Students' perspectives on the use of digital versus conventional dental impression techniques in orthodontics.

BACKGROUND: Despite the increasing use of digital impressions in orthodontics, this technique does not usually form part of the learning objectives in dental training. The aim of this study was to determine how students assess the user-friendliness of intraoral scanners compared to a conventional impression technique after a theoretical and practical teaching module. METHODS: Thirty-one dental students in their seventh semester (4th year) received and conducted digital (3 M, St. Paul, NM) and conventional (alginate) impressions from: (i) the dentist's perspective, and (ii) the patient's perspective. Each student completed four questionnaires to evaluate: (i) the user-friendliness of intraoral scanning, and (ii) intraoral scanning compared to the conventional method. RESULTS: Thirty (97%) students had not previously performed digital impressions. Twenty-four (77%) students were overall "very" or "rather" satisfied with the handling of the intraoral scanning method, and 18 (58%) preferred digital to alginate impressions from the dentist's perspective. From the "patient's" perspective, the students did not report any significant differences between the two methods. However, the impression tray in conventional impressions reduced "patient" comfort significantly more than the camera in digital impressions (Z = - 3.496, p < 0.001). CONCLUSIONS: Dental students were able to practice both conventional alginate and modern digital impressions without prior knowledge of intraoral impression techniques after basic training and an introduction from dentists. Students reported a preference for the digital technique. Implementing digital intraoral impressions into undergraduate training is recommended to familiarise students with this rapidly developing digital technique at an early stage.

Women's Attitudes Toward Self-Monitoring of Their Pregnancy Using Noninvasive Electronic Devices: Cross-Sectional Multicenter Study.

BACKGROUND: Pregnancy can be distressing, particularly if expectant mothers are worried about the well-being of their fetus. Consequently, the desire for reassurance and frequent fetal monitoring is often pronounced. Smart wearable devices and telemedicine are promising tools that could assist women in self-monitoring their pregnancy at home, hence disburdening emergency departments (EDs). They present the possibility to clarify the need for urgent care remotely and offer tighter pregnancy monitoring. However, patients' acceptance of such new technologies for fetal monitoring has not yet been explored extensively. OBJECTIVE: This survey aimed to elucidate the attitudes of women toward self-monitoring of their pregnancy using noninvasive electronic devices. The technical details of the proposed devices were not specified. METHODS: A cross-sectional multicenter study was conducted at the departments of obstetrics of the University Hospitals of Heidelberg and Leipzig, Germany. All patients seen in the obstetrics clinic who were above 18 years were offered participation. We designed a survey questionnaire including validated instruments covering population characteristics, issues in current and past pregnancies, as well as attitudes toward self-monitoring of pregnancy with smart devices. RESULTS: A total of 509 pregnant women with no previous experience in telemedicine participated. Only a small minority of 5.9% (29/493) regarded self-monitoring with wearable devices as an alternative to consulting their physicians. Along these lines, only 7.7% (38/496) strongly believed they would visit the ED less often if such devices were readily available. However, if the procedure were combined with a Web-based telemetric physician consult, 13.5% (66/487) would be highly motivated to use the devices. Furthermore, significantly more women regarded it as an alternative prior to seeing a doctor when they perceived a decline in fetal movements (P<.001). Interestingly, women with university degrees had a higher propensity to engage in pregnancy self-monitoring compared with women without one (37% vs 23%; P=.001). Of the participants, 77.9% (381/489) would like smart wearable devices to measure fetal heart sounds, and 62.6% (306/489) wished to use the devices on their own. Feedback from a doctor or midwife was also very important in their choice of such devices (61.8%, 301/487 wished feedback). The intended frequency of use differed vastly among women, ranging from 13.8% (65/471) who would like to use such a device several times per day to 31.6% (149/471) who favored once per week at most. CONCLUSIONS: Our results point to a skeptical attitude toward pregnancy self-monitoring among pregnant women. Nevertheless, many women are open to using devices for pregnancy monitoring in parallel to consulting their physician. The intention to use such devices several times daily or weekly, expressed by more than half of the participants, highlights the potential of such technologies.

