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Biomedical subjects

H Hoekstra

Publications and source records attributed to H Hoekstra.

13 recordsLinked to original sources

Multi length scale analysis of the microstructure in sticky sphere dispersions during shear flow.

The effect of shear flow on the microstructure in a weakly aggregated suspension is investigated. Monodisperse small silica particles with a grafted layer of 1-octadecanol are dispersed in n-tetradecane, yielding a thermoreversible sticky sphere model suspension. A combination of small angle light scattering and ultra small and small-angle X-ray scattering techniques have been used, in situ and time resolved, to study the flow-induced anisotropy of the microstructure. In this manner, the length scales from the single particle size to that of the spatial organization of the aggregates can be covered. Harmonic expansion of the structure factor demonstrates that anisotropy develops in the microstructure on all relevant length scales. Possible real space interpretations of the scattering information are discussed in conjunction with implications for the nonlinear rheological behavior.

Journal Article↗

Inclusion of malignant fibrous histiocytoma in the tumour spectrum associated with hereditary non-polyposis colorectal cancer.

Sarcomas, including the malignant fibrous histiocytomas (MFHs), are not known to be part of the tumour spectrum of hereditary non-polyposis colorectal cancer (HNPCC) as epidemiologically established. Therefore, occurrence of MFH in an HNPCC family may very well be coincidental. HNPCC is associated with germline mutations in DNA mismatch repair genes, including the MSH2 gene. We analysed an MFH diagnosed in a 45-year-old male HNPCC patient carrying a germline MSH2 mutation for HNPCC-associated molecular characteristics, to investigate a possible relationship between the tumour and that mutation. DNA analysis revealed microsatellite instability and loss of one MSH2 copy, and immunohistochemistry showed absence of nuclear MSH2 protein staining. To investigate whether this is a common finding in MFH, microsatellite instability and nuclear MSH2 protein staining was tested for in 5 and 6 sporadic MFHs, respectively. None showed microsatellite instability and all stained positively for MSH2. Together, these findings show that in rare cases, MFH may be part of the HNPCC tumour spectrum.

Adenocarcinoma↗

Lactobacillus GG administered in oral rehydration solution to children with acute diarrhea: a multicenter European trial.

BACKGROUND: The probiotic Lactobacillus GG is effective in promoting a more rapid recovery of acute, watery diarrhea in children with rotavirus enteritis. Very limited information is available, however, on the potential role of such agents in non-rotaviral diarrheal episodes. Furthermore, no evidence is available concerning the efficacy of Lactobacillus GG administered in the oral rehydration solution during oral rehydration therapy. A multicenter trial was conducted to evaluate the efficacy of Lactobacillus GG administered in the oral rehydration solution to patients with acute-onset diarrhea of all causes. METHODS: Children 1 month to 3 years of age with acute-onset diarrhea were enrolled in a double-blind, placebo-controlled investigation. Patients were randomly allocated to group A, receiving oral rehydration solution plus placebo, or group B, receiving the same preparation but with a live preparation of Lactobacillus GG (at least 10(10) CFU/250 ml). After rehydration in the first 4 to 6 hours, patients were offered their usual feedings plus free access to the same solution until diarrhea stopped. RESULTS: One hundred forty children were enrolled in group A, and 147 in group B. There were no differences at admission between the groups in age, sex, previous types of feeding, previous duration of diarrhea, use of antibiotics, weight, height, weight-height percentile, prevalence of fever, overall status, degree of dehydration, and percentage of in- versus outpatients. Duration of diarrhea after enrollment was 71.9 +/- 35.8 hours in group A versus 58.3 +/- 27.6 hours in group B (mean +/- SD; P = 0.03). In rotavirus-positive children, diarrhea lasted 76.6 +/- 41.6 hours in group A versus 56.2 +/- 16.9 hours in groups B (P < 0.008). Diarrhea lasted longer than 7 days in 10.7% of group A versus 2.7% of group B patients (P < 0.01). Hospital stays were significantly shorter in group B than in group A. CONCLUSIONS: Administering oral rehydration solution containing Lactobacillus GG to children with acute diarrhea is safe and results in shorter duration of diarrhea, less chance of a protracted course, and faster discharge from the hospital.

Acute Disease↗

Protein synthesis rate measured with L-[1-11C]tyrosine positron emission tomography correlates with mitotic activity and MIB-1 antibody-detected proliferation in human soft tissue sarcomas.

