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Biomedical subjects

J W Mulder

Publications and source records attributed to J W Mulder.

At least 55 records · Page 3Linked to original sources
PubMed1999

Rapid quantification of delavirdine, a novel non-nucleoside reverse transcriptase inhibitor, in human plasma using isocratic reversed-phase high-performance liquid chromatography with fluorescence detection.

Delavirdine is a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1-infected patients. A simple and rapid high-performance liquid chromatographic method for the quantification of delavirdine in human plasma suitable for drug monitoring in patients is described. Sample pretreatment consists of protein precipitation with acetonitrile and subsequent evaporation of the extract to concentrate the analyte. The drug is separated from endogenous compounds by isocratic reversed-phase, high-performance liquid chromatography coupled with fluorescence detection. The optimal excitation and emission wavelengths are 300 and 425 nm, respectively. The method has been validated over the range of 50-50 000 ng/ml using only 200 microl of plasma samples. The assay is linear over this concentration range as indicated by the F-test for lack of fit. Within- and between-day precisions are less than 4.4% for all quality control samples. The lower limit of quanititation is 50 ng/ml. Recovery of delavirdine from human plasma is 93.8%. Delavirdine is stable under various conditions, for example 1 h at 60 degrees C and one week at 4 degrees C. This validated assay is suited for use in pharmacokinetic studies with delavirdine and can readily be implemented in the setting of a hospital laboratory for the monitoring of delavirdine concentrations.

Anti-HIV Agents↗
PubMed1999

Paclitaxel in the treatment of human immunodeficiency virus 1-associated Kaposi's sarcoma--drug-drug interactions with protease inhibitors and a nonnucleoside reverse transcriptase inhibitor: a case report study.

PURPOSE: To describe the pharmacokinetics of paclitaxel and to investigate the interaction potential with protease inhibitors (indinavir, ritonavir, saquinavir) and the nonnucleoside reverse transcriptase inhibitor nevirapine, for which strong theoretical indications for clinically relevant drug interactions exist. METHODS: The 24-h plasma pharmacokinetics of paclitaxel (Taxol, given at 100 mg/m2 by 3-h intravenous infusion) and concomitantly infused antiretroviral drugs were determined in a human immunodeficiency virus 1 (HIV-1)-infected male patient with refractory Kaposi's sarcoma (KS) during high-activity antiretroviral therapy and after discontinuation of this regimen. The plasma pharmacokinetics of paclitaxel, indinavir, ritonavir, saquinavir, and nevirapine were closely monitored. Since all these drugs are extensively metabolized via the cytochrome P450 enzyme system and are substrates for the multidrug transporter P-glycoprotein, investigation of drug-drug interactions was considered important. RESULTS: In this case report study the pharmacokinetics of paclitaxel given concomitantly with various antiretroviral drugs were comparable with those of historical controls who had been treated with single-agent paclitaxel. The pharmacokinetics of indinavir, ritonavir, saquinavir, and nevirapine were also not statistically significantly different from those recorded for historical controls. Paclitaxel was well tolerated and resulted in a significant clinical response in this patient. CONCLUSION: Dose adjustments of paclitaxel, indinavir, ritonavir, saquinavir, or nevirapine are apparently not needed if HIV-1-associated KS is treated with paclitaxel at a dose of 100 mg/m2 as shown in the present case. It is stressed, however, that controlled studies are necessary to substantiate these preliminary case report findings.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Efficacy and safety of combination therapy with delavirdine and zidovudine: a European/Australian phase II trial.

