Fascitis necrosante: experiencia de manejo en las últimas dos décadas en nuestro centro / Necrotising fasciitis: Management experience over the last two decades in our hospital

Introducción: La fascitis necrosante es una infección de partes blandas potencialmente letal que afecta principalmente a la fascia y a los planos profundos, con una tasa muy alta de mortalidad y de complicaciones graves derivadas. Objetivo: Evaluar las características clínicas y demográficas de pacientes con fascitis necrosante en nuestro centro y describir su manejo diagnóstico y terapéutico. Material y métodos: Revisión retrospectiva de historias clínicas de 21 pacientes diagnosticados de fascitis necrosante con afectación de extremidades entre enero de 2003 y febrero de 2021 en nuestro centro. Se recogieron datos demográficos y clínicos del proceso y de la evaluación del manejo en cada paciente. Resultados: De 21 pacientes incluidos, 15 eran varones (71,43%), con una edad media al diagnóstico de 54,38±19,55 años. Las comorbilidades más frecuentes fueron diabetes mellitus insulinodependiente en 7 pacientes (33,33%) y procesos oncológicos en 5 pacientes (23,81%). La infección fue monomicrobiana en 14 casos (66,66%), siendo Streptococcus pyogenes el microorganismo más frecuente; en 2 casos (9,52%) fue polimicrobiana, y en 5 pacientes (23,81%) no se identificó el patógeno causante. Todos los pacientes fueron intervenidos en nuestro centro, con una media de 4,14±3,98 cirugías, con un único caso de amputación de la extremidad afecta. La estancia hospitalaria media fue de 23,14±16,44 días, situándose la mortalidad global en el 47,62% (10 casos). Conclusiones: Pese a tratarse de una condición poco frecuente, la fascitis necrosante es una patología muy agresiva, con una elevada tasa de mortalidad, especialmente en pacientes inmunocomprometidos. Una edad avanzada y padecer un cuadro oncológico son factores potenciales de peor pronóstico en la evolución de este cuadro.(AU)

Background: Necrotising fasciitis is a potentially life-threatening soft tissue infection that mainly affects the fascia and deep planes, with a very high mortality rate and severe related complications. Aim: To evaluate clinical and demographic characteristics of patients with necrotising fasciitis in our hospital and to describe their diagnostic and therapeutic management. Material and methods: Retrospective review of medical records of 21 patients diagnosed with necrotising fasciitis with limb involvement between January 2003 and February 2021 in our hospital. Demographic data, clinical features and details of management and prognosis were collected for each patient. Results: Of 21 patients included, 15 were male (71.43%), with a mean age at diagnosis of 54.38±19.55 years. The most frequent comorbidities were insulin-dependent diabetes mellitus in 7 patients (33.33%) and a history of cancer in 5 patients (23.81%). Infection was monomicrobial in 14 cases (66.66%), with Streptococcus pyogenes being the most frequent microorganism; multiple pathogens were isolated in 2 patients (9.52%) and no microorganism was identified in 5 patients (23.81%). All patients underwent surgery at our hospital, with a mean of 4.14±3.98 surgeries. Only one patient underwent amputation of the affected limb. The mean hospital stay was 23.14±16.44 days, with an overall mortality of 47.62% (10 cases). Conclusions: Despite being a rare disease, necrotising fasciitis is a very aggressive pathology, with a high mortality rate, especially in immunocompromised patients. Advanced age and oncological disease are potential factors of worse prognosis in the evolution of this condition.(AU)

[Translated article] Necrotising fasciitis: Management experience over the last two decades in our hospital / Fascitis necrosante: experiencia de manejo en las últimas dos décadas en nuestro centro