Protein synthesis rate (PSR) can be assessed in vivo using positron emission tomography with L-[1-11C]tyrosine (TYR-PET). Biological activity of soft tissue sarcomas (STS) can be measured in vitro by the mitotic rate and number of proliferating cells. In STS the grade of malignancy, in which the mitotic index plays a major role, is considered to be the major standard in predicting biological tumour behaviour. This study was designed to test the validity of TYR-PET in relation to different histopathological features. In 21 patients with untreated STS, the PSR was measured using TYR-PET. The number of mitoses was counted and tumours were graded according to the grading system of Coindre et al. (Cancer 1986; 58:306-309). Proliferative activity was assessed by immunohistological detection of the Ki-67 nuclear antigen using MIB-1 monoclonal antibody. To test the association between the PSR and these tumour parameters, a correlation analysis was performed. A significant (P<0.05) correlation was found between PSR and the Ki-67 proliferation index (R = 0.54), and between PSR and mitotic rate (R = 0.64). There was no correlation between PSR and tumour grade. The present study in malignant soft tissue tumours relates in vivo tumour metabolism as established with TYR-PET to tumour activity measured in vitro and indicates that the non-invasive method of TYR-PET can estimate the mitotic and proliferative activity in STS.

Adult↗

Povidone-iodine liposomes--an overview.

In recent years, liposomes have been increasingly explored as novel drug delivery systems, and several liposome-based drug products have been approved in Europe, the USA and Japan. Depending on size, composition and surface characteristics, liposomes interact specifically with biological structures. Liposomal drug products provide a topical activity at the desired locus of action and are deemed more effective and less toxic than conventional drug formulations. The combination of povidone-iodine (PVP-I) and liposomes unites the exceptional microbicidal activity of the antiseptic substance with the excellent tolerability and lack of immunogenicity of liposomes; in addition, liposomes provide a moist molecular film for the wound environment. The multilamellar vesicles act as microreservoirs hence prolonging the release of the active ingredient. Although no commercial product for repeated application on the eye is currently available, PVP-I has been used in ophthalmology not only for pre- and postoperative antisepsis, but also for the treatment of bacterial and viral conjunctivitis and for prophylaxis against ophthalmia neonatorum. For these indications, liposomal formulations with 2.5 and 5.0% PVP-I were developed. These eye drops are isotonic with tear fluid at pH 6. First in vitro tests demonstrated an excellent antimicrobial efficacy, and a placebo-controlled clinical study on volunteers showed a very good local tolerability. A study on rabbits demonstrated positive results of the PVP-I liposome eye drops compared to placebo and the broadspectrum antibiotic Polyspectran in a standardized model of Staphylococcus aureus deep eye infection. The other aim is a well-tolerated liposomal PVP-I hydrogel for improved antiseptic wound treatment with moisturizer. It has been reported that liposomes are enriched at the wound bottom for direct action against infection and support of wound healing. An animal study on the efficacy and tolerability of different formulations of a hydrogel with PVP-I liposomes in deep dermal burn wounds has indicated an outstanding quality of wound healing with smooth granulation tissue, less inflammation, less wound contraction and no hyperkeratotic reactivity, especially with the 3% PVP-I liposome formulation.

Administration, Cutaneous↗

Improving the palatability of oral rehydration solutions has implications for salt and water transport: a study in animal models.

It is believed that improving the taste of oral rehydration solutions (ORSs) might lead to greater patient acceptability. A pilot trial showed that replacing glucose with sucrose and increasing the citrate concentration at the expense of chloride improves palatability. However, the transport implications of such modifications are not known. Three hypotonic experimental ORSs (Suc/cit-ORS, 211 mosmol/kg; Suc/Cl-ORS, 224 mosmol/kg; and Glu-ORS, 224 mosmol/kg) were compared with a standard European ORS (Euro-ORS, 265 mosmol/kg) by in vivo perfusion of entire rat small intestine in normal adult rats and rotavirus-infected neonates. All ORSs were of identical sodium, potassium, chloride, and citrate content except that in the Suc/cit-ORS, chloride was removed in favor of increased citrate, and the chloride concentration in Euro-ORS was higher than in the others. Suc/cit-ORS and Suc/Cl-ORS had glucose partially replaced by sucrose while Glu-ORS and Euro-ORS contained only glucose. In normal small intestine, water absorption was greater from Glu-ORS than Suc/cit-ORS or Euro-ORS, although water absorption was similar from Suc/cit-ORS and Suc/Cl-ORS. In the rotavirus model, Glu-ORS produced more water absorption than Euro-ORS or either sucrose ORS. In both models, Suc/cit-ORS caused sodium and chloride secretion. Glucose absorption was similar from all ORSs. These findings indicate that attempts to improve ORS palatability by adding sucrose or increasing citrate at the expense of chloride would incur a significant penalty in terms of salt and water absorption.

Animals↗

Reconstruction of human skin from glycerol-preserved allodermis and cultured keratinocyte sheets.

The aim of this project was to reconstruct human skin from glycerol-preserved dermis and layers of cultured keratinocytes for use in the treatment of deep burns and ulcers. Glycerol-preserved cadaver skin from the Euro Skin Bank was treated with Dispase II or PBS, under various conditions, to find the best method of retaining the physical structure of the dermis while removing the epidermis and remnants of dead dermal cells which might provoke an allogeneic reaction in a graft recipient. Monoclonal antibodies LH39 and LH7.2, with specificity for basement membrane determinants, showed that treatment with Dispase II resulted in separation of the epidermis from the dermis with concomitant loss of all cellular elements from the dermal layer (as judged by H and E staining). However, when sheets of cultured keratinocytes were applied to the treated dermis and cultured for several days, the keratinocytes attached and regenerated a new basement membrane.