The objective of the study was to investigate the safety and antiviral effect of three delavirdine dose regimens or placebo in combination with zidovudine in patients who were already taking zidovudine. Eighty-nine symptomatic HIV-1 seropositive individuals with CD4 cell counts between 50 and 350 cells/microl were included in this trial The influence of combination therapy on viral susceptibility to both zidovudine and delavirdine was investigated. Death or the occurrence, or re-occurrence of an AIDS-defining illness was considered as a clinical endpoint. The addition of delavirdine to the antiretroviral treatment regimen resulted in a significant, but transient, reduction in virus load, as determined by quantitative RNA measurements. CD4+ cell count did not change significantly. Susceptibility to zidovudine remained unchanged after 12 weeks of combination therapy, while 70% of the patients demonstrated a substantial decrease (> 10-fold) in sensitivity to delavirdine. Two patients suffered from an AIDS-defining disease during the study. No deaths occurred. Generally, the drug appeared to be safe. Skin rash was the most frequently observed adverse event (52%). In most patients the rash either resolved spontaneously or was treated successfully with a short course of antihistamines. The definite place of the compound in the management of HIV disease, in particular when given in combination with other antiretroviral agents, remains to be further explored.

Anti-HIV Agents↗
PubMed1999

Accuracy of ultrasonography and magnetic resonance imaging in detecting failure of breast implants filled with silicone gel.

We prospectively studied the accuracy of magnetic resonance imaging (MRI) and ultrasonography (US) for preoperative detection of rupture in 35 single-lumen implants filled with silicone gel in 18 patients. The positive predictive value of US for rupture of an implant was 70% and the negative predictive value 64%. Sensitivity and specificity were 44% and 87%, respectively. Accuracy, defined as the total true positive and true negative values divided by the total number of implants studied was 66%. The positive predictive value of MRI was 100% and the negative predictive value 90%. The corresponding sensitivity and specificity were 88% and 100% and the accuracy 94%. MRI offers significantly better diagnostic sensitivity (p = 0.02) and accuracy (p = 0.004), and should be regarded as the "gold standard" in the evaluation of rupture of breast implants filled with silicone gel. When MRI is not readily available, US is an acceptable alternative.

Adult↗
PubMed1999

Augmentation mammaplasty: the story before the silicone bag prosthesis.

Czerny from Heidelberg is generally accepted to have performed the first augmentation mammaplasty in 1895. Since then, a variety of nonsilicone materials have been injected or implanted to augment or to reconstruct the hypoplastic female breast, including autologous tissues, intramammary- or submammary-injected alloplastic materials, and preformed alloplastic materials other than silicone. For various reasons outlined in this review, none was fully acceptable. The introduction of the medical-grade silicone bag prosthesis in the early 1960s improved the results of mammary augmentation dramatically and reduced the incidence of fibrous contracture and implant extrusion. Other methods of breast augmentation became obsolete.

Breast Implants↗
PubMed1999

Exceptional presenting conditions and outcome of augmentation mammaplasty in male-to-female transsexuals.

Driven by a persistent and unchangeable need to undo the discrepancy between reality of the body and gender of the mind, most male-to-female transsexuals seek physical feminization through hormonal and surgical treatment. The authors report some rare presenting conditions and exceptional results of augmentation mammaplasty in 11 male-to-female transsexuals treated between January 1979 and January 1998, as well as describe how to treat these conditions. In patients in whom gynecomastia was treated previously, the remaining subcutaneous fatty tissue may be insufficient to cover the implants safely, and subpectoral implantation should be considered. Augmentation after unilateral correction of gynecomastia requires different sizes of implants. Although exceptional in male-to-female transsexuals, mastopexy is the treatment of choice to correct any mammary ptosis, but the patient may request augmentation mammaplasty to fill out the breasts. Previous stacking mammaplasty may have been performed subglandularly, subpectorally, or both. Stacking may not have been noticed prior to corrective surgery. Extrusion of the implant may be associated with avascular necrosis or infection, but also with the use of high concentrations of steroid placed within the lumen of fluid-filled implants. The correction involves removal of the implant, with skin graft or flap reconstruction of the affected area. Replacement of the implant may have to be delayed. Symmastia results from overzealous medial dissection coupled with overaugmentation. Combined restoration of the presternal subcutaneous integrity, and medial closure of the pocket by subcutaneous approach only, leads to satisfactory reconstruction of the presternal median cleavage. Galactorrhea may be the result of hyperprolactemia but is more often caused by stimulation of the intercostal nerve by the implants.