Chemosensitivity of various peritoneal cancer cell lines to HIPEC and PIPAC: comparison of an experimental duplex drug to standard drug regimens in vitro.

We performed an in-vitro study testing the chemosensitivity of peritoneal cancer cell lines (SW620, HCT116, MKN45, 23,132/87, OAW42) to various cytostatic drug regimens. A duplex drug, characterized by reversible linking of the antimetabolites 2'-deoxy-5-fluorouridine (5-FdU) and 3'-C-ethynylcytidine (ECyd), was compared to oxaliplatin or to cisplatin plus doxorubicin. The experiments were designed to reflect the conditions of intraperitoneal chemotherapy. CASY® (Cell Analysis System) technology was used to compare the impact of incubation temperature/duration and drug concentration on the viability of the cancer cell lines versus normal human dermal fibroblasts. Two incubation scenarios were explored: (i) hyperthermic intraperitoneal chemotherapy (HIPEC) with 1 h of incubation at 42 °C, and (ii) pressurized intraperitoneal aerosol chemotherapy (PIPAC) with several successive incubations at 37 °C. Under HIPEC conditions, oxaliplatin induced a potent temperature-dependent growth inhibition of colon cancer cells not seen with the duplex drug. Under PIPAC conditions, the duplex drug achieved the same growth inhibition at a fraction of the dose level required with oxaliplatin. Gastric and ovarian cancer cells were more sensitive to cisplatin plus doxorubicin than to the duplex drug under PIPAC conditions. The duplex drug suggests itself, notably in cases of platinum resistance, as an alternative or addition to intraperitoneal chemotherapies when platinum-based PIPAC technology is used. Using it with HIPEC technology is not recommended. Higher doses of the duplex drug will enhance growth inhibition, albeit at the cost of a severely reduced difference in chemosensitivity between tumor and normal cells. Our findings provide orientation for PIPAC-based personalized intraperitoneal chemotherapy.

Adherence to gynecological screening impacted by experienced orthodontic treatment in childhood.

BACKGROUND: Dental and cervical controls are two established screening programs in Germany. Compliance to orthodontic treatment in childhood is essential for dental health and one of the first health interventions that requires adherent behavior; therefore, it may be associated with participation in further screening programs in adulthood. However, it is not yet known whether early orthodontic treatment influences long-term screening adherence. METHODS: Using a questionnaire administered during a visit to a special dysplasia outpatient service, this case-control study evaluated women's personal history of orthodontic care, long-term satisfaction, and dental and gynecological screening adherence. Oral health status and dental anxiety were assessed with validated instruments. Cases were categorized as cervical dysplasia only (S2) or cervical dysplasia with conization (S1) and compared to healthy controls with a normal PAP smear. RESULTS: A study population of 233 participants included 132 cases and 101 controls. The control group had had orthodontic treatment during childhood more often than our study population with abnormal PAP smears (68.3% controls versus 56.1% subjects; p < 0.005). Orthodontic treatment was not associated with attending dental appointment or gynecological check-ups. However, women with an orthodontic treatment in childhood were significantly more often vaccinated against human papillomavirus than women without orthodontic treatment (p < 0.03). CONCLUSION: Data suggest that women with orthodontic treatment in childhood are more conscious about prevention strategies in adulthood; therefore, compliant behavior might be established in childhood.

A new Fluorescence-aided Identification Technique (FIT) for optimal removal of resin-based bracket bonding remnants after orthodontic debracketing.

