Asia-Pacific multicentre randomized trial of laparoscopic versus open major hepatectomy for hepatocellular carcinoma (AP-LAPO trial).

BACKGROUND: Hepatocellular carcinoma is the sixth most common malignancy in the world. Major hepatectomy (resection of greater than or equal to three liver segments) is needed if a tumour is large or close to major blood vessels. Despite low mortality, open major hepatectomy is associated with high rates of tumour recurrence that limits survival. Laparoscopic major hepatectomy has been proposed as an alternative approach with potential oncological benefits. This study compares laparoscopic major hepatectomy with open major hepatectomy for hepatocellular carcinoma in a randomized trial. METHODS: The Asia-Pacific multicentre randomized trial of laparoscopic versus open major hepatectomy for hepatocellular carcinoma (AP-LAPO trial) is an open-labelled multicentre randomized trial to be conducted in five centres in the Asia-Pacific region. The study will test the hypothesis that laparoscopic major hepatectomy for hepatocellular carcinoma is associated with less tumour recurrence and better survival compared with open major hepatectomy; the primary outcome being 2-year recurrence-free survival. Secondary outcomes include hospital mortality, postoperative complications according to the Clavien-Dindo classification, time to functional recovery, quality of life, long-term survival, and postoperative serum surgical stress-related cytokines. RESULTS AND CONCLUSION: The AP-LAPO trial will determine whether laparoscopic major hepatectomy offers oncological benefits to patients with hepatocellular carcinoma compared with open major hepatectomy. REGISTRATION NUMBER: NCT04852211 (http://www.clinicaltrials.gov) registered on 21 April 2021. PROTOCOL VERSION: AP-LAPO trial version 01 (1 December 2021).

Family Experiences with the Diagnosis of Autism Spectrum Disorder: System Barriers and Facilitators of Efficient Diagnosis.

This paper examines family experiences with the efficiency of ASD diagnosis. Children were age 8 or younger with ASD (n = 450). Outcomes were delay from first parent concern to diagnosis, shifting diagnoses, and being told child did not have ASD. Predictors were screening, travel distance, and problems finding providers. Logit models were used to examine associations. Screening was associated with reduced delay in diagnosis; problems finding providers were associated with greater delay. Screening, travel distance, and delay in diagnosis were associated with shifting diagnoses and being told child did not have ASD. Physician and parent training in communication and addressing mental health professional shortages and maldistribution may improve the diagnosis experiences of families of children with ASD.

Sequence analysis of the equine ACTN3 gene in Australian horse breeds.

The sarcomeric α-actinins, encoded by the genes ACTN2 and ACTN3, are major structural components of the Z-line and have high sequence similarity. α-Actinin-2 is present in all skeletal muscle fibres, while α-actinin-3 has developed specialized expression in only type 2 (fast, glycolytic) fibres. A common single nucleotide polymorphism (SNP) in the human ACTN3 gene (R577X) has been found to influence muscle performance in elite athletes and the normal population. For this reason, equine ACTN3 (eACTN3) is considered to be a possible candidate that may influence horse performance. In this study, the intron/exon boundaries and entire coding region of eACTN3 have been sequenced in five Australian horse breeds (Thoroughbred, Arabian, Standardbred, Clydsdale and Shire) and compared to the eACTN3 GenBank sequence. A total of 34 SNPs were identified, of which 26 were intronic and eight exonic. All exonic SNPs were synonymous; however, five intronic SNPs showed significant differences between breeds. A total of 72 horses were genotyped for a SNP located in the promoter region of the eACTN3 gene (g. 1104 G>A) which differed significantly between breed groups. We hypothesize that this polymorphism influences eACTN3 expression and with further studies may provide a novel marker of horse performance in the future.

The importance of interpersonal communication in poison centers.