Introducción: La fascitis necrosante es una infección de partes blandas potencialmente letal que afecta principalmente a la fascia y a los planos profundos, con una tasa muy alta de mortalidad y de complicaciones graves derivadas. Objetivo: Evaluar las características clínicas y demográficas de pacientes con fascitis necrosante en nuestro centro y describir su manejo diagnóstico y terapéutico. Material y métodos: Revisión retrospectiva de historias clínicas de 21 pacientes diagnosticados de fascitis necrosante con afectación de extremidades entre enero de 2003 y febrero de 2021 en nuestro centro. Se recogieron datos demográficos y clínicos del proceso y de la evaluación del manejo en cada paciente. Resultados: De 21 pacientes incluidos, 15 eran varones (71,43%), con una edad media al diagnóstico de 54,38±19,55 años. Las comorbilidades más frecuentes fueron diabetes mellitus insulinodependiente en 7 pacientes (33,33%) y procesos oncológicos en 5 pacientes (23,81%). La infección fue monomicrobiana en 14 casos (66,66%), siendo Streptococcus pyogenes el microorganismo más frecuente; en 2 casos (9,52%) fue polimicrobiana, y en 5 pacientes (23,81%) no se identificó el patógeno causante. Todos los pacientes fueron intervenidos en nuestro centro, con una media de 4,14±3,98 cirugías, con un único caso de amputación de la extremidad afecta. La estancia hospitalaria media fue de 23,14±16,44 días, situándose la mortalidad global en el 47,62% (10 casos). Conclusiones: Pese a tratarse de una condición poco frecuente, la fascitis necrosante es una patología muy agresiva, con una elevada tasa de mortalidad, especialmente en pacientes inmunocomprometidos. Una edad avanzada y padecer un cuadro oncológico son factores potenciales de peor pronóstico en la evolución de este cuadro.(AU)

Background: Necrotising fasciitis is a potentially life-threatening soft tissue infection that mainly affects the fascia and deep planes, with a very high mortality rate and severe related complications. Aim: To evaluate clinical and demographic characteristics of patients with necrotising fasciitis in our hospital and to describe their diagnostic and therapeutic management. Material and methods: Retrospective review of medical records of 21 patients diagnosed with necrotising fasciitis with limb involvement between January 2003 and February 2021 in our hospital. Demographic data, clinical features and details of management and prognosis were collected for each patient. Results: Of 21 patients included, 15 were male (71.43%), with a mean age at diagnosis of 54.38±19.55 years. The most frequent comorbidities were insulin-dependent diabetes mellitus in 7 patients (33.33%) and a history of cancer in 5 patients (23.81%). Infection was monomicrobial in 14 cases (66.66%), with Streptococcus pyogenes being the most frequent microorganism; multiple pathogens were isolated in 2 patients (9.52%) and no microorganism was identified in 5 patients (23.81%). All patients underwent surgery at our hospital, with a mean of 4.14±3.98 surgeries. Only one patient underwent amputation of the affected limb. The mean hospital stay was 23.14±16.44 days, with an overall mortality of 47.62% (10 cases). Conclusions: Despite being a rare disease, necrotising fasciitis is a very aggressive pathology, with a high mortality rate, especially in immunocompromised patients. Advanced age and oncological disease are potential factors of worse prognosis in the evolution of this condition.(AU)

[Translated article] Necrotising fasciitis: Management experience over the last two decades in our hospital.

BACKGROUND: Necrotising fasciitis is a potentially life-threatening soft tissue infection that mainly affects the fascia and deep planes, with a very high mortality rate and severe related complications. AIM: To evaluate clinical and demographic characteristics of patients with necrotising fasciitis in our hospital and to describe their diagnostic and therapeutic management. MATERIAL AND METHODS: Retrospective review of medical records of 21 patients diagnosed with necrotising fasciitis with limb involvement between January 2003 and February 2021 in our hospital. Demographic data, clinical features and details of management and prognosis were collected for each patient. RESULTS: Of 21 patients included, 15 were male (71.43%), with a mean age at diagnosis of 54.38±19.55 years. The most frequent comorbidities were insulin-dependent diabetes mellitus in seven patients (33.33%) and a history of cancer in five patients (23.81%). Infection was monomicrobial in 14 cases (66.66%), with Streptococcus pyogenes being the most frequent microorganism; multiple pathogens were isolated in 2 patients (9.52%) and no microorganism was identified in 5 patients (23.81%). All patients underwent surgery at our hospital, with a mean of 4.14±3.98 surgeries. Only one patient underwent amputation of the affected limb. The mean hospital stay was 23.14±16.44 days, with an overall mortality of 47.62% (10 cases). CONCLUSIONS: Despite being a rare disease, necrotising fasciitis is a very aggressive pathology, with a high mortality rate, especially in immunocompromised patients. Advanced age and oncological disease are potential factors of worse prognosis in the evolution of this condition.

Glycine receptors control the generation of projection neurons in the developing cerebral cortex.