Tooth-colored resin-based bracket bonding agents are used to fix orthodontic brackets to teeth as inconspicuously as possible. However, after debonding the brackets, these tooth-colored bonding remnants remain on the tooth surface and must be removed to prevent adverse sequelae. Various techniques can be used, all of which cause varying damage to the tooth structure, as the transition between composite and enamel is visually difficult to detect. With the fluorescence-aided identification technique (FIT) presented here, the fluorescent properties of new orthodontic composites are used for visualization, thereby allowing the tooth-colored but fluorescent resin-based bracket bonding remnants to be removed under direct view quickly and without damaging the tooth.

Impact of a cervical dysplasia and its treatment on quality of life and sexual function.

PURPOSE: In this case-control study, the impact on quality of life and sexual function in women with cervical dysplasia and conization will be evaluated, in order to address coping with such a premalignant lesion and to improve strategies for salutogenesis. METHODS: This multicenter case-control study evaluates women at special dysplasia outpatient clinic (T1) as well as 3 (T2) and 6 (T3) months after the diagnosis of a dysplasia. The women were subgrouped upon dysplasia only (S2) or dysplasia with conization (S1). Sexual function as well as cervix-related and general quality of life was assessed using validated instruments (FSFI-d, EORTC-QLQ-CX24, SF-36). RESULTS: Women with dysplasia had a lower sexual functioning than controls (FSFI: S1: 23.8 ± 9.7 (p < 0.003); S2: 25.3 ± 7.5 (p < 0.03); K: 29.1 ± 4.5) as well as a lower physical component score (SF-36: S1: 51.3 ± 8.6 (p < 0.02); S2: 51.7 ± 7.8 (p < 0.05); K: 54.2 ± 6.6) and had a significantly reduced body image (EORTC-QLQ-CX24: S1: 75.7 (p < 0.001); S2: 76.5 (p < 0.001), K:89.2). Sexual functioning was not affected by conization in the observational period over 6 months; however, sexual worry was impacted. Over temporal progression women who underwent conization worried more. Regression analysis revealed a cervical dysplasia to impact sexual function. CONCLUSION: Data suggest that women with the diagnosis of a cervical dysplasia are impaired in their sexual function as well as general and cervix-related quality of life, mostly independent of conization or further observation. To improve salutogenesis in the long run, the communication on dysplasia and its treatment strategy at the beginning, as well as part of aftercare, or psychosomatic intervention, might be treatment options for women at risk.

A Web-Based Survey Assessing the Attitudes of Health Care Professionals in Germany Toward the Use of Telemedicine in Pregnancy Monitoring: Cross-Sectional Study.

BACKGROUND: The demand for fetal monitoring and constant reassurance is high in pregnant women. Consequently, pregnant women use various health apps and are more likely to visit emergency departments due to subjective but nonurgent complaints. However, electronic health (eHealth) and mobile health (mHealth) solutions are rarely used to prevent nonurgent emergency consultations. To implement modern care solutions, a better understanding of the attitudes, fears, and hopes of health care professionals toward eHealth and mHealth is needed. OBJECTIVE: The aim of this study was to investigate the attitudes of health care professionals in obstetrics toward telemedicine. METHODS: A quantitative Web-based survey on health care professionals in obstetrics in Germany was conducted. The participants included nurses, midwives, and physicians of all age groups and job positions working in hospitals that provide various levels of health care. The questionnaire comprised 24 questions about the characteristics of the study population, views about emergency consultations in obstetrics, attitude toward telemedicine, job satisfaction, and sleeping behavior. RESULTS: In total, 244 health care professionals participated in the Web-based survey. In general, health care professionals were skeptical (170/233, 72.9%) about the use of telemedicine in obstetrics; however, 55.8% (130/233) recognized its potential. Moreover, 72% (62/86) of physicians were optimistic in using apps for pregnancy monitoring, whereas 36.1% (47/130) of nonphysicians (P<.001) were not. Significantly, more nonphysicians rejected such developments (75/130, 57.7% rejected) compared with physicians (24/86, 28%; P<.001). We also found that obstetricians with more than 10 years of work-experience are more skeptical; however, approximately 49% (18/37) of them believed that telemedicine could reduce nonurgent emergency consultations, whereas 73.2% (106/145) of obstetricians with less than 5 years of experience (P=.01) thought otherwise. Our survey revealed a high job satisfaction and a prevalence of regular sleeping problems of 45.9% (91/198) among health care professionals in obstetrics. Surprisingly, both job satisfaction and sleeping problems were independent from the number of night shifts per month (P=.77 and P=.99, respectively). Yet, 56.6% (112/198) of the survey participants thought they would be happier with their job if they had to work fewer night shifts per month. CONCLUSIONS: Our study reveals an ambivalent attitude toward the use of telemedicine among health care professionals in obstetrics in Germany at the moment. Efforts to promote the use of telemedicine should focus on nurses and midwives because these groups are the most skeptical. By contrast, particularly young physicians recognize the potential of apps in patient care and would like to use such technology in pregnancy monitoring.

