BimD/SPO76 is at the interface of cell cycle progression, chromosome morphogenesis, and recombination.

BIMD of Aspergillus nidulans belongs to a highly conserved protein family implicated, in filamentous fungi, in sister-chromatid cohesion and DNA repair. We show here that BIMD is chromosome associated at all stages, except from late prophase through anaphase, during mitosis and meiosis, and is involved in several aspects of both programs. First, bimD(+) function must be executed during S through M. Second, in bimD6 germlings, mitotic nuclear divisions and overall cellular program occur more rapidly than in wild type. Thus, BIMD, an abundant chromosomal protein, is a negative regulator of normal cell cycle progression. Third, bimD6 reduces the level of mitotic interhomolog recombination but does not alter the ratio between crossover and noncrossover outcomes. Moreover, bimD6 is normal for intrachromosomal recombination. Therefore, BIMD is probably not involved in the enzymology of recombinational repair per se. Finally, during meiosis, staining of the Sordaria ortholog Spo76p delineates robust chromosomal axes, whereas BIMD stains all chromatin. SPO76 and bimD are functional homologs with respect to their roles in mitotic chromosome metabolism but not in meiosis. We propose that BIMD exerts its diverse influences on cell cycle progression as well as chromosome morphogenesis and recombination by modulating chromosome structure.

The uvsF gene region in Aspergillus nidulans codes for a protein with homology to DNA replication factor C.

The UV-sensitive mutant uvsF201 of Aspergillus nidulans shows increased spontaneous and UV-induced mutation and generally resembles mutants defective in nucleotide excision repair (NER). Fully-complementing uvsF clones were isolated from cosmid and cDNA libraries for sequencing. The uvsF gene is approximately 3.75 kb long and codes for a predicted polypeptide of 1092 amino acids (aa). Three small introns are clustered early in the coding region of the protein. A major part of the sequence shows homology to human, mouse and yeast RFC1 genes which code for the large subunit of the DNA replication factor C. The uvsF gene product may therefore function primarily in general DNA replication but in addition be required for the replication step of DNA repair. Extended sequencing of the uvsF gene region identified a second closely adjacent gene of unknown function which is divergently transcribed from a small (0.2 kb) intergenic promoter region.

Two uvs genes of Aspergillus nidulans with different functions in error-prone repair: uvsI, active in mutation-specific reversion, and uvsC, a recA homolog, required for all UV mutagenesis.

Two genes of Aspergillus nidulans are known to function in UV mutagenesis, but have been assigned to different epistasis groups: uvsC, which is also required for meiosis and mitotic recombination, and uvsI, which may have no other function. To clarify their role in error-prone repair and to investigate their interaction, uvsI and uvsC single and uvsI;uvsC double mutant strains were further tested for mutagen sensitivities and characterized for effects on mutation. Spontaneous and induced frequencies were compared in forward and reverse mutation assays. All results confirmed that uvsI and uvsC are members of different epistasis groups, and demonstrated that these uvs mutants have very different defects in UV mutagenesis. The uvsI strains showed wild-type frequencies in all forward mutation tests, but greatly reduced spontaneous and UV-induced reversion of some, but not other, point mutations. In contrast, uvsC had similar effects in all assay systems: namely pronounced mutator effects and greatly reduced UV mutagenesis. Interestingly, the uvsI;uvsC double mutant strains differed from both single mutants; they clearly showed synergism for all types of reversion tested: none were ever obtained spontaneously, nor after induction by UV or EMS (ethylmethane sulfonate). Based on these results, we conclude that uvsI is active in a mutation-specific, specialized error-prone repair process in Aspergillus. In contrast, uvsC, which is now known to show sequence homology to recA, has a basic function in mutagenic UV repair in addition to recombinational repair, similar to recA of Escherichia coli.

The mus-8 gene of Neurospora crassa encodes a structural and functional homolog of the Rad6 protein of Saccharomyces cerevisiae.

