA-identical sibling donor were randomized as part of their conditioning, to receive splenic irradiation (SI+, 115 patients), or not (SI-, 114 patients). Both groups were identical in regard to age, sex, donor/recipient sex combination and disease activity. Survival, leukaemia-free survival, incidence of transplant-related mortality, acute and chronic graft versus host disease, incidence of rejection and probability of relapse were not different in either groups at a median follow-up time of 4.5 years (minimum follow-up 2 years). Recovery of peripheral white blood cell counts to 1 x 10(9)/l but not of platelet counts to 50 x 10(9)/l was significantly faster in patients with SI+ (21 vs 24 days). This small benefit does not justify routine splenic irradiation prior to BMT, in CML.

Adolescent↗