How patient-selected colors for removable appliances are reflected in electronically tracked compliance (wear times and wear behavior).

OBJECTIVES: A broad spectrum of colors for removable appliances, intended to optimize acceptance of treatment and patient cooperation, have been available on the dental market for years. This is the first study to analyze how patient-selected colors are reflected in wear times and wear behavior of removable appliances. MATERIALS AND METHODS: The study included 117 children (55 girls and 62 boys) who were treated with active removable plate or functional appliances. All patients were offered to choose from 11 different colors, which were pooled into six groups (black, blue, green, yellow, pink, red) for analysis, or to combine any two to four colors ("multicolored" group) for their appliances. All appliances featured a built-in microsensor (TheraMon; MC Technology, Hargelsberg, Austria) for objective wear-time tracking. Differences between wear times were analyzed using pairwise t tests and Tukey correction. RESULTS: The longest median wear times were recorded in the blue and green groups (≈11 h/d) and the shortest ones in the red and pink groups (≈9 h/d), but they were not significantly influenced by the patient-selected colors. The median wear times involved an age-related decrease by 0.56 h/y that was statistically significant ( P = .00005). No gender-specific patterns of wear behavior were observed. CONCLUSIONS: Patient-selected colors for removable appliances can presumably improve acceptance of treatment, but they are not associated with statistically significant improvements in wear time or wear behavior.

A comparison between indirect and objective wear-time assessment of removable orthodontic appliances.

Background/Objectives: Patients do not always adhere to the wear times prescribed for removable orthodontic appliances. We evaluated the validity and usability of indirect wear-time assessment methods by comparing wear-time estimates with microelectronically measured wear times in patients with removable orthodontic appliances. Methods: Wear times of 33 expansion plates, 34 functional appliances, and 42 retention plates of patients aged 6-20 years (12.3±2.9 years, 50.5% female) were indirectly determined by practitioners using a questionnaire assessing five parameters on a 5-point Likert scale: appliance handling, appliance appearance, bite shift, tooth movement, and appliance fit. The perceived difficulty in assessing each parameter was rated. Actual wear times were evaluated with microelectronic sensors in the appliances. Results: Regression analyses revealed that practitioners' decisions about wear times varied depending on the type of appliance and criteria used, with only one standard criterion best predicting estimated wear time for each appliance. Different standard criteria were better predictors of measured wear time: 22.3% of wear-time variability was explained by expansion plate appearance, 31.2% by functional appliance handling, and 18.8% by retainer fitting. However, practitioners rated the difficulty of assessment in most cases as 'easy'. Limitations: The study was not double blinded for technical reasons, and practitioners may have considered the evaluation criteria more carefully than in normal daily practice. Conclusions: Practitioners' decisions about wear times based on standard criteria strongly vary depending on the type of appliance and criteria used.

Growth and Chemosensitivity of Gastric Adenocarcinoma and Non-Malignant Cell Lines in Response to Novel Anti-Cancer Drug Combinations.