BACKGROUND: Poison control center (PCC) personnel face many challenges in communicating with callers and with each other. The purpose of this study was to identify interpersonal communication issues that affect the work environment within PCCs. METHODS: As part of a larger questionnaire study distributed electronically to members of the American Association of Poison Control Centers (AAPCC) to assess communication training needs for PCCs, three questions were included to assess interpersonal communication within the work environment: (1) How important is interpersonal communication within your center to a positive work environment? (not at all to extremely important, 1-7); (2) How disruptive is interpersonal communication to your work? (not at all to extremely disruptive, 1-7); and (3) What communication issues do you find most disruptive to your work? (free-text response). Descriptive and qualitative content analyses were used to identify themes in responses. RESULTS: A total of 537 responses were received from SPIs, directors, medical directors, and other PCC staff. Interpersonal communication within the PCC was rated as extremely important to a positive work environment (median = 7 and IQR = 6-7; 62.3% rated as extremely important). Interpersonal communication was rated as less than moderately disruptive on average (median = 3 and IQR = 2-4). Free-text responses were received from 335 (62%) respondents. Free-text comments were broadly categorized as relating to PCC personnel and work environment and issues related to PCC callers. Categories that emerged from the PCC personnel and work environment category included the following: poor interpersonal communication (n = 104; 31%); background noise (n = 96; 29%); poor work procedures (n = 51; 15%); and poor management communication (n = 38; 11%). CONCLUSION: Interpersonal communication within PCCs was considered to be important for a positive work environment. Although not found to be strongly disruptive by most respondents, several specific interpersonal communication issues were identified by PCC personnel as disruptive to their work.

Psychometric evaluation of the Chinese version of the Activities of Daily Living Questionnaire (ADLQ-CV).

BACKGROUND: This study examines the psychometric properties of the Chinese version of the Activities of Daily Living Questionnaire (ADLQ-CV) in a sample of older Hong Kong Chinese adults with dementia. METHOD: The ADLQ-CV was administered to primary family caregivers of 125 community-dwelling individuals with dementia. Assessments were then made of the scale's reliability, validity and factor structure. RESULTS: Factor analysis yielded six factors that closely resembled the six subscales proposed in the original scale. The ADLQ-CV demonstrated excellent convergent validity with the Chinese version of the Disability Assessment for Dementia (rp = -0.92, p < 0.001). The internal consistency of the ADLQ-CV was good (Cronbach's alpha = 0.81). Excellent test-retest reliability (ICC = 0.998) and inter-rater reliability (ICC = 0.997) of the ADLQ-CV were obtained. The ADLQ-CV showed a significant negative association with global mental states (rp = -0.80, p < 0.001), but it did not correlate with the age or educational level of individuals with dementia. CONCLUSION: The findings suggest that the ADLQ-CV is a valid and reliable instrument for evaluating the functional abilities of Hong Kong Chinese people with dementia. The brevity and simplicity of administration make it a potentially useful tool for routine assessment of functional status of people with dementia in community or hospital outpatient settings.

Dual-tracer PET/CT imaging in evaluation of metastatic hepatocellular carcinoma.

UNLABELLED: We have reported previously that (11)C-acetate ((11)C-ACT) PET was complementary to (18)F-FDG PET in the evaluation of primary hepatocellular carcinoma (HCC) in relation to the degree of tumor cellular differentiation. In this retrospective study, our goals were to further explore the complementary role of (11)C-ACT and (18)F-FDG PET in the detection of metastatic HCC disease, to evaluate the tracer characteristics of individual organ metastasis, to identify the risk factors of metastasis, and to evaluate how these results could affect patient management. METHODS: One hundred twenty-one patients were selected for this study. All patients had undergone a "dual-tracer" PET/CT same-day protocol with (11)C-ACT PET/CT followed by (18)F-FDG PET/CT. Sets of criteria were chosen to define "metastasis" and "no metastasis" on a patient basis. The patients considered as true-positive (n = 97) were then divided into 4 groups on the basis of their primary HCC tracer avidity: (18)F-FDG-avid group, (11)C-ACT-avid group, (18)F-FDG- and (11)C-ACT-avid group, and a posttreatment group with metastasis but no baseline dual-tracer PET characterization of the primary tumor and no hepatic recurrence. RESULTS: On a patient basis, dual-tracer PET/CT had a sensitivity of 98%, a specificity of 86%, a positive predictive value of 97%, a negative predictive value of 90%, and an accuracy of 96% in the detection of HCC metastasis. On a lesion basis, 273 metastatic HCC lesions considered as true-positive were detected and categorized according to the organ or site of metastasis: lymph node (abdominal and thoracic, 49%), lung (32%), bone (8%), and others (10%). The lesion-based and patient-based detection sensitivities were 60% and 64%, respectively, by (11)C-ACT and 77% and 79%, respectively, by (18)F-FDG, and they were complementary. In analyzing lesion tracer avidity, there was a positive statistical correlation between primary HCC avidity with the general tendency of metastasis. Clinically significant changes in management were found in patients with true-positive metastasis, of whom 19% were affected by (11)C-ACT PET alone. Dual-tracer PET/CT was more effective than single-tracer PET/CT in identifying candidates for curative therapy (negative predictive value of dual-tracer, (18)F-FDG, and (11)C-ACT PET/CT: 90%, 49%, and 37%, respectively). CONCLUSION: This study confirmed that (18)F-FDG PET/CT is useful in the evaluation of HCC metastasis, although its role in the diagnosis of primary HCC is more limited. Dual-tracer PET/CT had an incremental value and complementary advantage when compared with single-tracer imaging in the evaluation of HCC metastasis.

