Search PubMed⌕ Search

Biomedical subjects

J W Mulder

Publications and source records attributed to J W Mulder.

At least 73 records · Page 4Linked to original sources

CD44 splice variants as prognostic markers in colorectal cancer.

BACKGROUND: Splice variants of CD44 play a causal role in the metastatic spread of pancreatic carcinoma in the rat. In previous studies we have shown that homologues of these CD44 isoforms (CD44v6) are overexpressed during colorectal tumorigenesis in man and that CD44v6 overexpression is associated with an unfavorable prognosis in this disease. In the present study we have assessed the prognostic significance of CD44 variants containing exon v5. In addition, we have used a panel of different antibodies against CD44v6 and applied a combined scoring system to improve its value as prognosticator. METHODS: Expression of CD44 variants was studied by immunohistochemistry on frozen tissue sections, and the prognostic value of the CD44 variant expression was assessed using univariate and multivariate analysis. RESULTS: Our studies show that expression of CD44v6, but not CD44v5, has significant prognostic value. Analysis of CD44v6 expression by means of a combined scoring system, on the basis of a panel of three different monoclonal antibodies (mAbs), makes CD44v6 a highly significant prognostic marker that is independent of Dukes stage, tumor grade, or tumor localization. CONCLUSION: Assessment of CD44v6 expression by a combination of mAbs yields an independent prognosticator that may be of value in identifying patients with a high propensity to develop distant metastasis.

Adult↗

Stimulation of cartilage differentiation by osteogenic protein-1 in cultures of human perichondrium.

Exposure of progenitor cells with chondrogenic potential to recombinant human osteogenic protein-1 [rhOP-1, or bone morphogenetic protein-7 (BMP-7] may be of therapeutic interest in the regeneration of articular cartilage. Therefore, in this study, we examined the influence of rhOP-1 on cartilage formation by human perichondrium tissue containing progenitor cells with chondrogenic potential in vitro. Fragments of outer ear perichondrium tissue were embedded in clotting autologous blood to which rhOP-1 had been added or not (controls), and the resulting explant was cultured for 3 weeks without further addition of rhOP-1. Cartilage formation was monitored biochemically by measuring [&sup35;S]sulfate incorporation into proteoglycans and histologically by monitoring the presence of metachromatic matrix with cells in nests. The presence of rhOP-1 in the explant at the beginning of culture stimulated [&sup35;S]sulfate incorporation into proteoglycans in a dose-dependent manner after 3 weeks of culture. Maximal stimulation was reached at 40 microgram/ml. Histology revealed that explants treated with 20-200 microgram/ml rhOP-1, but not untreated control explants, contained areas of metachromatic-staining matrix with chondrocytes in cell nests. These results suggest that rhOP-1 stimulates differentiation of cartilage from perichondrium tissue. The direct actions of rhOP-1 on perichondrium cells to stimulate chondrocytic differentiation and production of cartilage matrix in vitro provide a cellular mechanism for the induction of cartilage formation by rhOP-1 in vivo. Thus, rhOP-1 may promote early steps in the cascade of events leading to cartilage formation. Therefore, rhOP-1 could be an interesting factor for regeneration of cartilage in articular cartilage defects.

Adolescent↗

The lip index: an anthropometric tool to evaluate objectively the result of the Abbe flap procedure.

To evaluate objectively the outcome of the Abbe flap procedure, an anthropometric ratio--the lip index--is introduced. The lip index is the ratio of the labiale superius-tragion to the labiale inferius-tragion. It represents the protrusion of the upper lip in relation to the lower lip. It has been assessed in preoperative and postoperative photographs of 19 patients who underwent an Abbe flap procedure. The values were compared with the values found in noncleft patients. In all 19 patients, postoperative values were found to have normalized. This study indicates that the lips are in better harmony postoperatively than they were preoperatively.

Adolescent↗

Imaging signs and radiologists' jargon of ruptured breast implants.