The development of the cerebral cortex requires coordinated regulation of proliferation, specification, migration and differentiation of cortical progenitors into functionally integrated neurons. The completion of the neurogenic program requires a dynamic interplay between cell intrinsic regulators and extrinsic cues, such as growth factor and neurotransmitters. We previously demonstrated a role for extrasynaptic glycine receptors (GlyRs) containing the α2 subunit in cerebral cortical neurogenesis, revealing that endogenous GlyR activation promotes interneuron migration in the developing cortical wall. The proliferative compartment of the cortex comprises apical progenitors that give birth to neurons directly or indirectly through the generation of basal progenitors, which serve as amplification step to generate the bulk of cortical neurons. The present work shows that genetic inactivation of Glra2, the gene coding the α2 subunit of GlyRs, disrupts dorsal cortical progenitor homeostasis with an impaired capability of apical progenitors to generate basal progenitors. This defect results in an overall reduction of projection neurons that settle in upper or deep layers of the cerebral cortex. Overall, the depletion of cortical neurons observed in Glra2-knockout embryos leads to moderate microcephaly in newborn Glra2-knockout mice. Taken together, our findings support a contribution of GlyR α2 to early processes in cerebral cortical neurogenesis that are required later for the proper development of cortical circuits.

ADAM17 is a survival factor for microglial cells in vitro and in vivo after spinal cord injury in mice.

A disintegrin and metalloprotease 17 (ADAM17) is a sheddase with important substrates including tumor necrosis factor-α (TNF-α) and its receptors, the p75 neurotrophin receptor (p75NTR), and members of the epidermal growth factor family. The rationale of this study was to inhibit ADAM17-induced shedding of soluble TNF-α in order to reduce detrimental inflammation after spinal cord injury (SCI). However, using the specific ADAM17 blocker BMS-561392 in neuronal and glial cell cultures, we show that proper functioning of ADAM17 is vital for oligodendrocyte and microglia survival in a p44 MAPK-dependent manner. In contrast, genetic ablation of ADAM17 specifically increases microglial death. Surprisingly, although blocking ADAM17 in vivo does not substantially change the ratio between membrane-bound and soluble TNF-α, it increases expression of the pro-apoptotic marker Bax and microglial apoptosis while impairing functional recovery after SCI. These data suggest that ADAM17 is a key survival factor for microglial cells after SCI.

[Dysmetabolic hyperferritinemia: a new target for treatment?]. / Hyperferritinémie associée au syndrome métabolique: une nouvelle cible thérapeutique?

Dysmetabolic hyperferritinemia is currently the most frequent cause of elevated ferritin levels in the general population. Whether dysmetabolic hyperferritinemia is a cause or an effect of insulin resistance is still a matter of debate. Still, several findings have been well established: increased iron intake or elevated ferritin levels are individual risk factors for diabetes, metabolic syndrome or gestational diabetes. When in presence of dysmetabolic hyperferritinemia, a small number of randomized controlled trials have suggested that therapeutic measures aimed at reducing ferritin levels such as low red meat consumption, deferoxamin or therapeutic phlebotomies have shown a beneficial effect on glucose homeostasis, lipid profile and impaired hepatic markers observed in non-alcoholic steatohepatitis.

Independent contribution of parental migrant status and educational level to adiposity and eating habits in preschool children.

BACKGROUND/OBJECTIVE: Little is known about the precise role of parental migrant status (MS) and educational level (EL) on adiposity and various eating habits in young children. Therefore, we assessed their independent contribution in preschoolers. SUBJECTS/METHODS: Of 655 randomly selected preschoolers, 542 (5.1±0.6 years; 71% of parental MS and 37% of low parental EL) were analysed. Body composition was measured by bioelectrical impedance. Eating habits were assessed using a semiqualitative food frequency questionnaire and analysed according to five messages developed by the Swiss Society for Nutrition, based on factors implicated in childhood obesity: (1) 'Drinking water and decreasing sweetened drinks', (2) 'Eating fruit and vegetables', (3) 'Decreasing breakfast skipping', (4) 'Reducing fatty and sweet foods' and (5) 'Reducing the intake of meals and snacks in front of television'. RESULTS: Children of migrant and low EL parents had higher body fat, ate more meals and snacks while watching television and had more fruit and fatty foods compared with their respective counterparts (all P≤ 0.04). Children of low EL parents also consumed less water and vegetables compared with their counterparts (all P≤ 0.04). In most instances, we found an independent contribution of parental MS and EL to adiposity and eating habits. A more pronounced effect was found if both parents were migrants or of low EL. Differences in adiposity and eating habits were relatively similar to the joint parental data when assessed individually for maternal and paternal MS and EL. CONCLUSIONS: Parental MS and EL are independently related to adiposity and various eating habits in preschoolers.