Control of Lactobacillus contaminants in continuous fuel ethanol fermentations by constant or pulsed addition of penicillin G.

The addition of penicillin G to combat microbial contamination in continuous fuel alcohol fermentations was performed using both continuous and pulsed addition regimes. In continuous fermentations where both Saccharomyces cerevisiae and Lactobacillus paracasei were present, the mode of addition of penicillin G determined final numbers of viable L. paracasei. When the same overall average concentration of penicillin G was added in both pulsed and continuous modes, the initial viable number of L. paracasei (8.0 x 10(9) cfu ml(-1)) decreased to a greater degree (1.02 x 10(5) cfu ml(-1) L. paracasei) when penicillin G was pulsed at 6 h frequencies at an overall average concentration of 2,475 U/l than when penicillin G was added continuously at 2,475 U/l (2.77 x 10(5) cfu ml(-1) L. paracasei). Pulsed additions over longer frequencies at 2,475 U/l were not as effective in reducing viable bacteria. Viable yeasts increased during both treatment conditions by more than 2-fold. The two addition regimes also eliminated the 40% decrease in ethanol concentration caused by the intentional bacterial infection. Although there was 3 times more bacterial death with 6 h pulsed additions compared to continuous additions of penicillin G at 2,475 U/l, there was, by that point, no practical difference in either final ethanol concentration or relative ethanol recovery.

Influence of medium buffering capacity on inhibition of Saccharomyces cerevisiae growth by acetic and lactic acids.

Acetic acid (167 mM) and lactic acid (548 mM) completely inhibited growth of Saccharomyces cerevisiae both in minimal medium and in media which contained supplements, such as yeast extract, corn steep powder, or a mixture of amino acids. However, the yeast grew when the pH of the medium containing acetic acid or lactic acid was adjusted to 4.5, even though the medium still contained the undissociated form of either acid at a concentration of 102 mM. The results indicated that the buffer pair formed when the pH was adjusted to 4.5 stabilized the pH of the medium by sequestering protons and by lessening the negative impact of the pH drop on yeast growth, and it also decreased the difference between the extracellular and intracellular pH values (Delta(pH)), the driving force for the intracellular accumulation of acid. Increasing the undissociated acetic acid concentration at pH 4.5 to 163 mM by raising the concentration of the total acid to 267 mM did not increase inhibition. It is suggested that this may be the direct result of decreased acidification of the cytosol because of the intracellular buffering by the buffer pair formed from the acid already accumulated. At a concentration of 102 mM undissociated acetic acid, the yeast grew to higher cell density at pH 3.0 than at pH 4.5, suggesting that it is the total concentration of acetic acid (104 mM at pH 3.0 and 167 mM at pH 4.5) that determines the extent of growth inhibition, not the concentration of undissociated acid alone.

Effects of acetic acid and lactic acid on the growth of Saccharomyces cerevisiae in a minimal medium.

Specific growth rates (mu) of two strains of Saccharomyces cerevisiae decreased exponentially (R2 > 0.9) as the concentrations of acetic acid or lactic acid were increased in minimal media at 30 degrees C. Moreover, the length of the lag phase of each growth curve (h) increased exponentially as increasing concentrations of acetic or lactic acid were added to the media. The minimum inhibitory concentration (MIC) of acetic acid for yeast growth was 0.6% w/v (100 mM) and that of lactic acid was 2.5% w/v (278 mM) for both strains of yeast. However, acetic acid at concentrations as low as 0.05-0.1% w/v and lactic acid at concentrations of 0.2-0.8% w/v begin to stress the yeasts as seen by reduced growth rates and decreased rates of glucose consumption and ethanol production as the concentration of acetic or lactic acid in the media was raised. In the presence of increasing acetic acid, all the glucose in the medium was eventually consumed even though the rates of consumption differed. However, this was not observed in the presence of increasing lactic acid where glucose consumption was extremely protracted even at a concentration of 0.6% w/v (66 mM). A response surface central composite design was used to evaluate the interaction between acetic and lactic acids on the specific growth rate of both yeast strains at 30 degrees C. The data were analysed using the General Linear Models (GLM) procedure. From the analysis, the interaction between acetic acid and lactic acid was statistically significant (P < or = 0.001), i.e., the inhibitory effect of the two acids present together in a medium is highly synergistic.

