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A weighed 3-day diet record for postmenopausal Caucasian women indicatesthe dietary consumption of vitamin K linked to the phylloquinone status applied as an identifier of vitamin K level. The amount of phylloquinone intake and the plasma phylloquinone levels are related. Five days are essential to detect normal phylloquinone intake. The ratio of intra- to interindividual discrimination in phylloquinone usage is 2.6.

BACKGROUND: The putative beneficial effects of an increased consumption of fruit and vegetables have been associated with antioxidant nutrients. However, the effect of fruit and vegetable consumption on the overall antioxidant status in humans is unclear. OBJECTIVE: The objective of this study was to investigate whether a diet rich in fruit and vegetables would affect the antioxidant capacity of human plasma. DESIGN: Thirty-six healthy nonsmokers resided in a metabolic research unit and consumed 2 sets of controlled diets. Diet A contained 10 servings of fruit and vegetables each day for 15 d. Diet B was the same as diet A, except diet B also provided 2 servings of broccoli each day on days 6-10. There was a free-living period of a minimum of 6 wk between the 2 experiments using either diet A or diet B. Fasting plasma antioxidant capacity, measured as oxygen radical absorbance capacity (ORAC), and alpha-tocopherol concentrations were determined on days 1, 6, 11, and 16. RESULTS: The fasting baseline plasma ORAC of these subjects was significantly correlated with their estimated daily intake of total antioxidants from fruit and vegetables during the previous year. Plasma ORAC of these subjects was significantly increased by both diets A and B. This increase in ORAC could not be explained by the increase in the plasma alpha-tocopherol concentration. CONCLUSION: Increased consumption of fruit and vegetables can increase the plasma antioxidant capacity in humans. Copyright (c) 1998 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Biochemical indexes for assessing vitamin K nutritional status were evaluated in 263 healthy subjects (127 males, 136 females) aged 18-85 y. The influences of aging (stratified by decade), menopause, and sex were examined. Total, carboxylated, and undercarboxylated osteocalcin concentrations were affected by sex and aging with increases in the sixth decade in women attributed to menopause. Aging effects in the women and sex differences were eliminated when undercarboxylated osteocalcin was expressed as a percentage of the total. Plasma phylloquinone and undercarboxylated prothrombin (PIVKA-II) concentrations varied little with aging with the exception of lower concentrations of phylloquinone in women in their third decade compared with other ages and higher concentrations of PIVKA-II in younger males compared with younger females. Urinary gamma-carboxyglutamic acid (Gla)-creatinine excretion ratios increased significantly with age in both males (r = 0.68, P < 0.001) and females (r = 0.63, P < 0.001) with values 20% higher in the females on average over the entire age span. The undercarboxylated osteocalcin concentration, shown previously to be responsive to depletion and repletion of phylloquinone, was compared with the other indexes to determine its reliability as an indicator of vitamin K nutritional status. This measure appears promising because it correlated with plasma PIVKA-II concentrations (r = 0.27, P < 0.001) and with plasma phylloquinone concentrations (r = -0.35, P < 0.001), whereas the agreement between plasma phylloquinone and PIVKA-II concentrations was not as strong (r = -0.15, P < 0.05). (c) 1996 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Background: Laparoscopic approaches to inguinal hernia repair include transabdominal extraperitoneal and transabdominal preperitoneal, both of which are widely performed and employ mesh. Indicators of success for these surgical procedures include incidence of complications, time to return to daily activities, incidence of postoperative chronic pain, and the long-term postoperative patient satisfaction., Objective: This study aimed to evaluate and compare long-term postoperative incidence of chronic pain and overall quality of life among patients undergoing transabdominal extraperitoneal or transabdominal preperitoneal inguinal hernia repair., Methods: This was a retrospective cross-sectional study. Medical records were analyzed, and the SF-36 questionnaire and Visual Analog Scale were applied to assess quality of life and chronic pain in patients undergoing laparoscopic inguinal hernia repair between January 2017 and February 2021., Results: A total of 167 patients status post laparoscopic inguinal hernia repair, who were 3 months postoperatively or longer, were included in the study. Among the early complications seen, seroma was most common in the transabdominal preperitoneal group (p=0.04). Subsequently, 40 of the initial 167 patients answered to the survey instrument (SF-36 and Visual Analog Scale). Mean patient-reported pain (Visual Analog Scale score) was statistically similar between groups, with 1.29 for transabdominal preperitoneal and 1.68 for transabdominal extraperitoneal (p=0.92). In the domains evaluated by the SF-36, there was no significant difference between the samples., Conclusion: Both transabdominal extraperitoneal and transabdominal preperitoneal techniques for hernia repair have similar results in the late postoperative period regarding quality of life and prevalence of chronic pain. They are also comparable in terms of major early postoperative complications, except for seroma, with a higher incidence in patients undergoing transabdominal preperitoneal.