BACKGROUND: To design novel polychemotherapy regimens for gastric adenocarcinoma therapy with wider therapeutic windows using a novel duplex drug (D-D). METHODS: Two gastric adenocarcinoma (MKN-45 and 23132/87) and 2 non-malignant (NHDF and CCL-241) cell lines were treated with different drug regimens that included different doses of the standard triple-drug combination epirubicin (E) + cisplatin (C) + 5-fluorouracil (5-FU, F), i.e. ECF, and a new D-D that combined 2'-deoxy-5-fluorouridine (5FdU) and 3'ethinylcytidine. The cells were cultured for 14 days and the effect of the drug combinations was evaluated using CASY cell counting technology. RESULTS: Overall growth inhibition of the cell lines with ECF was not cancer cell line-specific. Replacing 5-FU in ECF with a D-D resulted in greater growth inhibition of cancer cells than of the non-malignant cell lines and the inversion of the chemosensitivity of MKN-45 and 23132/87 cells. The type and quantity of the combined drug regimen determined the cytotoxicity and chemosensitivity of the cell lines. CONCLUSION: The cytotoxicity and tumour-cell specificity of standard single drugs can be markedly changed and determined using multidrug combinations that include D-Ds.

Measuring wearing times of glasses and ocular patches using a thermosensor device from orthodontics.

PURPOSE: Amblyopia is one of the most common visual disorders in children. The risk of severe visual impairment on the healthy eye is doubled in patients with amblyopia. If detected early enough, the chances of visual rehabilitation are good. Treatment consists of refractive correction and occlusion of the dominant eye. Patient compliance is an important factor and can be monitored using thermosensors. It was the goal of our study to give proof of the principle that the wearing times of glasses and patches can be measured using a comparatively small and commercially available microsensor. METHODS: Agreement between wearing times protocols of ocular patching/refractive correction and temperature measurements of thermosensors attached to the patches or glasses of three individuals were analysed using the Bland-Altman method. It was also analysed whether blinded persons could distinguish between temperature curves of patches and glasses, or temperature curves of an incubator or while worn in a pocket. RESULTS: The temperatures picked up by the microsensors indicate the beginning and the end wearing times of either glasses or ocular patches through steep temperature difference and a distinct temperature curve during measurements. Although blinded test persons were able to cleary distinguish between temperature profiles from incubator/pocket measurements compared to glasses/patching, glasses and patching curves could be discriminated correctly in only 50%. Differences between wearing time protocols and temperature measurements were within the limits of agreement as stated by the Bland-Altman plots. CONCLUSION: The TheraMon(®) microsensor can reliably measure wearing times of glasses and ocular patches without making the wearer uncomfortable, although the data are not unquestionable, especially in higher surrounding temperatures. Further studies on a larger number of individuals with different wearing profiles are needed.

Sensitivity of gastric adenocarcinoma and normal cell lines against combined or conjugated antimetabolites.

The in-vitro growth inhibition of cancer and normal cell lines caused by mixed or covalently linked antimetabolites should clarify whether the conjugation of antimetabolites influences cell sensitivity and growth inhibition in a manner that differs from an equimolar mixture of the same antimetabolites or not. Growth inhibition of the human gastric adenocarcinoma cell lines 23132/87 and MKN-45 in comparison with normal gastric intestinal CCL-241 and the dermal fibroblast cell line NHDF was evaluated using CASY technology. The cell lines were incubated with an equimolar mixture of 5-fluoro-2'-deoxyuridine (5FdU)+3'-C-ethynylcytidine (ECyd) or the covalently linked duplex drug 5FdU(5'→5')ECyd. The drug and metabolites of the assays and medium were determined semiquantitatively using high-performance liquid chromatography. The sensitivity of cancer and nonmalignant cell lines was clearly different against the duplex drug. A measure of 0.65 µmol/l 5FdU(5'→5')ECyd, for example, reduced the growth of MKN-45 or 23132/87 gastric cancer cells from 100% on day 0 to about 50 or 20% on day 10, respectively. However, under the same conditions, the growth of the nonmalignant NHDF and CCL-241 cell lines was not markedly inhibited. The cytostatic activity of the duplex drug is based on the active metabolites in and outside the cell formed by the degradation of 5FdU(5'→5')ECyd. The sensitivity of cell lines against the duplex drug depended on its ability to metabolize the duplex drug. 5FdU(5'→5')ECyd should be more advantageous for specific and efficient polychemotherapy of gastric cancer than the corresponding equimolar mixture of 5FdU+ECyd or a standard combination regime of single drugs.