We cloned a DNA repair gene, mus-8, of Neurospora crassa and sequenced the genomic DNA and cDNA. Nucleotide-sequence analysis indicated that the mus-8 gene contains an open reading frame (ORF) of 456 bp, interrupted by three small introns. The deduced amino-acid sequence showed that the mus-8 gene encodes a 17 kDa protein which has 77.5% and 83.3% identity to the Rad6 protein of Saccharomyces cerevisiae and the rhp6(+) protein of Schizosaccharomyces pombe, respectively. The Rad6 protein is a ubiquitin-conjugating enzyme (E2) and is required for DNA repair, mutagenesis, and sporulation in yeast. Introduction of the mus-8 gene into a S. cerevisiae rad6 mutant resulted in significant recovery of DNA repair functions, especially UV-mutagenesis, and also sporulation, both of which are defective in the rad6 mutant. It is therefore postulated that mus-8 of Neurospora has a function very similar to that demonstrated for RAD6 of S. cerevisiae.

Phenotypic and epistatic grouping of hypo- and hyper-rec mus mutants in Aspergillus.

The mutants musK to musS of Aspergillus nidulans are sensitive to methyl-methanesulfonate (MMS) and several of them are meiotic-defective and alter mitotic recombination frequencies. All were found to be cross-sensitive to 4-nitro-quinoline-N-oxide (4-NQO) but unexpectedly none of them was hypersensitive to gamma-rays and few to UV light. Double mus; uvs mutants were constructed to test for interactions with uvs mutations of the four epistatic groups of Aspergillus, "UvsF", "UvsC", "UvsI", and "UvsB". All meiotic-defective mus mutations caused some lethal interactions, usually with uvsF. None of them showed epistasis with UvsF or UvsB group mutants and one, musO, may represent a new group. Three mus mutations that affect recombination were assigned to the UvsC group, namely musN and K, and also musL which is recombination-defective and closely resembles uvsC. While uvsC mutants are mutators and lack UV-mutagenesis, most mus mutants had no effects on mutation. Only musR, which appeared epistatic with uvsI, showed reduced UV-reversion frequencies similar to uvsI. The recombination-proficient mus mutants appeared to be epistatic with more than one group, but in several cases sensitivities were slight and overlaps insufficient to obtain corroborating results with MMS and 4-NQO.

Mutation in the bimD gene of Aspergillus nidulans confers a conditional mitotic block and sensitivity to DNA damaging agents.

Mutation in the bimD gene of Aspergillus nidulans results in a mitotic block in anaphase characterized by a defective mitosis. Mutation in bimD also confers, at temperatures permissive for the mitotic arrest phenotype, an increased sensitivity to DNA damaging agents, including methyl methanesulfonate and ultraviolet light. In order to better understand the relationship between DNA damage and mitotic progression, we cloned the bimD gene from Aspergillus. A cosmid containing the bimD gene was identified among pools of cosmids by cotransformation with the nutritional selective pyrG gene of a strain carrying the recessive, temperature-sensitive lethal bimD6 mutation. The bimD gene encodes a predicted polypeptide of 166,000 daltons in mass and contains amino acid sequence motifs similar to those found in some DNA-binding transcription factors. These sequences include a basic domain followed by a leucine zipper, which together are called a bZIP motif, and a carboxyl-terminal domain enriched in acidic amino acids. Overexpression of the wild-type bimD protein resulted in an arrest of the nuclear division cycle that was reversible and determined to be in either the G1 or S phase of the cell cycle. Our data suggest that bimD may play an essential regulatory role relating to DNA metabolism which is required for a successful mitosis.

uvsI mutants defective in UV mutagenesis define a fourth epistatic group of uvs genes in Aspergillus.

Three UV-sensitive mutations of A. nidulans, uvsI, uvsJ and uvsA, were tested for epistatic relationships with members of the previously established groups, here called the "UvsF", "UvsC", and "UvsB" groups. uvsI mutants are defective for spontaneous and induced reversion of certain point mutations and differ also for other properties from previously analyzed uvs types. They are very sensitive to the killing effects of UV-light and 4-NQO (4-nitro-quinoline-N-oxide) but not to MMS (methylmethane sulfonate). When double- and single-mutant uvs strains were compared for sensitivity to these three agents, synergistic or additive effects were found for uvsI with all members of the three groups. The uvsI gene may therefore represent a fourth epistatic group, possibly involved in mutagenic repair. On the other hand, uvsJ was clearly epistatic with members of the UvsF group and fitted well into this group also by phenotype. The uvsA gene was tentatively assigned to the UvsC group. uvsA showed epistatic interactions with uvsC in all tests, and like UvsC-group mutants is UV-sensitive mainly in dividing cells. However, the uvsA mutation does not cause the defects in recombination and UV mutagenesis typical for this group.