Background: Laparoscopic conversion of Nissen Fundoplication to Roux-en-Y gastric bypass (RYGB) is a complex procedure due to increased operative time, morbidity, and length of hospital stay (LOS). In this study, a new simplified technique avoiding the total dismantling of the previous Nissen repair to construct the gastric pouch, the so-called hug technique is presented for the conversion of Nissen fundoplication to RYGB., Methods: The present study is a prospective single-center clinical series reporting on the feasibility and safety of the "hug" technique for the creation of laparoscopic RYGB. The major innovation of this approach is the fact that the posterior part of the fundoplication wrap is left in place without further dissection or manipulation. The anterior part is stapled and remains attached to the excluded stomach. Prospective data on intraoperative and postoperative morbidity and bariatric outcomes were collected., Results: A total of 44 consecutive patients with a mean body mass index (BMI) of 43.7 kg/m 2 (SD = 4.0, range = 35.6-52.0) underwent the "hug" procedure between 2004 and 2015. Mean operative time was 72 min (58-105 min). Morbidity was 4.5%, with no mortality. For patients with follow-up at 3 years, the percentage of total body weight loss (%TBWL) was 32.5%; the excess weight loss (EWL) was 64.2%., Conclusion: In contrast to current other techniques of bariatric surgery for patients having previously undergone a Nissen fundoplication, the "hug" procedure to create an RYGB is safe and simple to perform. This technique avoids the deconstruction of the previous repair and is still maintaining anti-reflux anatomy. Nevertheless, there is a need for further studies to evaluate the long-term outcomes of the procedure.

Unlabelled: Abdominoplasty is a very common elective procedure in plastic surgery. Surgical accidents can lead to serious complications that result in an acute surgical abdomen, but in rare cases, an acute surgical abdomen not related to the procedure develops. This report discusses the diagnostic approach for patients with an acute abdomen after abdominoplasty and presents a case of appendicitis in the immediate postoperative period. The importance of postoperative follow-up evaluation by the same surgeon who performed the procedure is discussed as well as the need for adequate general surgery training to obtain the correct diagnosis and perform the urgent operation required to avoid a detrimental outcome., Level of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

In a comparison to the widely used Cronobacter rpoB PCR assay, a highly specific multiplexed PCR assay based on cgcA, a diguanylate cyclase gene, that identified all of the targeted six species among 305 Cronobacter isolates was designed. This assay will be a valuable tool for identifying suspected Cronobacter isolates from food-borne investigations.

Cronobacter (formerly Enterobacter sakazakii) is a recently defined genus consisting of six species, C. sakazakii, C. malonaticus, C. dublinensis, C. muytjensii, C. turicensis, and Cronobacter genomospecies 1. In this study, MboII restriction fragment length polymorphism (RFLP) patterns of O-antigen gene clusters, located between galF and gnd, were used to identify serotypes in Cronobacter spp. Seven O-antigen RFLP clusters were generated, including three C. sakazakii clusters, previously identified as serotypes O1, O2, and O3. The O-antigen regions of six strains with unique RFLP patterns, including two C. sakazakii strains, two C. malonaticus strains, one C. turicensis strain, and one C. muytjensii strain, revealed three O-antigen gene clusters shared among Cronobacter species. PCR assays were developed, targeting the wzx O-antigen polymerase gene, and used to screen 231 Cronobacter strains to determine the frequency of these newly identified serotypes.