Cytostatic activity of a 5-fluoro-2'-deoxyuridine-alendronate conjugate against gastric adenocarcinoma and non-malignant intestinal and fibroblast cell lines.

BACKGROUND: 5-Fluoro-2'-deoxyuridine (5-FdU), a drug against gastric cancer, was covalently linked via its nucleobase with the amino-bisphosphonate alendronate (Ale), resulting in a new antimetabolite-bisphosphonate conjugate (5-FdU-Ale), designed for bone-targeting. MATERIALS AND METHODS: The cytostatic effect of 5-FdU-Ale was evaluated in vitro compared to monomers and mixtures using CASY Technologies and the human gastric adenocarcinoma cell lines 23132/87 and MKN-45, in comparison to the intestinal CCL-241 and dermal fibroblast NHDF neonatal cell lines. RESULTS: The adenocarcinoma cell lines demonstrated a slightly higher sensitivity, with respect to the cell lines CCL-241 and NHDF, to incubation with 5-FdU-Ale. In comparison to 5-FdU, 5-FU and an equimolar mixture of Ale+5-FdU and Ale+5-FU, the cytostatic activity of the 5-FdU-Ale was markedly reduced. CONCLUSION: 5-FdU-Ale was only partially or not at all metabolized to a mixture of cytostatic metabolites in vitro. Therefore an in vivo evaluation of the conjugates is indicated.

N4-[Alkyl-(hydroxyphosphono)phosphonate]-cytidine-new drugs covalently linking antimetabolites (5-FdU, araU or AZT) with bone-targeting bisphosphonates (alendronate or pamidronate).

Amino-bisphosphonates (alendronate, pamidronate) were covalently linked in a three step synthesis, with protected and triazolylated derivatives of therapeutically used nucleoside analogs (5-FdU, araC, AZT) by substitution of their triazolyl residue. From the deprotected and chromatographically purified reaction mixtures N4-[alkyl-(hydroxyphosphono) phosphonate]-cytidine combining two differently cytotoxic functions were obtained. This new family of bisphosphonates (BPs) contains as novelty an alkyl side chain with a cytotoxic nucleoside. The BPs moiety allows for a high binding to hydroxyapatite which is a prerequisite for bone targeting of the drugs. In vitro binding of 5-FdU-alendronate (5-FdU-ale) to hydroxyapatite showed a sixfold increased binding of these BPs as compared to 5-FdU. Exploratory cytotoxic properties of 5-FdU-ale were tested on a panel of human tumor cell lines resulting in growth inhibition ranging between 5% and 38%. The determination of IC50-concentrations of the conjugate in Lewis lung carcinoma and murine macrophages showed an incubation time dependent growth inhibition with higher sensitivity towards the tumor cells. We assume that the antimetabolite-BPs can be cleaved into different active metabolites that may exert cytotoxic and other therapeutic effects. However, the underlying mechanisms of these promising new antimetabolite-BPs conjugates remain to be evaluated in future experiments.

Effect of (r)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine (H2G) and AZT-lipid-PFA on human herpesvirus-6B infected cells.