Esmolol is more effective than sodium nitroprusside in reducing blood loss during orthognathic surgery.

The goal of this study was to compare the efficacy of esmolol and sodium nitroprusside (SNP) as primary drugs for producing controlled hypotension and limiting blood loss during orthognathic surgery. Thirty ASA physical status I and II patients (mean age 22 yr) undergoing LeFort I maxillary osteotomies were randomly assigned to receive either esmolol (n = 15) or SNP (n = 15) as the primary drug to induce hypotension. All patients received a balanced anesthetic technique including isoflurane, with controlled hypotension during the downfracture of the maxilla. Patients assigned to the esmolol treatment group received boluses of 500 micrograms/kg of esmolol, followed by a continuous infusion of 100-300 micrograms.kg-1.min-1, and the SNP treatment group received a continuous infusion of SNP at 0.25-4.00 micrograms.kg-1.min-1; both infusions were titrated to obtain a mean arterial blood pressure within the target range of 55-65 mm Hg. The mean arterial blood pressure during the hypotensive period was 58.7 +/- 0.7 (mean +/- SEM) and 61.8 +/- 0.4 mm Hg for esmolol and SNP, respectively (P less than 0.001). In addition, 40% +/- 4% of the observed values in the esmolol group and 53% +/- 3% in the SNP group were outside the target range for mean arterial blood pressure (difference significant at P less than 0.05), and a greater proportion of the deviations were above 65 mm Hg in the SNP group than in the esmolol group (0.64 vs 0.46, respectively, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of mutagen-sensitive mus mutations on spontaneous mitotic recombination in Aspergillus.

Methyl methane-sulfonate (MMS)-sensitive, radiation-induced mutants of Aspergillus were shown to define nine new DNA repair genes, musK to musS. To test mus mutations for effects on mitotic recombination, intergenic crossing over was assayed between color markers and their centromeres, and intragenic recombination between two distinguishable adE alleles. Of eight mutants analyzed, four showed significant deviations from mus+ controls in both tests. Two mutations, musK and musL, reduced recombination, while musN and musQ caused increases. In contrast, musO diploids produced significantly higher levels only for intragenic recombination. Effects were relatively small, but averages between hypo- and hyperrec mus differed 15-20-fold. In musL diploids, most of the rare color segregants resulted from mitotic malsegregation rather than intergenic crossing over. This indicates that the musL gene product is required for recombination and that DNA lesions lead to chromosome loss when it is deficient. In addition, analysis of the genotypes of intragenic (ad+) recombinants showed that the musL mutation specifically reduced single allele conversion but increased complex conversion types (especially recombinants homozygous for ad+). Similar analysis revealed differences between the effects of two hyperrec mutations; musN apparently caused high levels solely of mitotic crossing over, while musQ increased various conversion types but not reciprocal crossovers. These results suggest that mitotic gene conversion and crossing over, while generally associated, are affected differentially in some of the mus strains of Aspergillus nidulans.

Cloning of the DNA repair gene, uvsF, by transformation of Aspergillus nidulans.

As a first step in the cloning of the DNA repair gene uvsF of Aspergillus nidulans, uvsF pyrG double mutant strains were transformed with a genomic library which carried the complementing Neurospora pyr-4 gene in the vector. Rare pyr+ uvs+ cotransformants were obtained on media lacking pyrimidines, overlayed with MMS (methyl-methane sulfonate) to which uvsF is hypersensitive. Among MMS-resistant transformants, Southerns revealed two types which showed single bands of different sizes when BglII-digested genomic DNA was probed with the vector. Both types produced uvsF- recombinants without vector sequences in homozygous crosses, but only those with the larger band also produced haploid uvs+ progeny. Using BglII-digested genomic DNA to transform Escherichia coli, plasmids of the corresponding two sizes could be rescued. Their inserts had a short internal region in common, giving evidence of rearrangement(s). In secondary transformation of uvsF mutants, only the plasmids with the larger insert showed complementation and these were used to screen Aspergillus libraries. Three types of genomic and two overlapping cDNA clones were identified. The cDNAs hybridized not only to each other, but also to the common region of the rescued plasmids. Therefore, cDNA subclones were used to map the putative uvsF sequences to a short segment in one genomic clone. In Northerns, the complementing large plasmid hybridized to three mRNAs, while the cDNA subclone identified one of these as the probable uvsF message.

Botran and bleomycin induce crossing-over, and bleomycin also increases aneuploidy in diploid strains of Aspergillus.