Cells, Cultured↗

Collaborative study of the International Office of Cocoa, Chocolate and Sugar Confectionery on Salmonella detection from cocoa and chocolate processing environmental samples.

A comparative collaborative study was performed in 13 laboratories to evaluate the use of motility enrichment on Modified Semisolid Rappaport-Vassiliadis medium for rapid Salmonella detection from food-processing environmental samples. Artificially contaminated chocolate scrapings and naturally contaminated cocoa bean dust samples were used in the study. Pre-enrichment was performed in buffered peptone water with added casein and malachite green oxalate. Motility enrichment was compared with a conventional cultural procedure using Rappaport-Vassiliadis broth and selenite cystine broth as selective enrichment. The productivity of motility enrichment was 93.5% compared to a productivity of the cultural procedure of 92%. Statistical analysis showed that there was no significant difference between the two procedures. Modified Semisolid Rappaport-Vassiliadis medium is a sensitive and simple diagnostic tool for the microbiological safety evaluation of food-processing environments.

Cacao↗

Are complications in intraoperative radiation therapy more frequent than in conventional treatment?

To evaluate whether intraoperative radiation therapy (IORT) results in higher complication rates than conventional radiotherapy, 119 patients were studied who entered four prospectively randomized clinical trials that compared IORT with conventional therapy. Malignant neoplasms included 33 gastric carcinomas, 35 retroperitoneal sarcomas, 22 resectable pancreatic cancers, and 29 unresectable pancreatic cancers. One hundred thirty-six complications developed among 66 patients who received conventional therapy, and 108 complications developed among 53 patients who received IORT. There was no statistical significance between treatment groups with respect to the overall incidence of complications. Analysis of types of complications by tumor type using Fisher's exact test revealed only one significant complication: an increased rate of sepsis among the patients with retroperitoneal sarcoma who received conventional therapy compared with their IORT cohorts. The overall complication rate associated with IORT was equivalent to conventional radiotherapy in the treatment of these malignant neoplasms and supported the use of IORT where clinically indicated.

Abdominal Neoplasms↗

Delivery of intraoperative radiation therapy after pneumonectomy: experimental observations and early clinical results.

Intraoperative radiation therapy (IORT) is capable of delivering high doses of radiation to mediastinal structures while sparing lung parenchyma, heart, and other locoregional tissues. A canine model of pulmonary resection and IORT was investigated by performing a pneumonectomy in 15 adult foxhounds followed by 0 cGy, 2,000 cGy, 3,000 cGy, 4,000 cGy. No clinical complications developed in 4 animals in the 2,000-cGy group. However, 2 of the 8 animals given a high dose died of esophageal hemorrhage or carinal necrosis. Esophagitis occurred in 10 of 12 animals, and none of the animals experienced bronchial stump dehiscence. In a limited Phase I protocol, 4 patients with non-small cell lung cancer were treated with resection and 2,500 cGy of IORT to two separate ports encompassing the superior and inferior mediastinum. Two patients experienced life-threatening bronchopleural fistulas, and 2 patients died as a consequence of esophageal problems. One patients had recurrence with brain metastases, and the 1 long-term survivor is free from disease. As opposed to the animal model of thoracic IORT, the clinical study demonstrated major toxicity with respiratory and esophageal morbidity. The therapeutic usefulness of thoracic IORT in the management of lung cancer must be questioned in view of this small but consistent series of patients. Further carefully designed clinical studies using lower doses of IORT are needed.

Adult↗

Pathological tissue changes following intraoperative radiotherapy.

Ninety patients with a variety of advanced-stage malignancies were treated with surgical resection, when feasible, and with intraoperative radiotherapy. Certain patients received additional external beam radiotherapy. During clinical follow-up, 45 patients died. Twenty-two patients (49% of deaths) underwent detailed autopsies between 1 and 18 months after treatment, with special attention directed towards assessing radiation damage to various tissues. Histological changes related to radiation were generally manifested as fibrosis. Mild fibrotic changes in retroperitoneal soft tissues and mild hypocellularity in vertebral bone marrow were consistently present in patients treated for pancreatic carcinoma, gastric carcinoma, and retroperitoneal or pelvic sarcomas. Fibrosis of the soft tissues of the porta hepatis without narrowing of the bile duct was present in patients treated for pancreatic or gastric cancer. perineural fibrosis was present in retroperitoneal and pelvic nerve trunks in patients treated for abdominal or pelvic sarcomas and in patients treated for unresectable carcinoma of the pancreas. Significant radiation-related changes were generally not observed in major blood vessels, intestine, or ureter. Intact irradiated primary tumors consistently displayed necrosis.

Autopsy↗