Effect of lactobacilli on yeast growth, viability and batch and semi-continuous alcoholic fermentation of corn mash.

AIMS: The aim of this study was to evaluate interactions between Saccharomyces cerevisiae and selected strains of lactobacilli regarding cell viabilities, and production of organic acids and ethanol during fermentation. METHODS AND RESULTS: Corn mashes were inoculated with yeasts and selected strains of lactobacilli, and fermented in batch or semi-continuous (cascade) mode. Ethanolic fermentation rates and viabilities of yeast were not affected by lactobacilli unless the mash was pre-cultured with lactobacilli. Then, yeast growth was inhibited and the production of ethanol was reduced by as much as 22%. CONCLUSION: Yeasts inhibited the multiplication of lactobacilli and this resulted in reduced production of acetic and lactic acids. The self-regulating nature of the cascade system allowed the yeast to recover, even when the lactobacilli had a head start, and reduced the size of the population of the contaminating Lactobacillus to a level which had an insignificant effect on fermentation rate or ethanol yield. SIGNIFICANCE AND IMPACT OF THE STUDY: Contamination during fermentation is normally taken care of by the large yeast inoculum, although yeast growth and fermentation rates could be adversely affected by the presence of high numbers of lactobacilli in incoming mash or in transfer lines.

Urea hydrogen peroxide reduces the numbers of lactobacilli, nourishes yeast, and leaves no residues in the ethanol fermentation.

Urea hydrogen peroxide (UHP) at a concentration of 30 to 32 mmol/liter reduced the numbers of five Lactobacillus spp. (Lactobacillus plantarum, L. paracasei, Lactobacillus sp. strain 3, L. rhamnosus, and L. fermentum) from approximately 10(7) to approximately 10(2) CFU/ml in a 2-h preincubation at 30 degrees C of normal-gravity wheat mash at approximately 21 g of dissolved solids per ml containing normal levels of suspended grain particles. Fermentation was completed 36 h after inoculation of Saccharomyces cerevisiae in the presence of UHP, even when wheat mash was deliberately contaminated (infected) with L. paracasei at approximately 10(7) CFU/ml. There were no significant differences in the maximum ethanol produced between treatments when urea hydrogen peroxide was used to kill the bacteria and controls (in which no bacteria were added). However, the presence of L. paracasei at approximately 10(7) CFU/ml without added agent resulted in a 5.84% reduction in the maximum ethanol produced compared to the control. The bactericidal activity of UHP is greatly affected by the presence of particulate matter. In fact, only 2 mmol of urea hydrogen peroxide per liter was required for disinfection when mashes had little or no particulate matter present. No significant differences were observed in the decomposition of hydrogen peroxide in normal-gravity wheat mash at 30 degrees C whether the bactericidal agent was added as H(2)O(2) or as urea hydrogen peroxide. NADH peroxidase activity (involved in degrading H(2)O(2)) increased significantly (P = 0.05) in the presence of 0.75 mM hydrogen peroxide (sublethal level) in all five strains of lactobacilli tested but did not persist in cells regrown in the absence of H(2)O(2). H(2)O(2)-resistant mutants were not expected or found when lethal levels of H(2)O(2) or UHP were used. Contaminating lactobacilli can be effectively managed by UHP, a compound which when used at ca. 30 mmol/liter happens to provide near-optimum levels of assimilable nitrogen and oxygen that aid in vigorous fermentation performance by yeast.

Effects of lactobacilli on yeast-catalyzed ethanol fermentations.