Adolescent↗
PubMed1999

Augmentation mammaplasty in male-to-female transsexuals.

Hormonal therapy and gender-confirming surgery are the treatments of choice in appropriately selected male-to-female transsexuals. Penectomy and vaginoplasty are the paramount surgical requests of the male transsexual, but breast enlargement greatly increases subjective feelings of femininity. There are only limited reports on augmentation mammaplasty in male transsexuals, and hardly any attention has been paid to the differences between the female mammary anatomy and its male counterpart. The basic anatomic and surgical considerations of augmentation mammaplasty for 201 male-to-female transsexuals who were operated on from 1979 to 1997 are reviewed and discussed. They include the differences between male and female anatomy and how to feminize the male chest, the results of hormonal therapy and the proper timing of surgery, the choice of implant size and surgical approach, the results that may be expected after surgery, and the implications of all mentioned on the long-term outcome and follow-up after augmentation mammaplasty. Because the referring doctor may not check on the breasts or may not be trained to examine augmented breasts for pathologic conditions, the mammaplastic surgeon has an obligation to ensure the proper follow-up of these patients.

Adult↗
PubMed1999

Pierre Robin syndrome: mandibular growth during the first year of life.

Micrognathia and glossoptosis may cause severe respiratory and feeding difficulties in newborns with Pierre Robin syndrome. The growth of the mandible is alleged to more or less "catch up" during the first year of life. We could not objectify such a catch-up growth using the noninvasive and harmless measurement of the jaw index. The jaw index is defined as alveolar overjet x maxillary arch/mandibular arch. The alveolar overjet is the frontodorsal distance between the most anterior points of the upper and lower alveolar arches, whereas the maxillary arch is measured from the left tragus to the right tragus via the subnasal point, and the mandibular arch is measured from the left to the right tragus via the pogonion point. The growth of the mandible in 7 Pierre Robin patients was found to be proportionately similar to that observed in healthy control subjects age 0 months (N = 100), 6 months (N = 42), and 1 year (N = 32).

Case-Control Studies↗
PubMed1998

Comparison of the plasma pharmacokinetics and renal clearance of didanosine during once and twice daily dosing in HIV-1 infected individuals.

OBJECTIVE: To compare the plasma pharmacokinetics of didanosine during once daily (qd) and twice daily (bid) dosing. DESIGN: Open-label, randomized, cross-over study. METHODS: HIV-1 infected patients who used didanosine were randomized to either a qd or a bid dosing regimen of didanosine. The total daily dose of didanosine was identical in both regimens. Seven days after the start of the study, the pharmacokinetic profile of didanosine in plasma and urine was assessed during an 8-h period. The next day, the patient was switched to the opposite dosing regimen, and after another 7 days, the study was concluded by again assessing the plasma and urine pharmacokinetics of didanosine during 8 h. RESULTS: A total of 19 patients completed the study. The pharmacokinetics of didanosine in plasma (with maximum plasma concentration adjusted for dose) and urine were not significantly different in the qd and bid dosing regimen (P > 0.28 for all parameters). CONCLUSION: We conclude that qd dosing of didanosine leads to a similar exposure in plasma as bid dosing (using the same total daily dose). Since qd dosing may lead to improved compliance of patients to regimens containing didanosine, these results provide a rationale for prescribing didanosine in a qd regimen, and is reassuring when we realize that the drug is being administered in a qd dosing regimen on a large scale in clinical practice.

Adult↗
PubMed1998

Simultaneous quantitative determination of the HIV protease inhibitors amprenavir, indinavir, nelfinavir, ritonavir and saquinavir in human plasma by ion-pair high-performance liquid chromatography with ultraviolet detection.