BACKGROUND: Human herpesvirus-6 (HHV-6) has been associated with a wide spectrum of diseases. (r)-9-[4-Hydroxy-2-(hydroxymethyl)butyl]guanine (H2G) is an acyclic guanosine analogue that is structurally similar to acyclovir and is in clinical development for treatment of herpesvirus infections. H2G has been found to have activity against HSV type 1, HSV type 2, and HHV-6 in lymphoblast cell lines. A new anti-viral duplex drug, 3'-azido-3'-deoxythymidylyl-(5'-->2-O)-3-O-octadecyl-sn-glycerol (AZT-lipid-PFA), linking zidovudine (AZT) and foscarnet (PFA) via a lipophilic octadecylglycerol residue (lipid) also exhibits anti-viral activities against HIV, HSV type 1 and HCMV. OBJECTIVE: To assess the efficacy of H2G and AZT-lipid-PFA conjugate against HHV-6. STUDY DESIGN: Drug-associated toxicity and proliferative response were evaluated. We conducted in vitro experiments to determine the efficacy of H2G and an AZT-lipid-PFA conjugate in interfering with expression HHV-6 viral transcript in primary human peripheral blood mononuclear cells (PBMC). RESULTS: Both H2G and AZT-lipid-PFA were effective at inhibiting expression of HHV-6 gene transcript at comparable concentrations. Additionally, while AZT-lipid-PFA treatment was toxic to cells at concentrations above 5microM, H2G treatment was associated with minimal cytotoxicity. CONCLUSION: These data suggest the potential application of these anti-viral compounds in controlling HHV-6 infection.

Synthesis and in vitro activities of a new antiviral duplex drug linking Zidovudine (AZT) and Foscarnet (PFA) via an octadecylglycerol residue.

To prepare a new antiviral duplex drug linking Zidovudine (AZT) and Foscarnet (PFA) via a lipophilic octadecylglycerol residue we condensed 1-O-4-monomethoxytrityl-3-O-octadecyl-sn-glycerol-2-hydrogenphosphonate obtained from 3-O-octadecyl-sn-glycerol with AZT by the phosphonate method. The purified condensation product was de-tritylated resulting in 3'-azido-3'-deoxythymidylyl-(5'-->2-O)-3-O-octadecyl-sn-glycerol, followed by treatment with (ethoxycarbonyl)phosphoric dichloride. The resulting 3'-azido-3'-deoxy-thymidylyl-(5'-->2)-3-O-octadecyl-sn-glycerol-1-O-(ethoxycarbonyl)phosphonate was purified by preparative RP-18 column chromatography. The antiviral duplex drug 3'-azido-3'-deoxythymidylyl-(5'-->2-O)-3-O-octadecyl-sn-glycerol-1-O-phosphonoformate trisodium salt (AZT-lipid-PFA) was obtained after alkaline cleavage of the phosphonoformate ethylester residue. The overall yield of the five step synthesis performed at gram scale was about 30%. According to a supposed pathway AZT-lipid-PFA could be cleaved to yield a mixture of different antiviral compounds such as AZT, AZT-5'-monophosphate, octadecylglycerol-AZT, PFA and octadecylglycerol-PFA, possibly producing additive and/or synergistic antiviral effects. In vitro studies showed that the duplex drug exhibits antiviral activities against HIV and especially against drug-resistant strains and clinical isolates of HSV and HCMV. The E(50) values of AZT-lipid-PFA against HIV ranged between 170 and 200 nM. The half-maximal inhibitory doses (IC(50)) against highly acyclovir (ACV)-resistant HSV isolates determined by a plaque reduction assay ranged between 1.87 and 4.59 microM. Using ganciclovir (GCV)-sensitive, GCV resistant and drug cross-resistant HCMV strains the IC(50)-values of AZT-lipid-PFA were between 2.78 and 1.18 microM. With regard to PFA, the IC(50)-value of AZT-lipid-PFA determined on a multi-drug-resistant HCMV strain was about 90-fold lower than that of PFA, demonstrating the superior antiviral effect of the duplex-drug.