Virtual endoscopy of the nose and paranasal sinuses

The purpose of this study was to evaluate the applicability of virtual endoscopy (VE) in the region of the nose and paranasal sinuses on the basis of volume-rendered spiral CT data. Forty-five patients underwent a low-dose spiral CT of the sinuses. The data were transferred to a workstation running software for volume rendering (EasyVision, Philips Medical Systems, Eindhoven, The Netherlands). Six orthogonal views of the maxillary sinuses and the nasopharynx and a fly-through movie of the nose were calculated. Two radiologists evaluated the coronal reconstructions and virtual endoscopy with respect to detectability of pathology using a checklist comprising 10 points. In 30 patients who underwent subsequent endoscopic surgery, surgeons were asked to rank the degree of assistance of the preoperative virtual endoscopy. In general, virtual endoscopy was possible in all 45 patients. The mean time required for path definition and movie calculation for virtual endoscopy were 8 ( ± 2) min and 3 ( ± 1) min, respectively. Overall, more anatomical details were depicted on coronal reconstructions; however, a high degree of similarity between virtual endoscopy and the intraoperative impression was reported by the surgeons. We conclude that virtual endoscopy of the nose and paranasal sinuses may develop into a standard means to guide surgeons during endoscopic interventions. Received 17 September 1997; Revision received 23 December 1997; Accepted 29 December 1997     

Cytokine responses to stimulation of whole blood from patients with Buruli ulcer disease in Ghana

Buruli ulcer disease (BUD), caused by Mycobacterium ulcerans, follows an indolent course of initial progression to ulceration accompanied by extensive tissue damage. It has been suggested that healing disease stages are accompanied by a protective immune response. We hypothesized that interleukin-4 (IL-4)- or IL-10-induced downregulation of Th-1 responses plays a key role in the progression of early BUD and that healing is accompanied by an augmented Th-1 response. Gamma interferon (IFN-gamma), IL-4, and IL-10 responses were measured after in vitro stimulation with phytohemagglutinin (PHA) and tuberculin purified protein derivative (PPD) of whole blood from 39 (23 early- and 16 late-stage) BUD patients and 39 healthy control subjects in Ghana. Additionally, 30 patients with active or treated tuberculosis (TB) serving as PPD-responsive positive controls were studied. Early-stage BUD patients produced significantly lower levels of IFN and IFN-gamma/IL-4 ratios compared to late-stage BUD patients after PHA stimulation. Compared to that of controls, IFN-gamma production after tuberculin stimulation was significantly higher in late-stage but not in early-stage BUD patients (P=0.009). IL-10 and IL-4 levels did not differ between BUD patients and controls, although active TB patients had significantly higher IL-10 production levels than did treated TB patients. Multivariate analysis showed no confounding factors. In conclusion, Th-1 down regulation in early BUD appears to reverse in later stages of BUD, although an association with IL-10 or IL-4 production does not emerge from our data. Here we show differences in Th-1-type cytokine production between early- and late-stage BUD that might reflect an improved immune defense over time.     

Staphylococcus aureus pancarditis complicated by a left ventricular pseudoaneurysm

Acute septic pancarditis is a life threatening but fortunately rare condition. We report a case of this condition in a young 20-year-old female patient with an early complication of mitral valve destruction and a late complication of a left ventricular pseudoaneurysm formation.     

Light propagation in dentin: influence of microstructure on anisotropy

We investigated the dependence of light propagation in human dentin on its microstructure. The main scatterers in dentin are the tubules, the shape of which can be approximated as long cylinders. We calculated the scattering of electromagnetic waves by an infinitely long cylinder and applied the results in a Monte Carlo code that simulates the light propagation in a dentin slab considering multi-scattering. The theory was compared with goniometric measurements. A pronounced anisotropic scattering pattern was found experimentally and theoretically. In addition, intensity peaks were measured which are shown to be caused by light diffraction by the tubules.     