Nutritional deterioration in cancer: the role of disease and diet.

AIMS: Under-nutrition is a major source of morbidity and mortality in cancer patients. This prospective, cross-sectional study aimed to evaluate the relative contributions of cancer staging, duration and diet on patients' nutritional deterioration. MATERIALS AND METHODS: We included 205 consecutive patients (133 men and 72 women) with head and neck, gastro-oesophageal, colon and rectum cancer, age 53 +/- 12 (33-86) years, referred for radiotherapy (primary, adjunctive to surgery, combined with chemotherapy or with palliative intent). We registered clinical variables, nutritional status (percentage of weight loss, Patient-Generated Subjective Global Assessment and body mass index), nutritional requirements, usual diet intake (diet history) and current intake (24-h recall). RESULTS: In stage III and IV, we observed a significant decrease of usual and current energy and protein intake (P=0.002), which were not observed in stage I and II. Reduction in nutritional intake was influenced by disease duration (P=0.04), but when the latter was evaluated in a multivariate analysis, current dietary intake was associated only with staging (P=0.004), thus disclosing a distinct pattern of nutritional intake between stages and diagnosis. Using a general linear model, advanced staging showed the most significant association with nutritional depletion (P=0.0001). We also found significant associations for tumour location (P=0.001), disease duration (P=0.002), nutritional intake (P=0.003) and previous surgery or chemotherapy (P=0.02). Percentage weight loss showed a consistently superior performance with regard to clinical variables and ability to detect mild to extreme nutritional changes. Patient-Generated Subjective Global Assessment had a very high sensitivity and specificity, and a strong capacity for detecting patients at nutritional risk compared with body mass index. CONCLUSIONS: Nutritional depletion is multifactorial, dependent mainly on the tumour burden of the host. Percentage weight loss is a sensitive and specific tool that can screen and identify malnutrition effectively. Its joint use with Patient-Generated Subjective Global Assessment, which establishes boundaries for nutritional therapy, will optimise the efficacy of nutritional assessment and support in cancer patients.

Comparisons of anti-human immunodeficiency virus activities, cellular transport, and plasma and intracellular pharmacokinetics of 3'-fluoro-3'-deoxythymidine and 3'-azido-3'-deoxythymidine.

3'-Fluoro-3'-deoxythymidine (FLT), a candidate anti-AIDS compound in clinical trials, showed anti-human immunodeficiency virus type 1 (HIV-1) potency (50% effective concentration, 0.0052 microM) slightly better than or equal to that of 3'-azido-3'-deoxythymidine (AZT) in MT4 cells and was threefold more potent in H9 cells. There was no FLT resistance demonstrable in the AZT-resistant HIV-1 strains. Both FLT and AZT showed low cytotoxicity for MT4 cells, with selectivity indices (efficacy/toxicity ratio) of greater than 47,000 and greater than 33,000, respectively. Cellular permeation of FLT and thymidine (dThd) was greater than that of AZT, and FLT and dThd permeated the cell membranes by a carrier-mediated mechanism as well as by simple diffusion, as indicated by the existence of nitrobenzylthioinosine-5'-monophosphate-sensitive and -insensitive components. By contrast, transport of AZT into cells was by simple diffusion. The intracellular level of the triphosphate of FLT (FLTTP) in MT4 cells was two- to threefold higher than that of AZT (AZTTP) after exposure to 1.8 microM each compound for 12 h. The elimination kinetics of FLTTP and AZTTP in HIV-1-infected MT4 cells in fresh medium showed biphasic patterns, with initial half-lives of 1.03 and 1.09 h, respectively. In phytohemagglutinin-stimulated human peripheral blood lymphocytes, the FLTTP level was increased 59-fold compared with that in unstimulated cells at 12 h, was four- to sixfold higher than the level of AZTTP in stimulated cells at 12 h, and remained four- to fivefold higher during a 4-h elimination period in fresh medium and twofold higher at the end of a 12-h elimination period. Two- to eightfold more [3H]AZT than [3H]FLT was incorporated into the host cell DNA, and both [3H]AZT and [3H]FLT remained persistently incorporated for over 24 h. The incorporated [3H]AZT and [3H]FLT were alkali labile, whereas incorporated [3H]dThd was alkali stable. Pharmacokinetics of FLT in plasma of monkeys after intravenous (i.v.) administration showed that the FLT concentration in plasma declined, with a half-life of 1.19 +/- 0.1 h; the steady-state volume of distribution was 0.93 +/- 0.2 liter/kg of body weight, and total clearance was 0.56 +/- 0.15 liter/kg. Oral bioavailability of FLT was excellent and comparable to i.v. bioavailability in terms of areas under the concentration-time curves for three monkeys. Of the total dose, 41 to 61% was excreted in urine as unchanged FLT, and only 3.2 to 7.4% of the total dose was identified as glucuronide-conjugated FLT in urine 48 h after i.v. administration to monkeys. We conclude that FLT exhibits an anti-HIV-1 potency similar to that of AZT but with slightly better selectivity of effects and with higher intracellular active metabolite levels.