Objective: The aim of this study is to compare data of patients submitted to appendectomy for acute appendicitis at a public hospital and at a private hospital., Methods: A total of 200 medical records of patients submitted to appendectomy for acute appendicitis at a public hospital (n=100) and at a private hospital (n=100), was reviewed retrospectively., Results: Mean age and gender distribution were similar for patients of both hospitals. More patients had been previously evaluated by other physicians in the group of the public hospital (n=85) than of the private hospital (n=13) (p< 0.0001). Ultrasonography was performed more frequently on patients of the public hospital (n=56) than of the private hospital (n=30) (p=0.0002). Length of hospital stay was longer at the public hospital (3.5 ± 2.8 days) than at the private hospital (2.5 ± 1.7 days) (p=0.0024). Postoperative complications were more frequent at the public hospital (n=36) than at the private hospital (n=20) (p<0.0117). Time to resume routine activities was longer for the public hospital (33.2 ± 8.3 days) than for the private hospital (16.4 ± 5.2 days) (p<0.0001). Multivariate logistic-regression analysis showed that the estimated probability of complicated appendicitis increased with the time interval between onset of symptoms and appendectomy (p<0.001). Independent risk factor associated with complicated appendicitis was the time interval between onset of symptoms and appendectomy (odds ratio 41.65, 95% CI {confidence interval} 2.90-597.49, p<0.0001) at the public hospital. There was no independent risk factor associated with complicated appendicitis at the private hospital., Conclusion: There are important differences between public and private hospitals in the diagnosis and outcomes of patients with acute appendicitis submitted to appendectomy.

Empirical studies of sexual selection typically focus on one of the two mechanisms of sexual selection without integrating these into a description of total sexual selection, or study total sexual selection without quantifying the contributions of all of the mechanisms of sexual selection. However, this can provide an incomplete or misleading view of how sexually selected traits evolve if the mechanisms of sexual selection are opposing or differ in form. Here, we take a two-fold approach to advocate a direction for future studies of sexual selection. We first show how a quantitative partitioning and examination of sexual selection mechanisms can inform by identifying illustrative studies that describe both male-male competition and female mate choice acting on the same trait. In our sample, the most common trait where this occurred was body size, and selection was typically linear. We found that male-male competition and female mate choice can be reinforcing or opposing, although the former is most common in the literature. The mechanisms of sexual selection can occur simultaneously or sequentially, and we found they were more likely to be opposing when the mechanisms operated sequentially. The degree and timing that these mechanisms interact have important implications for the operation of sexual selection and needs to be considered in designing studies. Our examples highlight where empirical data are needed. We especially lack standardized measures of the form and strength of selection imposed by each mechanism of sexual selection and how they combine to determine total sexual selection. Secondly, using quantitative genetic principles, we outline how the selection imposed by individual mechanisms can be measured and combined to estimate the total strength and form of sexual selection. We discuss the evolutionary consequences of combining the mechanisms of sexual selection and interpreting total sexual selection. We suggest how this approach may result in empirical progress in the field of sexual selection.