Silicone gel leakage problems are central to the furor over the complications alleged to be caused by breast implants. Because clinical examination may not reveal confirmatory signs of gel bleed or rupture, radiologists are often requested by plastic surgeons to evaluate the integrity of the implant's envelope. The findings of the various imaging investigations are reported in terms such as "teardrop," "linguini," and "snowstorm." To interpret the radiologist's report correctly, the plastic surgeon should be familiar with these terms and the findings they represent. In this article, we present an explanation of the radiologists' vocabulary in these matters, as well as an indication as to the significance of the various signs.

Breast↗

Co-trimoxazole and stavudine interference in a high-performance liquid chromatographic analysis for didanosine in human plasma.

Recently, the authors were confronted with interference of stavudine and co-trimoxazole when analyzing the antiretroviral drug didanosine (ddI) in plasma of HIV-1-infected patients using reverse-phase high-performance liquid chromatography with ultraviolet detection. After increasing the percentage of methanol in the mobile phase from 4% to 8% vol/vol and after decreasing the pH of the mobile phase from 6.8 to 5.8, the authors were able to separate didanosine from stavudine and co-trimoxazole (both are frequently used drugs in combination with didanosine). Subsequently, the adapted bioanalytic methodology was validated, and validation results showed that this new methodology can be used for the quantitative determination of didanosine in human plasma. This observation makes clear that combination therapy for human immunodeficiency virus with multiple (often chemically related) drugs has the potential of unexpectedly complicating bioanalytic analyses because therapeutic strategies may change rapidly after publication of a bioanalytic methodology. Thus, it is evident that the investigation of interference of potentially coadministered drugs should be a standard procedure during the development of any bioanalytical methodology in any laboratory.

Anti-HIV Agents↗

Hepatitis during chloroguanide prophylaxis.

OBJECTIVE: To describe a case of severe hepatitis that we attribute to the use of chloroguanide. CASE SUMMARY: A patient was admitted with fever and jaundice. This man had recently returned from Indonesia and was still using chloroguanide 200 mg once daily for 6 weeks. Evaluation of the liver function test results was consistent with cholestatic liver disease (alkaline phosphatase 158 U/L, aspartate aminotransferase 33 U/L, alanine aminotransferase 58 U/L increasing up to 183 U/L, gamma-glutamyl transferase 96 U/L). This condition was thought to be caused by chloroguanide. A biopsy of the liver indicated drug-induced hepatitis. DISCUSSION: To our knowledge, this is the first report in the literature of cholestatic hepatitis associated with chloroguanide prophylaxis. In our patient, chloroguanide-induced hepatotoxicity can be considered as a combined allergic and idiosyncratic manifestation. CONCLUSIONS: This case shows that it is possible to develop drug-induced hepatitis with considerable morbidity while taking chloroguanide prophylaxis.

Antimalarials↗

Low plasma concentrations of indinavir are related to virological treatment failure in HIV-1-infected patients on indinavir-containing triple therapy.

All human immunodeficiency virus type 1 (HIV-1)-infected patients who started to use indinavir (800 mg three times a day) as part of their triple drug regimen were included in a study to determine the importance of low plasma concentrations of indinavir as a cause of virological treatment failure. The indinavir concentration and a number of patient characteristics at baseline were tested as risk factors for virological treatment failure (defined as a viral load above 200 copies/ml after 24 weeks of treatment) in univariate and multivariate analyses; 65 patients were included. Virological treatment failure occurred in 36.9% of the patients. Multivariate analysis showed that a low plasma concentration of indinavir (odds ratio 0.1), a high viral load at baseline (odds ratio 2.6) and pretreatment with another protease inhibitor (odds ratio 10.0) were independent factors related to virological treatment failure. Monitoring of indinavir plasma concentrations may be an important tool for the optimization of triple drug combination therapy.

Acquired Immunodeficiency Syndrome↗

Determination of saquinavir in human plasma, saliva, and cerebrospinal fluid by ion-pair high-performance liquid chromatography with ultraviolet detection.

A high-performance liquid chromatographic method for the determination of the HIV protease inhibitor saquinavir in human plasma, saliva, and cerebrospinal fluid is described. Saquinavir was extracted from samples using C2 extraction columns prior to ion-pair, reversed-phase high-performance liquid chromatography with ultraviolet detection at 239 nm. The method has been validated over the range of 2.5-4000 ng/ml using a 0.6-ml sample volume. This assay has been used for the analysis of saquinavir in plasma and saliva of HIV-1-infected patients.