Normal-gravity (22 to 24 degrees Plato) wheat mashes were inoculated with five industrially important strains of lactobacilli at approximately 10(5), approximately 10(6), approximately 10(7), approximately 10(8), and approximately 10(9) CFU/ml in order to study the effects of the lactobacilli on yeast growth and ethanol productivity. Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus #3, Lactobacillus rhamnosus, and Lactobacillus fermentum were used. Controls with yeast cells but no bacterial inoculation and additional treatments with bacteria alone inoculated at approximately 10(7) CFU/ml of mash were included. Decreased ethanol yields were due to the diversion of carbohydrates for bacterial growth and the production of lactic acid. As higher numbers of the bacteria were produced (depending on the strain), 1 to 1.5% (wt/vol) lactic acid resulted in the case of homofermentative organisms. L. fermentum, a heterofermentative organism, produced only 0.5% (wt/vol) lactic acid. When L. plantarum, L. rhamnosus, and L. fermentum were inoculated at approximately 10(6) CFU/ml, an approximately 2% decrease in the final ethanol concentration was observed. Smaller initial numbers (only 10(5) CFU/ml) of L. paracasei or Lactobacillus #3 were sufficient to cause more than 2% decreases in the final ethanol concentrations measured compared to the control. Such effects after an inoculation of only 10(5) CFU/ml may have been due to the higher tolerance to ethanol of the latter two bacteria, to the more rapid adaptation (shorter lag phase) of these two industrial organisms to fermentation conditions, and/or to their more rapid growth and metabolism. When up to 10(9) CFU of bacteria/ml was present in mash, approximately 3.8 to 7.6% reductions in ethanol concentration occurred depending on the strain. Production of lactic acid and a suspected competition with yeast cells for essential growth factors in the fermenting medium were the major reasons for reductions in yeast growth and final ethanol yield when lactic acid bacteria were present.

Use of virginiamycin to control the growth of lactic acid bacteria during alcohol fermentation.

The antibiotic virginiamycin was investigated for its effects on growth and lactic acid production by seven strains of lactobacilli during the alcoholic fermentation of wheat mash by yeast. The lowest concentration of virginiamycin tested (0.5 mg Lactrol kg-1 mash), was effective against most of the lactic acid bacteria under study, but Lactobacillus plantarum was not significantly inhibited at this concentration. The use of virginiamycin prevented or reduced potential yield losses of up to 11% of the produced ethanol due to the growth and metabolism of lactobacilli. However, when the same concentration of virginiamycin was added to mash not inoculated with yeast, Lactobacillus rhamnosus and L. paracasei grew after an extensive lag of 48 h and L. plantarum grew after a similar lag even in the presence of 2 mg virginiamycin kg-1 mash. Results showed a variation in sensitivity to virginiamycin between the different strains tested and also a possible reduction in effectiveness of virginiamycin over prolonged incubation in wheat mash, especially in the absence of yeast.

Effects of particulate materials and osmoprotectants on very-high-gravity ethanolic fermentation by Saccharomyces cerevisiae.

The effects of osmoprotectants (such as glycine betaine and proline) and particulate materials on the fermentation of very high concentrations of glucose by the brewing strain Saccharomyces cerevisiae (uvarum) NCYC 1324 were studied. The yeast growing at 20 degrees C consumed only 15 g of the sugar per 100 ml from a minimal medium which initially contained 35% (wt/vol) glucose. Supplementing the medium with a mixture of glycine betaine, glycine, and proline increased the amount of sugar fermented to 30.5 g/100 ml. With such supplementation, the viability of the yeast cells was maintained above 80% throughout the fermentation, while it dropped to less than 12% in the unsupplemented controls. Among single additives, glycine was more effective than proline or glycine betaine. On incubating the cultures for 10 days, the viability decreased to only 55% with glycine, while it dropped to 36 and 27%, respectively, with glycine betaine and proline. It is suggested that glycine and proline, known to be poor nitrogen sources for growth, may serve directly or indirectly as osmoprotectants. Nutrients such as tryptone, yeast extract, and a mixture of purine and pyrimidine bases increased the sugar uptake and ethanol production but did not allow the population to maintain the high level of cell viability. While only 43% of the sugar was fermented in unsupplemented medium, the presence of particulate materials such as wheat bran, wheat mash insolubles, alumina, and soy flour increased sugar utilization to 68, 75, 81, and 82%, respectively.

Lysine inhibition of Saccharomyces cerevisiae: role of repressible L-lysine ε-aminotransferase.

Lysine added to grain mashes under nitrogen-limiting conditions (as in most industrial fermentations) inhibited growth of Saccharomyces cerevisiae. This inhibition was relieved by raising the assimilable nitrogen content. Lysine-induced inhibition is not mediated through accumulation of α-oxoadipic acid, an intermediate of lysine metabolism which accumulates by a back up of intermediates in de novo synthesis. Lysine degradation is regulated by the synthesis of L-lysine ε-aminotransferase, an enzyme that catalyses the first step in one of three possible routes of lysine degradation (not previously reported in S. cerevisiae). Synthesis is repressed under nitrogenlimiting conditions, but derepressed when excess assimilable nitrogen is available. Derepression results in degradation of lysine and decreases inhibitory effects on growth. The toxic compound appears to be lysine itself.

Relationship of low lysine and high arginine concentrations to efficient ethanolic fermentation of wheat mash.