Background: The influence of hypothyroidism in liver regeneration has been a controversial opinions., Purpose: The aim of this study is to identify the relationship between hypothyroidism and liver regeneration in rats., Methods: Forty male Wistar rats divided into two groups of 20 specimens each. One group (C) consisted of euthyroid rats, and the other (H) of hypothyroid rats. All the animals were anesthetized with xylazine and ketamine and subjected to a longitudinal incision in the anterior cervical region. The thyroid was completely resected in group H and left intact in group C. Ten days after the first surgery, both groups of rats were weighed and submitted to partial hepatectomy, in which the left lateral and median lobes were resected and weighed. Examinations were carried out after 24 hours and, on day 7, using 3 methods: KWON et al.'s formula to identify increase in volume; mitotic figure count in five fields; and the percentage of PCNA-positive nuclei in five fields., Results: Using KWON's formula, the regeneration rate for Group C after 24 hours was 58.49% whereas that for Group H was 50.42% (p=0.0165). After 7 days, the regeneration rate for Group C was 93.04% and Group H 93.74% (p=0.2165). The average number of mitotic figures after 24 hours was 14 +/- 1.5 for Group C and 9.8 +/- 2.2 for Group H (p=0,00016). After 7 days the corresponding figures were 5.4 +/-1.1 and 5.1+/- 1.2 (p=0,6343). The average number of PCNA-positive nuclei after 24 hours was 13.55+/- 3.84 in Group C and 7.7 +/- 2.11 in Group H (p =0,0006)). The corresponding figures after 7 days were 3.5 +/- 2.39 for Group C and 4.11 +/-1.90 for Group H (p>0.05)., Conclusion: We conclude that hypothyroidism in rats causes a delay in hepatic regeneration in the first 24 hours, but that after seven days the rate of regeneration is equal to that in euthyroid rats.

We investigated the association of vitamin K status with warfarin sensitivity among 40 orthopaedic patients beginning perioperative algorithm-dosed warfarin. Baseline vitamin K status was assessed using plasma vitamin K-1 and vitamin K-1 2,3 epoxide concentrations, and a questionnaire-based estimation of usual vitamin K intake. Warfarin sensitivity was assessed as the increase in the International Normalized Ratio (INR) after two doses of 5 mg of warfarin and as the 4-d accumulation of under-gamma-carboxylated prothrombin (PIVKA-II), adjusted for warfarin dose requirement. Multivariate models were used to assess vitamin K variables as predictors of warfarin sensitivity. The mean INR increase was 0.53 U and the mean PIVKA-II increase was 771 ng/ml/mg warfarin. Demographic factors were not associated with warfarin response. For each 1 standard deviation (SD) lower value of plasma vitamin K-1, but not the other vitamin K variables, the INR rose 0.24 U (P < or = 0.01). A higher usual vitamin K intake and plasma vitamin K-1, and lower plasma vitamin K-1 2,3 epoxide, were all associated with a lower PIVKA-II increase over 4 d. Respective differences in PIVKA-II accumulation per SD increase of each variable were -165, -218 and 236 ng/ml/mg warfarin (all P < or = 0.05). We concluded that dietary and biochemical measures of vitamin K status were associated with early warfarin sensitivity.

The potential mechanism underlying the rapid response to vitamin K replacement in acquired deficiency states is incompletely understood. To examine vitamin K metabolism, a 10-year-old boy with autoimmune enteropathy on oral vitamin K supplementation, who presented with profuse nosebleeds and calf tenderness, was evaluated. Laboratory analyses were consistent with severe vitamin K deficiency: vitamin K dependent protein (VKDP) levels < 5%, normal vitamin K epoxide level and depressed total prothrombin antigen (carboxylated and undercarboxyated forms). Intramuscular vitamin K (10 mg) was administered. Nine hours following therapy, VKDP levels corrected completely. Total prothrombin antigen increased indicating new prothrombin synthesis. However, the increase in the prothrombin-clotting assay far exceeded the increase in total prothrombin, supporting storage of undercarboxylated prothrombin in vitamin K deficiency states, with carboxylation and secretion after vitamin K replacement. Although this mechanism is known to occur in rodents, it has not been reported in humans. Our findings suggest a new potential mechanism of prothrombin metabolism in humans.