Both bleomycin, an antineoplastic drug, and botran (2,6-dichloro-4-nitro-aniline), a fungicide, are known to inhibit growth and induce genetic segregation in diploid tester strains of Aspergillus nidulans when present in agar media. To identify primary effects, samples of induced apparent crossover types were analysed in detail. For both compounds, coincident and consecutive events of mitotic crossing-over were found to be very frequent and such events showed a random distribution among isolated colour sectors. In the case of botran, a thorough search for imbalanced precursor types was negative and recessive lethals were found only rarely. Such segregants are therefore unlikely the result of terminal deletions. For bleomycin, induction of reciprocal crossing-over was confirmed by treatments of germinating conidia. On plating to normal growth medium, crossover segregants showed up as coloured half- or quarter-colonies, including some "twin spots". Whole coloured colonies were also frequent and these increased with dose levels which caused decreasing survival and increasing frequencies of abnormal colonies. Analysis of large fractions of such "abnormals" identified aneuploids in all cases. While botran, in plate tests, also increased haploid segregants and disomic precursors could be found, tests of germinating conidia "in liquid" were inconclusive, because botran is insoluble in water. Some increases of aneuploids were observed, but only when botran and the solvent DMSO both were present at increased levels.

Endo-exonuclease of Aspergillus nidulans.

Endo-exonuclease (EE) has been found in both active and inactive, but trypsin-activatable, forms in Aspergillus nidulans. Active EE was present mainly in nuclei, mitochondria, and vacuoles, while trypsin-activatable EE was mainly in the cytosol. The active form accounts for over 90% of the neutral deoxyribonuclease activity extracted from mycelia. A single strand (ss) DNA-binding EE associated with a 28 kilodalton (kDa) polypeptide was partially purified and characterized. It was found to closely resemble, in size and enzymological properties, the ss-DNA-binding EE previously purified from Neurospora crassa. Aspergillus nidulans EE was also found to be immunochemically related to the N. crassa EE and, like that enzyme, was probably derived from a polypeptide of 90 kDa or larger through proteolysis during extraction and purification. It had divalent metal ion-dependent (Mg2+, Mn2+, or Zn2+) activity on both DNA and RNA, which ultimately produced small 5'-P-terminated oligonucleotides. The nuclease activity was mixed endo- and exo-nucleolytic with ss-DNA as substrate, but largely exonucleolytic with double strand (ds) DNA. Superhelical phi X-174 DNA was nicked by EE to form relaxed circular and then linear ds-DNA, which was rapidly degraded to shorter fragments. Linearized pBR322 DNA was extensively nicked internally under conditions where there was relatively low exonuclease activity, but this nicking required that 5'-P-termini be present on the linear ds-DNA. The levels of active EE found in extracts of two recombination-deficient mutants of A. nidulans, uvsC and uvsE, dit not differ significantly from those in extracts of the wild type.

A single, phosphate-repressible deoxyribonuclease, DNase A, secreted in Aspergillus nidulans.

High levels of nuclease activities were identified in filtrates of Aspergillus cultures after growth in low-but not in high-phosphate media. Deoxyribonuclease activities, characterized extensively by column chromatography, showed a coincident single peak for ss- and ds-DNase which was distinct from the peak for RNase. Both ss-DNase and ds-DNase are endonucleolytic and showed the highest activity in the presence of Ca2+ and Mn2+ (at pH 8.0). They also showed identical heat sensitivities suggesting that a single, phosphate-repressible DNase was secreted. This enzyme, therefore, corresponds to the well-characterized extracellular DNase A of Neurospora. However, the Aspergillus DNase A did not cross-react with antisera to secreted Neurospora nucleases and showed different chromatographic properties, and active peptides of different sizes were visualized on DNA activity gels. The increasing derepression of Aspergillus DNase A by decreasing phosphate levels was similar to that of secreted alkaline phosphatase and these increases were both abolished by the regulatory mutant palcA.

Sensitivity to bleomycin and hydrogen peroxide of DNA repair-defective mutants in Neurospora crassa.