Incorporation and metabolism of 2'-fluoro-5-substituted arabinosyl pyrimidines and their selective inhibition of viral DNA synthesis in herpes simplex virus type 1 (HSV-1)-infected and mock-infected Vero cells.

The incorporation and metabolism of 2'-fluoro-5-substituted arabinosyl pyrimidine analogs, and their selective inhibition of viral DNA synthesis in herpes simplex virus type 1 (HSV-1)-infected and mock-infected Vero cells were studied by HPLC and CsCl isopycnic density gradient analysis of isolated DNAs. The amounts of radiolabeled analogs incorporated as parent compound following 10 microM exposure for 4 h were 10-fold higher in HSV-1-infected vs mock-infected cells for 2'-fluoro-5-difluoromethyl-Ara-U (F2FMAU); 4.3-fold higher for 5-ethyl deoxyuridine (EdU); 2.6-fold higher for 2'-fluoro-5-methyl-Ara-U (FMAU) and 1.7-fold higher for dThd. For 2'-fluoro-5-ethyl-Ara-U (FEAU), 3.0 pmole of unchanged moiety was incorporated per 10(6) HSV-1-infected cells but no incorporation was detected in mock-infected cells. HPLC profiles showed that the percentages of radiolabeled analogs incorporated as parent compound in the DNA extracted from HSV-1-infected cells were 31.0% for F2FMAU, 99.6% for EdU, 83.5% for FEAU and 98.3% for FMAU; from mock-infected cells, they were 63.6% for F2FMAU, 96.7% for EdU, 97.3% for FMAU and no incorporation into DNA for FEAU was detected. CsCl density gradient analyses of isolated DNA showed that viral DNA synthesis was inhibited 98% by 10 microM FEAU, 92% by 10 microM F2FMAU, 90% by 2 microM FMAU and 80% by 50 microM EdU, whereas cellular DNA synthesis was inhibited by 53, 44, 61, 66 and 54%, respectively. We conclude that: (a) FEAU incorporation into host-cell DNA was not detectable but FEAU was selectively incorporated into HSV-infected cells; (b) FMAU and FEAU were metabolically stable; however, F2FMAU was extensively metabolized; (c) FEAU and F2FMAU were among the most selective inhibitors of HSV-1 DNA synthesis while allowing cellular DNA synthesis to continue.

Toxicity, elimination, and metabolism of 10-ethyl-10-deazaaminopterin in rats and dogs.

10-Ethyl-10-deazaaminopterin (10-EdAM) is an antifolate compound with greater therapeutic activity than methotrexate against transplanted tumors in mice. When given weekly for 3 weeks, the 10% lethal dose in rats was 125 mg/kg (i.p.) and in dogs it was 2.5 mg/kg (i.v.). The major histopathological findings in intoxicated animals were damage to the mucosa of the gastrointestinal tract in rats and dogs and hypocellularity of the marrow in rats. The elimination of 50 mg/kg of 10-EdAM from the plasma of rats was triexponential with a terminal phase t1/2 of 18.5 h but a mean residence time of 0.7 h. The primary route of elimination in rats was biliary secretion of parent compound and eventual excretion of the parent compound and the deglutamate metabolite in the feces; the 7-hydroxy metabolite was also present in plasma, bile, and feces. Biliary elimination was independent of dose over a 5-fold range. The elimination of 10-EdAM from the plasma of dogs was also triexponential with a mean terminal phase t1/2 of 9.1 h and a mean residence time of 2.5 h; nonrenal clearance was the primary route of elimination. The pharmacokinetic parameters were independent of dose over the range of 0.25 to 5.0 mg/kg. High tissue concentrations of 10-EdAM were observed initially in liver, kidney, and small intestine of rats, while concentrations in bone marrow were low. Some polyglutamate formation was observed in these tissues as early as 0.5 h after drug administration but declined over 72 h.