Anti-HIV Agents↗

Penetration of 3'-amino-3'-deoxythymidine, a cytotoxic metabolite of zidovudine, into the cerebrospinal fluid of HIV-1-infected patients.

The penetration of 3'-amino-3'-deoxythymidine (AMT) into the cerebrospinal fluid (CSF) of HIV-1-infected patients has been investigated. In 23 patients who used zidovudine (ZDV) chronically, CSF and plasma samples were assayed for AMT and ZDV. The influences of time between ZDV oral administration and lumbar puncture, of ZDV dose, and of the medical indication for lumbar puncture based on the concentration of AMT in CSF and on the CSF-plasma concentration ratio were investigated. AMT can be detected in the CSF after oral administration of ZDV; concentrations of AMT in CSF ranged from 0.75 to 4.8 ng/ml (median, 1.7 ng/ml). The median CSF-plasma concentration ratio was 1, and equaled that for ZDV. CSF and plasma concentrations of AMT were approximately threefold higher in patients with cerebral toxoplasmosis; the CSF-plasma concentration ratio remained equal to unity in these cases. This phenomenon might be caused by a pharmacokinetic interaction between AMT and pyrimethamine, sulfadiazine, folinic acid, or a combination of these. The clinical relevance of AMT, especially the possibility of decreased efficacy of ZDV, throughout the body and in the central nervous system, and the involvement of this metabolite in ZDV-induced myelosuppression, remains to be established.

Administration, Oral↗

Restoration of elbow flexion 16 years after brachial plexus root avulsion.

To restore elbow flexion in brachial plexus lesions or cervical root avulsions, surgical nerve reconstruction can be attempted after approximately 6 months. If the reconstruction is not successful or was not performed, tendon transfer may improve the function of a paralysed limb. The selection of the muscle for transfer can be influenced by strengthening potentially available muscles by a myo-feedback method.

Adult↗

Bone grafting the piriform aperture deformity in isolated cleft lip patients: indication, technique, and results.

PURPOSE: This study was undertaken to determine the effect of a bone graft in the piriform aperture on the nasal deformity and orthodontic treatment of the cleft side teeth in isolated cleft lip patients. PATIENTS AND METHODS: All primary cleft lip repair was done 3 months after birth. Nine patients, four female and five male, with a mean age of 12.5 years (range, 8.2 to 24.8 years) and with a repaired cleft lip, were bone grafted between 1992 and 1996. The mean postoperative period was 2 years (range, 1 to 4 years). An iliac crest bone graft was placed in the piriform aperture deformity on the side of the cleft lip. The improvement in the nasal symmetry and angulation of the cleft side teeth were evaluated. The eight growing cleft lip patients (mean age, 11 years; range, 9 to 13 years) were compared with a control group of eight healthy growing children (mean age, 11 years; range, 9 to 13 years). The improvement of nasal symmetry was measured by the formula of the lobule portion of the columella index preoperatively and postoperatively. RESULTS: The mean lobule portion of the columella index preoperatively was 41.8% (SD, 4.4%; SE of Mean, 1.5%) and postoperatively was 44.2% (SD, 4.9%; SE of Mean, 1.6%) (P > .006, t-test for paired samples). The angulation of the cleft side teeth was improved by orthodontic treatment. CONCLUSION: Bone grafting the piriform aperture deformity results in a stable result and improves nasal symmetry and the angulation of the cleft side teeth.

Adolescent↗

Clinical pharmacology of HIV protease inhibitors: focus on saquinavir, indinavir, and ritonavir.

In this review the clinical pharmacology of HIV protease inhibitors, a new class of antiretroviral drugs, is discussed. After considering HIV protease function and structure, the development of inhibitors of HIV protease is presented. Three protease inhibitors are reviewed in more detail: saquinavir, indinavir, and ritonavir. Clinical trial results with these agents are evaluated. Furthermore, adverse effects, resistance, dosage and administration, clinical pharmacokinetics, pharmacokinetic-pharmacodynamic relationships, and drug interactions are discussed.