Mutations were induced in Neurospora which cause increased sensitivity to MMS (methyl methane-sulfonate) and other mutagens. Genetic analysis of such mus demonstrated that some of them defined new DNA repair genes (mus-21, and mus-27 to mus-30), while others represented new alleles in previously known genes. To characterize them further, and especially to identify rec- types which have not yet been found in this species, many MMS-sensitive strains were tested for cross-sensitivities to bleomycin (BLM) and to hydrogen peroxide (H2O2) to which some rec- of other species are hypersensitive. In Neurospora, many of the MMS-sensitive mutants were found to be cross-sensitive to BLM and frequently these were also hypersensitive to ionizing radiation. Bleomycin sensitivity was demonstrated for all alleles of 10 different genes, 4 of them new ones, with mus-27 being the most sensitive of the latter (resembling uvs-6; Koga and Schroeder, 1987, Mutation Res., 183, 139). In contrast, very few of the MMS-sensitive mutants were hypersensitive to H2O2 and, in general, results of H2O2 tests were variable and differences between strains small. However, consistent deviations from wild type were observed in a few cases (most clearly for mus-9 and mus-11) when results from treatments of germinating conidia were compared with those of non-growing ones.

MMS-induced primary aneuploidy and other genotoxic effects in mitotic cells of Aspergillus.

The possibility of more than 1 target for genotoxic effects of methyl methanesulphonate (MMS) was investigated, using mitotic test systems of the fungus Aspergillus. Haploid and diploid strains were exposed, either as dormant conidia or during mitosis, and analysed for induced aneuploidy and effects on genetic segregation. MMS treatment of haploid strains resulted in dose-dependent increases of stable mutants with altered phenotypes and semi-stable unbalanced aberrations (presumably duplications). In addition, but only in dividing cells, MMS induced unstable aneuploids. These mostly were hyperhaploid with few extra chromosomes and could be identified by comparison with standard disomic phenotypes. When well-marked diploids were treated 3 types of effect could be distinguished, using genetic and phenotypic criteria: (1) Clastogenic and mutagenic effects which caused dose-dependent increases of partial aneuploids with various abnormal phenotypes. These showed secondary genetic segregation of all types and produced euploid normal sectors by eliminating damaged chromosome segments. In addition, but only in dividing nuclei, MMS induced 2 types of segregation: (2) Reciprocal crossing-over at high frequency, recognisable as half or quarter colonies of mutant colour and in some cases as 'twin spots' (i.e., complementary pairs); (3) Trisomics and other aneuploids which showed characteristic phenotypes and expected segregation of markers: the types recovered indicate random malsegregation of chromosomes (occasional deviations resulted from coincidence with induced crossing-over). These results suggest that MMS may have 2 (or more) targets for genotoxic effects: DNA, as evident from induced mutations and aberrations, and from induced recombination in dividing cells; some non-DNA target (nucleotide or protein) essential for nuclear division and susceptible to alkylation, resulting in malsegregation and primary aneuploidy.

Alterations in cerebrospinal fluid uridine, hypoxanthine, and xanthine in head-injured patients.

1. Examination of the cerebrospinal fluid (CSF) of head-injured patients reveals that the concentration of intraventricular xanthine is elevated and that of uridine is decreased relative to those of adult lumbar CSF. 2. No correlations were observed between CSF lactate and CSF hypoxanthine, xanthine, or uridine, suggesting that changes in purine metabolites and the pyrimidine nucleoside do not index similar cellular events as does lactic acid production. 3. Ventricular CSF from hydrocephalic infants had uridine and hypoxanthine concentrations not significantly different from those of normal adult lumbar CSF, but xanthine was significantly elevated. 4. Since uridine has anticonvulsant properties and is a crucial substrate for cerebral metabolism, it may be useful to evaluate this pyrimidine for use in the management of patients with head injury.

Pulse oximetry: evaluation of accuracy during outpatient general anesthesia for oral surgery.