Screening for illicit heroin use in patients in a heroin-assisted treatment program

The aim of this study was to investigate the use of illicit heroin among patients in a heroin-assisted treatment program. In this program, pharmaceutical-grade heroin was administered to heroin-addicted patients. Monitoring of illicit heroin use was considered important for the evaluation of this treatment program. Acetylcodeine and codeine, common adulterants of "street" heroin, were used as markers for illicit heroin. A liquid chromatography method with tandem mass spectrometric detection (LC-MS-MS) was developed, for quantitative analysis of heroin and methadone, their metabolites, and the simultaneous detection of acetylcodeine. One-hundred patients in a heroin-assisted treatment program were screened for acetylcodeine in plasma. Furthermore, patients were interviewed about illicit heroin use, and they were tested for alcohol and cocaine use. In plasma samples of 16% of the patients, acetylcodeine was detected. Overall agreement between self-report and plasma samples was 95% (kappa: 0.81). Patients who tested positive for acetylcodeine had visited the outpatients' clinics significantly less frequently than the patients who tested negative. Alcohol and cocaine use was more common in patients who tested positive for acetylcodeine. Illicit heroin use was observed in a limited percentage of patients. Overall agreement between self-report and markers of illicit heroin use was good.     

No pharmacokinetic drug-drug interaction between nevirapine and paclitaxel

We have investigated the pharmacokinetics of nevirapine and paclitaxel in a patient who used both drugs concomitantly, as there are strong theoretical indications for a potential pharmacokinetic drug-drug interaction. Plasma concentrations of nevirapine (dose: 200 mg twice daily orally) and paclitaxel (dose: 100 mg/m(2) 3-h i.v. infusion) were determined in a HIV-1-infected patient with Kaposi's sarcoma. Since both drugs are metabolized via the same cytochrome P450 isoenzymes, investigation of a drug-drug interaction was considered important. We found that the plasma concentrations of nevirapine given together with paclitaxel were similar to those given without paclitaxel. The exposures to paclitaxel (AUC(0-infinity) = 3787 h.ng/ml) and its hydroxy metabolites when co-administered with nevirapine were comparable to the mean exposure to paclitaxel and its metabolites from eight historical controls (AUC(0-infinity) = 3614 h.ng/ml) treated with the same dose. No pharmacokinetic drug-drug interaction between nevirapine and paclitaxel could be demonstrated in our HIV-1-infected patient.     

Nevirapine and efavirenz pharmacokinetics and covariate analysis in the 2NN study

OBJECTIVE: The aim of this 2NN pharmacokinetic substudy was to investigate the population pharmacokinetics of nevirapine and efavirenz. METHODS: Treatment-naive, HIV-1-infected patients received nevirapine (once or twice daily), efavirenz or a combination with lamivudine and stavudine. Blood samples were collected on day 3 and weeks 1, 2, 4, 24 and 48. Using non-linear mixed effects modelling, pharmacokinetics of nevirapine and efavirenz and factors involved in the inter-individual variability were investigated. RESULTS: Clearance of nevirapine in the induction phase (<14 days) and at steady state (>28 days) were 2.02 I/h and 2.81 I/h, respectively. Volume of distribution and absorption rate constant were 77.0 l and 1.66 h(-1), respectively. Clearance of nevirapine was lower in females (13.8%) and in patients with hepatitis B (19.5%). Patients from South America and Western countries had higher clearance of nevirapine compared with Thai and South African patients. The clearances of efavirenz in the induction phase and at steady state were 7.95 l/h and 8.82 l/h, respectively. The volume of distribution and absorption rate constant were 4181 and 0.287 h(-1), respectively. Concomitant use of nevirapine increased clearance of efavirenz (43%). Patients from Thailand had lower clearance than the rest of the population. CONCLUSIONS: The population pharmacokinetics of nevirapine and efavirenz were assessed in the 2NN trial. For both drugs, an induction phase was distinguished from the steady-state phase. Gender, hepatitis B and geographical region were involved in the variability of the pharmacokinetics of nevirapine. Region and concomitantly used nevirapine were determinants of the pharmacokinetics of efavirenz.     

Bioanalysis of HIV protease inhibitors in samples from sanctuary sites

The human immunodeficiency virus (HIV) is present in several sites inside the human body, which are hardly accessible to antiretroviral drugs, the so-called sanctuary sites. The most important sanctuary sites are cerebrospinal fluid (CSF), peripheral blood mononuclear cells (PBMCs) and seminal plasma. The determination of drug concentrations in these sanctuary sites may form an important step in treatment optimisation of HIV-infected individuals. However, bioanalysis in these sites is hampered by several factors with regard to sample preparation, chromatography and detection. In this review, we will discuss these issues and give an overview of published methods using high-performance liquid chromatography (HPLC) for the bioanalysis of HIV protease inhibitors in CSF, PBMCs and seminal plasma.