Acquired Immunodeficiency Syndrome↗

p53 and CD44 as clinical markers of tumour progression in colorectal carcinogenesis.

Recent advances in molecular genetics have importantly improved our understanding of the development of colorectal cancer. The present review gives an overview of the clinical value of the tumour-suppressor gene, p53, and the CD44 cell adhesion molecule in colorectal cancer and the pitfalls encountered in the immunohistochemical detection of these proteins. Immunohistochemistry potentially forms a procedure applicable for routine diagnosis and prognostication. Therefore, p53 expression and the independent prognostic importance of CD44v6 expression is given particular emphasis, and other molecular events underlying colorectal carcinogenesis are only mentioned briefly.

Adenocarcinoma↗

Life span of silicone gel-filled mammary prostheses.

The discussion on possible side effects of implanted silicone has resulted in a growing number of patients inquiring whether or not their mammary prostheses are intact and when failure of the prostheses is to be expected. Between November 1988 and May 1995, 182 patients had their silicone mammary prostheses replaced, repositioned, or removed one to three times. Capsular contraction, dislocation, pain paresthesia, and/or suspected rupture were common indications for surgery. To try and be able to provide an indication as to the correlation of implant age and integrity, we recorded the status of all 426 prostheses observed during secondary surgery. In this selected group of patients, approximately 50 percent of the mammary prostheses with an implant age of 7 to 10 years showed gel bleed or rupture. Applying the survival Kaplan-Meier curve, 50 percent of implants may be expected to bleed or be ruptured at the age of 15 years. Rupture was observed more frequently than gel bleed. It seems that there is no chronologic relation between gel bleed and rupture.

Adult↗

Major residual deformities in cleft patients: a new anthropometric approach.

OBJECTIVE: A new method based on anthropometric ratios and inclinations was evaluated to confirm or reject whether residual deformities in cleft patients' faces differ significantly from faces without previous clefts. DESIGN, SETTING, AND PATIENTS: From a retrospective, a selective review of our clinical files, seven measurements were made on 156 photographs of the faces of 52 patients aged 19 to 25 years. There ratios and two inclination angles were recorded for each patient. RESULTS: The primary hypothesis could be confirmed: the anthropometric ratios and angles used to express major residual deformities in cleft lip and nose patients differ significantly from normal values. CONCLUSION: This new method allows for objective measurement and evaluation of both the stigmata and the outcome of their treatment.

Adult↗

The jaw index: new guide defining micrognathia in newborns.

OBJECTIVE: Newborns with glossoptosis due to micrognathia can suffer from life-threatening respiratory distress and severe feeding difficulties. These characteristic features are found in newborns with Pierre Robin sequence. In the relevant literature, no concensus concerning diagnosis for these children can be found. A guide defining micrognathia can be helpful in the diagnosis of glossoptosis and possible airway obstruction. METHOD: The jaw index is obtained in newborns by measuring three facial dimensions. In a series of 100 healthy neonates the standard measures were defined. RESULTS: The average jaw index in children with Pierre Robin sequence differs significantly from the reference group and was found to be over 3.6 times the normal value. CONCLUSIONS: Micrognathia can be defined with the jaw index.

Airway Obstruction↗

Clinically relevant drug interactions with antiretroviral agents.

With the advent of the human immunodeficiency virus (HIV) protease inhibitors and the non-nucleoside reverse transcriptase inhibitors, the importance of drug-drug interactions with antiretroviral agents is becoming increasingly recognized. Every clinician involved in the care of HIV-infected persons should have a broad knowledge of these drug-drug interactions and their underlying mechanisms. This paper will review currently known clinically relevant interactions with antiretroviral agents reported thus far. Alternative strategies will be proposed where possible, in order to improve patient safety and the therapeutic efficacy of the antiretroviral agents. It must be emphasized, however, that in many cases these proposals are not backed up by authoritative clinical consensus panels and that clinical experience with many of these combinations is limited.

Anti-HIV Agents↗