A reversed-phase high-performance liquid chromatographic assay for the simultaneous quantitative determination of five HIV protease inhibitors (i.e. amprenavir, indinavir, nelfinavir, ritonavir, and saquinavir) in human plasma is described. Sample pretreatment consisted of solid-phase extraction prior to ion-pair, reversed-phase high-performance liquid chromatography with ultraviolet detection at 210 nm (amprenavir, indinavir and nelfinavir) and 239 nm (saquinavir and ritonavir). For amprenavir, indinavir and saquinavir the method has been validated over the range of 25 ng/ml to 25 microg/ml using a 0.6 ml sample volume. For nelfinavir and ritonavir the method has been validated over the range of 50 ng/ml to 25 microg/ml. The method proved to be accurate, with an average accuracy at four concentrations ranging from 90.6 to 109.2%, and precise, with the within-day and between-day precision ranging from 1.8 to 6.7%, and 0.7 to 7.6%, respectively. The protease inhibitors which can be quantified by using this assay proved to be stable under various conditions. This assay can readily be used in a hospital laboratory for the routine monitoring of plasma concentrations of these protease inhibitors.

Anti-HIV Agents↗
PubMed1998

Rapid determination of nevirapine in human plasma by ion-pair reversed-phase high-performance liquid chromatography with ultraviolet detection.

Nevirapine is a non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1-infected patients. A simple and rapid high-performance liquid chromatographic method for the quantification of nevirapine in human plasma is described. Sample pretreatment consists of protein precipitation with acetonitrile. The analyte is separated from endogenous compounds by isocratic reversed-phase, ion-pair, high-performance liquid chromatography with ultraviolet detection at 282 nm. The method has been validated over the range of 52-10400 ng/ml using 250 microl of plasma. The assay was linear over this concentration range. Within- and between-day precisions were less than 4.5% for all quality control samples. The lower limit of quantitation was 52 ng/ml. Recovery of nevirapine from human plasma was 94.5%. This validated assay is suited for use in pharmacokinetic studies with nevirapine and can readily be used in a hospital laboratory for the monitoring of nevirapine concentrations.

Anti-HIV Agents↗
PubMed1998

Quantitative determination of (-)-2'-deoxy-3'-thiacytidine (lamivudine) in human plasma, saliva and cerebrospinal fluid by high-performance liquid chromatography with ultraviolet detection.

A high-performance liquid chromatographic method for the quantitative determination of the HIV reverse transcriptase inhibitor lamivudine ((-)-2'-deoxy-3'-thiacytidine, 3TC, Epivir) in human plasma, saliva and cerebrospinal fluid is described. Lamivudine was extracted from samples using silica extraction columns prior to reversed-phase high-performance liquid chromatography with ultraviolet detection at 270 nm. The method has been validated over the range of 10 (lower limit of quantitation) to 5000 ng/ml using a 0.5-ml sample volume. Between-day and within-day precisions ranged from 3.5 to 9.0%. The assay has been used for the quantitative analysis of lamivudine in plasma and cerebrospinal fluid of HIV-1 infected patients.

Anti-HIV Agents↗
PubMed1998

The effect of plasma drug concentrations on HIV-1 clearance rate during quadruple drug therapy.