Phylloquinone and ten menaquinones (MK-1-MK-10) were measured in liver and eight extrahepatic tissues from male and female rats at 3, 12 and 24 mo of age. Phylloquinone and menaquinones showed characteristic tissue distribution. In liver, all 11 vitamers of vitamin K assayed were present in varying concentrations with phylloquinone and MK-6 the major forms. The only forms of vitamin K found in extrahepatic tissues were phylloquinone, MK-4 and MK-6. Brain contained only MK-4 and traces of phylloquinone. No significant gender difference was observed for phylloquinone except in heart at 3 mo of age (P

Gender differences in relation to vitamin K were investigated in the rat. Hepatic phylloquinone and menaquinone (MK-1 to MK-10) concentrations, gamma-carboxyglutamic acid (Gla) excretion, plasma phylloquinone and percent prothrombin were measured in male and female rats on a chow diet (24.5 ng phylloquinone and 8.8 microgram menadione), and on phylloquinone-deficient and -supplemented purified diets (0.38 and 1400 ng phylloquinone/g, respectively). Mean hepatic phylloquinone concentrations varied with dietary intake and ranged from 6.8+/-9.0 pmol/g in the deficient male, to 171. 1+/-56.9 pmol/g in the supplemented female. Menaquinones accounted for a large proportion of total vitamin K in the liver of males and females with MK-4, MK-6, and MK-10 present in highest concentrations. On the chow and supplemented diets, females had significantly higher MK-4, MK-6, and MK-10 concentrations in their livers (P<0.05). On the phylloquinone-deficient diet (-K1), hepatic phylloquinone, MK-4, and to a lesser extent MK-6 (but not MK-10) were significantly reduced (P<0.05). In the phylloquinone-supplemented male and female groups, which did not receive menadione during the experimental period, MK-4 increased above that in the chow groups suggesting synthesis of MK-4 from phylloquinone which was statistically significant in the female (P<0.01). A significant gender difference (P<0.05) was also observed for urinary Gla excretion with less Gla excreted by the females indicating that females may require less dietary phylloquinone than males of the same body weight.

Subjects taking a hydrogen pump blocking agent (omeprazole) develop bacterial overgrowth of the small intestine. We tested the hypothesis that this bacterial overgrowth produces menaquinones, which would meet the vitamin requirement in situations of vitamin K deficiency. In a crossover-type design, 13 healthy volunteers eating a phylloquinone-restricted diet for 35 d were randomly assigned to take omeprazole during the first period of study or starting on day 15 until the end of the study. Coagulation times, serum osteocalcin [total osteocalcin and undercarboxylated osteocalcin (ucOC)], plasma phylloquinone, urinary gamma-carboxyglutamic acid, and plasma undercarboxylated prothrombin (PIVKA-II) were measured. Plasma phylloquinone concentrations declined 82% with dietary phylloquinone restriction (P < 0.05) and were not significantly different in the period when the diet was combined with omeprazole treatment (P > 0.05). The mean value for PIVKA-II during the phylloquinone-restricted diet significantly increased 5.7-fold from baseline (P < 0.05); however, the combination of omeprazole treatment and the phylloquinone-restricted diet significantly reduced PIVKA-II values by 21% (P < 0.05) compared with the diet period alone. There were no alterations in total or percentage ucOC concentrations during the phylloquinone-restricted diet or during the period of diet plus omeprazole treatment. Our data support the hypothesis that bacterial overgrowth results in the synthesis and absorption of menaquinones. These menaquinones contribute to vitamin K nutriture during dietary phylloquinone restriction, but not enough to restore normal vitamin K status.

The purpose of this study was to characterize the absorption and transport of phylloquinone (vitamin K1) by plasma lipoproteins. Twenty-six healthy subjects (11 men and 15 women) aged 20-78 y received phylloquinone in the amount of either 1.43 or 50 microg/kg body wt orally with a fat-rich meal containing 1.0 g/kg body wt of fat, carbohydrate, and protein and 7.0 mg cholesterol/kg body wt. Blood was obtained at baseline (0 h) and 3, 6, 9, and 12 h after the meal for the measurement of plasma lipid and phylloquinone concentrations in plasma and lipoprotein subfractions. In both groups of subjects, triacylglycerol concentrations peaked after 3 h in plasma and in the triacylglycerol-rich lipoprotein fraction, composed of chylomicrons and VLDLs. Plasma phylloquinone concentrations peaked at 6 h. At baseline and during the postprandial phase, > 53% of plasma phylloquinone was carried by the triacylglycerol-rich lipoprotein fraction. In 9 of the 11 subjects supplemented with 50 microg phylloquinone/kg, plasma lipoproteins were isolated by sequential ultracentrifugation. In these subjects the fraction of plasma phylloquinone carried by LDLs and by HDLs increased progressively from 3% and 4% at 3 h to 14% and 11% at 12 h, respectively. Our data indicate that whereas triacylglycerol-rich lipoproteins are the major carriers of phylloquinone, LDL and HDL may carry small fractions of this vitamin.