Very high gravity wheat mashes containing 20 or more grams of carbohydrates per 100 mL were fermented completely by Saccharomyces cerevisiae, even though these mashes contained low amounts of assimilable nitrogen. Supplementation of wheat mashes with various amino acids or with yeast extract, urea, or ammonium sulfate reduced the fermentation time. However, lysine or glycine added as single supplements, inhibited yeast growth and fermentation. With lysine, yeast growth was severely inhibited, and a loss of cell viability as high as 80% was seen. Partial or complete reversal of lysine-induced inhibition was achieved by the addition of a number of nitrogen sources. All nitrogen sources that relieved lysine-induced inhibition of yeast growth also promoted uptake of lysine and restored cell viability to the level observed in the control. They also increased the rate of fermentation. Experiments with minimal media showed that for lysine to be inhibitory to yeast growth, assimilable nitrogen in the medium must be in growth-limiting concentrations or totally absent. In the presence of excess nitrogen, lysine stimulated yeast growth and fermentation. Results indicate that supplementing wheat mash with other nitrogen sources increases the rate of fermentation not only by providing extra nitrogen but also by reducing or eliminating the inhibitory effect of lysine on yeast growth.

Comparison of enzyme immunoassay and fluorescence polarization immunoassay as techniques for measuring anticonvulsant drugs on the same analytical instrument.

We have applied kits for enzyme immunoassay and fluorescence polarization immunoassay of anticonvulsant drugs to the same centrifugal analyser. There was a good correlation between the two techniques for the assay of phenytoin, carbamazepine, and phenobarbitone. Within- and between-batch reproducibility was also comparable but only the fluorescence polarization system allowed the use of stored calibration curves. The ability to use stored curves may be particularly advantageous to laboratories required to run a large number of stat assays or who are handling low workloads of particular analytes.

Fuel alcohol production: effects of free amino nitrogen on fermentation of very-high-gravity wheat mashes.

Although wheat mashes contain only growth-limiting amounts of free amino nitrogen, fermentations by active dry yeast (Saccharomyces cerevisiae) were completed (all fermentable sugars consumed) in 8 days at 20 degrees C even when the mash contained 35 g of dissolved solids per 100 ml. Supplementing wheat mashes with yeast extract, Casamino Acids, or a single amino acid such as glutamic acid stimulated growth of the yeast and reduced the fermentation time. With 0.9% yeast extract as the supplement, the fermentation time was reduced from 8 to 3 days, and a final ethanol yield of 17.1% (vol/vol) was achieved. Free amino nitrogen derived in situ through the hydrolysis of wheat proteins by a protease could substitute for the exogenous nitrogen source. Studies indicated, however, that exogenously added glycine (although readily taken up by the yeast) reduced the cell yield and prolonged the fermentation time. The results suggested that there are qualitative differences among amino acids with regard to their suitability to serve as nitrogen sources for the growth of yeast. The complete utilization of carbohydrates in wheat mashes containing very little free amino nitrogen presumably resulted because they had the "right" kind of amino acids.

Effect of pH on the rate of Candida utilis cell cycle initiation.

The rate of cell cycle initiation (as determined by the rate of bud emergence) in yeast Candida utilis under ammonium-limited phased cultivation was dependent on the pH at which the yeast was grown.

Neuromuscular drug interactions of clinical importance.

The addition of marginally effective concentrations of d-tubocurarine (d-Tc), neomycin, or polymyxin B to the organ bath of rat phrenic nerve-hemidiaphragm preparations significantly (p < 0.05 to 0.001) increased the neuromuscular (NM) blocking effect of lidocaine. When both d-Tc and neomycin or polymyxin B were added the increase of the NM effect of lidocaine was even greater (p < 0.001). Washout re-established NM transmission. The NM block produced by combinations of d-Tc, neomycin, or polymyxin and lidocaine could be reversed partially by Ca2+ or neostigmine, and completely by 4-aminopyridine. The block caused by d-Tc and lidocaine was partially antagonized by neostigmine or 4-aminopyridine., The neomycin-lidocaine or the polymyxin B-lidocaine block, however, was not antagonized by thse compounds. The concentrations of d-Tc, antibiotics, and lidocaine that caused significant block in this in vitro preparation may be present at the NM junction of patients, who in the perioperative period had received combinations of therapeutic doses of d-Tc, neomycin, other aminoglycosides, or polymyxin B and lidocaine. This may cause impairment of spontaneous respiration requiring assisted ventilation.