OBJECTIVE: To investigate the relationship between exposure to antiretroviral drugs and the initial decline of plasma HIV-1 RNA. DESIGN: Open-label study in antiretroviral-naive HIV-1 infected patients using a quadruple drug regimen [nelfinavir (NFV), saquinavir (SQV), stavudine, and lamivudine]. METHODS: The elimination rate constant (k) for HIV-1 clearance was calculated during the first 2 weeks of treatment in 29 patients. Exposure to NFV and SQV was quantified on each study visit. Observed NFV and SQV concentrations were related to those expected in a reference population and a concentration ratio was calculated. The median concentration ratios for NFV and SQV, the baseline CD4+ lymphocyte count and baseline log10 HIV-1 RNA were correlated with k. RESULTS: A significant positive correlation was observed between k and the median NFV (P = 0.001) or SQV concentration ratio (P = 0.016) in univariate analysis. In multivariate analyses, the median NFV concentration ratio remained significantly correlated with k. CONCLUSIONS: The variation in the rate of decline of plasma HIV-1 RNA between patients after the initiation of a quadruple drug regimen could be explained by differences in exposure to NFV or SQV. Determination of k could be used to optimise further antiretroviral drug therapy and may be a first tool to assess antiretroviral activities of new or increasing doses of drugs administered in combination regimens. Furthermore, our data suggest that exposure to antiretroviral drugs should be incorporated in mathematical models to describe HIV-1 dynamics in more detail.

Anti-HIV Agents↗
PubMed1998

Maintenance therapy after quadruple induction therapy in HIV-1 infected individuals: Amsterdam Duration of Antiretroviral Medication (ADAM) study.

BACKGROUND: Highly active antiretroviral therapy (HAART) has led to health benefits for patients infected with HIV-1. However, long-term use of multidrug regimens is difficult to sustain. Simplifying antiretroviral treatment regimens would increase patients' adherence and minimise toxicity. We investigated the feasibility of a strategy of induction therapy followed by maintenance therapy with HAART in a randomised open-label study. METHODS: From March, 1997, we enrolled patients infected with HIV-1 with at least 200 CD4 cells/microL, at least 1000 HIV-1 RNA copies/mL in plasma, and no previous exposure to antiretroviral drugs. After 26 weeks of induction therapy (stavudine, lamivudine, saquinavir, and nelfinavir) patients were randomly allocated maintenance therapy (either stavudine and nelfinavir or saquinivir and nelfinavir) or prolonged induction therapy (if the plasma HIV-1 RNA concentration at weeks 24 and 25 was <50 copies/mL). FINDINGS: In February, 1998, we discontinued randomisation after an interim analysis. 62 patients had been enrolled. 39 (91%) of the 43 patients who were followed up for at least 26 weeks had an undetectable plasma HIV-1 RNA concentration at week 16. At week 26, 31 patients were randomly allocated treatment. Of these patients 25 had a total follow-up of at least 36 weeks. At week 36, a higher proportion of patients on maintenance therapy (nine [64%] of 14) had a detectable HIV-1 RNA than patients on prolonged induction therapy (one [9%] of 11, p=0.01). The initial virion-clearance rate during induction therapy was higher in five patients on maintenance therapy with a sustained undetectable plasma HIV-1 RNA concentration than in nine patients with recurrence of a detectable plasma HIV-1 RNA concentration at week 36 (0.35 vs 0.19 per day, respectively; p=0.0008). INTERPRETATION: The induction regimen provided a rapid suppression of viral replication to below 50 copies/mL. However, suppression was not sustained in a considerable number of patients who went onto maintenance therapy. It is currently inadvisable to continue attempts at moving from induction to maintenance therapy in day-to-day practice.

Adult↗
PubMed1998

High-performance liquid chromatographic determination of ritonavir in human plasma, cerebrospinal fluid and saliva.

A simple, ion-pair high-performance liquid chromatographic method has been developed and validated for the quantitative determination of the HIV protease inhibitor ritonavir in human plasma, cerebrospinal fluid and saliva. Sample pretreatment consisted of precipitation of proteins with acetonitrile prior to high-performance liquid chromatography with ultraviolet detection at 239 nm. The method has been validated over the range of 50 ng/ml to 50 microg/ml with use of 100-microl volumes of sample. The currently described assay has been used successfully for the analysis of ritonavir in plasma, cerebrospinal fluid and saliva in HIV-1 infected patients.

Acquired Immunodeficiency Syndrome↗