Pulse oximetry has been shown to be accurate under steady state conditions. In this study, the accuracy of four pulse oximeters are evaluated and compared during outpatient general anesthesia for third molar extractions. The oximeters evaluated are the Nellcor N-100, the Ohmeda 3700, the Novametrix model 500, and the Bird 4400 portable pulse oximeter.Ultralight general anesthesia for oral surgery presents a unique challenge for respiratory monitoring in that patients are often not intubated and commonly experience periods of hyper- and hypoventilation. Airway obstruction, apnea, and laryngospasm may occur easily and patients often vocalize and move during surgery. Because hypoxemia is the primary cause of morbidity and mortality during anesthesia, an accurate, continuous, and noninvasive monitor of oxygenation is critical to risk management.Twenty ASA class I and II patients underwent outpatient general anesthesia for third molar removal using nitrous oxide-oxygen, midazolam, fentanyl, and methohexital. Arterial blood samples were obtained at five-minute intervals during anesthesia, as well as any time a desaturation of >5% occurred, for measurement of arterial SaO(2) with an IL282 CO-Oximeter. These values were compared with simultaneously recorded saturations observed for each pulse oximeter. A total of 122 arterial samples were obtained over a range of PaO(2) from 52-323 mm Hg and observed saturations of 70-100%.The Bird 4400 portable pulse oximeter proved to be the most accurate and reliably predicted arterial saturation under these conditions (y = 1.03x - 2.8, r = 0.85). The Novametrix model 500 pulse oximeter also demonstrated a high degree of accuracy by linear regression analysis, but displayed the lowest correlation coefficient (spread of data points) overall (y = 0.97x + 2.8, r = 0.80.) The Nellcor N-100 pulse oximeter also proved to be highly accurate. (y = 1.05x - 4.1, r = 0.84.) In contrast, regression analysis of the observed saturations obtained with the Ohmeda 3700 pulse oximeter revealed that this unit significantly underestimated arterial saturation (y = 1.20x - 19.6, r = 0.83.)This study demonstrates that despite the rigorous conditions imposed by outpatient general anesthesia for oral surgery, three of the pulse oximeters tested were linearly accurate in predicting arterial oxyhemoglobin saturation over the range of 70-100%. The Ohmeda 3700 was found to significantly underestimate arterial saturation.

Absence of symptoms with carboxyhemoglobin levels of 16-23%.

It has been generally accepted that carboxyhemoglobin levels between 10-20% produce mild headaches, dizziness and/or nausea. Experimental double blind exposures of 18 healthy, nonsmoking young men at rest to 7,000-24,000 ppm CO, designed to elevate COHb to 15-20% in 3-5 minutes, were followed by exposure to 232 ppm CO designed to maintain COHb level for a total of 130 minutes. Resulting COHb values were 16-23%. These COHb values did not produce significantly more symptoms (as reported in an open-ended questioning) than reported in the control group (n = 23). Subjects were especially queried about headache, dizziness and nausea. The symptoms which were previously reported in clinical studies of CO poisoning may have resulted from CO exposure in combination with (a) exposure to other substances, (b) stress due to the event that precipitated medical attention or (c) higher COHb levels before the first blood sample was taken.

MMS sensitivity of all amino acid-requiring mutants in aspergillus and its suppression by mutations in a single gene.

All available amino acid-requiring mutants of Aspergillus nidulans were found to be hypersensitive to MMS (methyl methanesulfonate) to various degrees. On MMS media, secondary mutations could be selected which suppress this MMS sensitivity but do not affect the requirement. Many such mutations were analyzed and found to be alleles of one gene, smsA (= suppressor of MMS sensitivity), which mapped distal on the right arm of chromosome V. This gene is more likely to be involved in general regulation of amino acid biosynthesis than MMS uptake, since a variety of pathway interactions were clearly modified by smsA suppressors in the absence of MMS.

Use of capnography and transcutaneous oxygen monitoring during outpatient general anesthesia for oral surgery.

The combination of the capnograph (respired CO2 monitor) and the transcutaneous oxygen monitor was evaluated as a non-invasive system for monitoring of respiratory function in 10 ASA class I patients undergoing ultralight general anesthesia for removal of third molars. Capnography proved to be a sensitive and accurate method for detecting apnea and airway obstruction using the continuous display of the CO2 waveform. All episodes of apnea or obstruction were immediately detected as the respired CO2 level fell to zero baseline. The end-tidal CO2 (PetCO2) obtained via nasal prong sampling was not significantly different from the PaCO2. PetCO2 values served as useful indicators of hypoventilation. During steady-state conditions of respiration, transcutaneous oxygen tensions (PtcO2) correlated well with simultaneously measured PaO2 (r = 0.93). However, during any period when oxygenation was rapidly changing (step increase in FIO2, step decrease in FIO2, or apnea) the PtcO2 lagged behind changes in PaO2 even after a five-minute equilibration period, thereby not accurately reflecting the true state of oxygenation. Consequently, the transcutaneous oxygen monitor does not appear to be optimal as a respiratory monitor in the setting of ultralight general anesthesia where rapid, critical changes in oxygenation must be detected without delay.