A diurnal variation exists in blood levels of the vitamin K-dependent bone protein osteocalcin. However, it is not known whether the carboxylated and undercarboxylated constituents of osteocalcin also vary. Therefore, osteocalcin and undercarboxylated osteocalcin were measured in specimens collected every 4 hours over a 24-hour period in nine healthy subjects (five males, four females) ages 20-33 years who were consuming a mixed diet containing 100 microg of phylloquinone. Osteocalcin and undercarboxylated osteocalcin were measured by radioimmunoassay (RIA) before and after treatment with barium sulfate. Although the percent undercarboxylated osteocalcin did not change, a diurnal variation was observed in total osteocalcin, carboxylated osteocalcin, and undercarboxylated osteocalcin, with peak concentrations at 4 a.m. and the lowest concentrations between 12 p.m. and 4 p.m. The difference between the total osteocalcin peak and trough concentrations averaged 28 +/- 7 (SEM)%. There were no gender differences in these rhythms. The effect of dietary phylloquinone as a modulator of these rhythms was evaluated in a randomized study by increasing phylloquinone intake to 420 microg/day with fortified corn oil, split between the lunch and dinner meals. Total and carboxylated osteocalcin fluctuations and concentrations were not affected by the dietary treatment. The diurnal variation in undercarboxylated osteocalcin was abolished with supplementation and concentrations at 8 a.m. (14 hours following supplementation) (2.3 +/- 0.2 ng/ml) were significantly lower than the unsupplemented levels (2.7 +/- 0.2 ng/mL, P = 0.006). The percentage of undercarboxylated osteocalcin was similarly decreased after supplementation (19.7 +/- 1.3%) in relation to the mixed diet cycle (24.2 +/- 1.6%, P = 0.006) at 8 a.m. on the second day. Dietary supplementation induced a fluctuation in percentage undercarboxylated osteocalcin with a decline in levels starting at approximately 12 a.m. Therefore, additional dietary phylloquinone does not appear to modulate the total osteocalcin diurnal rhythm, but can influence its undercarboxylated component.

Atrophic gastritis patients have intestinal bacterial overgrowth which could produce menaquinones. The aim of this study was to evaluate the interaction between a diet low in phylloquinone and minidoses of warfarin in subjects with and without bacterial overgrowth. Subjects with atrophic gastritis (indicated by serum pepsinogen ratio) and healthy volunteers were studied while fed a restrictive phylloquinone diet and while receiving a minidose of warfarin. Coagulation times, serum osteocalcin, serum undercarboxylated osteocalcin, plasma phylloquinone, plasma K-epoxide, plasma undercarboxylated prothrombin (PIVKA)-II and urinary gamma-carboxyglutamic acid (Gla) were measured. At baseline, there were no differences between groups for any variable measured. Comparisons between baseline and post intervention in both groups, showed significant increases in circulating levels of K-epoxide, PIVKA II and undercarboxylated osteocalcin. However, no differences were observed when comparisons were made between groups. Our data do not support the hypothesis that bacterial synthesis of menaquinones in patients with bacterial overgrowth due to atrophic gastritis confers considerable resistance to the effect of warfarin.