Fluorometric high-performance liquid chromatographic analysis of 10-deazaaminopterin, 10-ethyl-10-deazaaminopterin, and known metabolites.

The antifolate compounds 10-deazaaminopterin (10-dAM) and 10-ethyl-10-deazaaminopterin (10-EdAM) are therapeutically superior to methotrexate in transplanted murine tumor systems and in human tumor xenografts growing in immunodeficient "nude" mice. The increased therapeutic index of these analogs correlates with their selective uptake, retention, and polyglutamation within neoplastic cells. We have developed a fluorescence high-performance liquid chromatographic assay applicable to 10-dAM, 10-EdAM, their polyglutamate anabolites, and their 7-hydroxy (7-OH) and deglutamate catabolites. The assay is based upon the high native fluorescence of pteridine-containing compounds which contain carbon in the 10 position. The assay employs a reverse-phase C-18 column and an ascending acetonitrile gradient in 50 mM phosphate, pH 7.0. The compounds are extracted from plasma and urine with 95 +/- 7% and 98 +/- 2% recoveries, respectively, using C-18 Sep-Paks. The linear range of the assay is, for 10-dAM, 2-100 nM, and for 10-EdAM, 1-100 nM. Polyglutamated metabolites of [3H]10-EdAM isolated from L1210 cells have been separated by HPLC with identification of five derivatives (Glu 1-5) confirmed by enzymatic peak shift using serum conjugase and by quantitative correlation of fluorescence intensity, radioactivity, and titration inhibition of dihydrofolate reductase. The assay has been used successfully in pharmacokinetic analyses of plasma and urine samples from patients receiving 10-dAM and 10-EdAM. In patients who had received 10-EdAM, 7-OH-10-EdAM, and the deglutamate catabolite were also detected. This HPLC fluorescence assay is superior to the dihydrofolate reductase inhibition and binding assays with regard to specificity and precision; moreover, it can provide a means for simultaneous assay of the physiologically important anabolites and catabolites of these new antifolates.

Biotransformation and elimination of [2-14C]-1-(2-deoxy-2'-fluoro-beta-D -arabinofuranosyl)-5-iodocytosine in immunosuppressed patients with herpesvirus infections.

The metabolism of the drug [2-14C]-1-(2'-deoxy-2'-fluoro-beta-D -arabinofuranosyl)-5-iodocytosine (FIAC), a potent inhibitor of herpesvirus replication, was studied in immunosuppressed patients with herpesvirus infections. FIAC was administered intravenously by 15-min infusion and by mouth 24 h later to four patients at doses of 50 or 100 mg/m2. FIAC was cleared from the plasma primarily by biotransformation in liver, kidney, and peripheral blood, with a terminal-phase half-life of 0.92 to 1.80 h (mean, 1.36 h) after intravenous administration. The area under the concentration-time curve from zero to infinity (AUC0-infinity) for FIAC was 1.6 to 4.7% (mean, 3.4%) of the AUC0-infinity for total radioactivity. 1-(2'-Deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodouracil (FIAU) was the major metabolite; the AUC0-infinity for FIAU was 54.3 to 72.5% (mean, 63.4%) of the AUC0-infinity for total radioactivity. The terminal-phase half-life for FIAU was 3.32 to 4.49 h (mean, 3.91 h); FIAU was cleared from plasma by renal elimination and further biotransformation. lesser amounts of 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)uracil, 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)cytosine, the glucuronide conjugates of these metabolites, and the glucuronide conjugates of FIAC and FIAU were also formed. A comparison of the AUC0-infinity for total radioactivity after intravenous and oral administration suggested that nearly all of the oral dose was absorbed. Plasma levels of FIAU, also a potent inhibitor of herpesvirus replication in vitro, exceeded the 50% effective dose for herpes simplex virus and varicella-zoster virus as late as 12 h after administration of FIAC.