Objective: To measure directly plasma vitamin K1 in patients with primary biliary cirrhosis (PBC) and to examine the relationship between vitamin K1 level, prothrombin time, other fat-soluble vitamin levels, and severity of cholestasis., Methods: We directly measured levels of vitamin K1 (phylloquinone) in the plasma of 77 patients with PBC using reverse-phase high-performance liquid chromatography, along with serum levels of vitamins A, E, and 25-OH vitamin D., Results: Median plasma vitamin K1 level was significantly lower in PBC patients compared with 255 normal subjects (0.65 nmol/L; range, 0.05-4.13, vs 0.95 nmol/L; range, 0.2-4.92; p < 0.0001). Of 77 PBC patients, 18 (23%) patients had levels below the normal range for plasma vitamin K1 (<0.3 nmol/L). Only 1 of the 18 patients with decreased vitamin K1 had a prolonged prothrombin time. There was no correlation between vitamin K1 level and prothrombin time in the PBC patients (p = 0.75); there was also no difference in prothrombin time between PBC patients with low vitamin K1 level and PBC patients with normal vitamin K1 level (10.3 vs 10.0 seconds; p = 0.28). PBC patients with decreased vitamin K1 levels had significantly lower vitamin A and vitamin E levels, and significantly higher serum bilirubin levels than those with normal vitamin K1 levels., Conclusion: Decreased plasma vitamin K1 level is common in PBC, and is associated with decreased serum levels of vitamins A and E. However, the majority of PBC patients with decreased plasma vitamin K1 levels have normal prothrombin times. Although the prothrombin time is an insensitive marker of vitamin K1 status in PBC patients, clinically important vitamin K deficiency seems uncommon.

Background: Patients with cystic fibrosis are at risk for impaired vitamin K status due to fat malabsorption from pancreatic insufficiency. This study was designed to assess vitamin K status and measure the effect of vitamin K1 supplementation in cystic fibrosis patients., Methods: Eighteen outpatients participated in a crossover study to determine the effect of vitamin K1 (phylloquinone) supplementation. After obtaining initial data, each subject was randomly assigned to either a 4-week study treatment of 5 mg oral vitamin K1 supplementation per week, or no supplementation and then crossed over to the other treatment for a second 4 week period. Plasma, serum and urine samples were collected and analyzed pre-study and at the end of each study period., Results: The mean concentration of plasma vitamin K1 for the supplemented group was significantly higher than the unsupplemented group, [0.34 nmol/L and 0.21 nmol/L, respectively (p < 0.05)]. The percent of undercarboxylated osteocalcin increased on supplementation from 17% to 31%, (p < 0.005). Prothrombin induced in vitamin K absence (PIVKA-II) increased on supplementation from 5 ng/mL to 22 ng/mL, (p < 0.005). The ratio of urinary gamma-carboxyglutamic acid/creatinine was similar for both study periods., Conclusions: In contrast to other studies in cystic fibrosis, this study demonstrated a need for vitamin K1 supplementation. The carboxylation state of osteocalcin and PIVKA-II were the most sensitive indices of changes in vitamin K1 status. Although the 5 mg vitamin K1/week dose improved these vitamin K parameters, normal levels were not achieved.

Dietary intakes of retinol equivalents, alpha-tocopherol equivalents, vitamin D and phylloquinone were estimated from three sets of 4-d weighed diet records and compared to three corresponding fasting plasma concentrations of retinol, 25-hydroxyvitamin D, alpha-tocopherol, and phylloquinone measured in 34 healthy adults over 20 wk. The magnitude of the correlation between dietary vitamin intake and its corresponding biochemical measure is in part determined by the reproducibility of each of the measures, so within-to-between subject variance ratios were calculated for both dietary intakes and plasma concentrations. Phylloquinone was the only fat-soluble vitamin with a significant correlation between dietary intake and fasting plasma concentration (r = 0.51, P = 0.004). This correlation improved with an increase in both the number of independent diet records and independent plasma measures. Of the dietary intake measures, all the fat-soluble vitamins had greater within than between subject variance, with the highest measured for phylloquinone (6.86:1). Of the plasma measures, only phylloquinone had a within-to-between subject variance ratio greater than one (5.36:1). Comparisons across age and sex for dietary intake and plasma concentrations differed in pattern among the fat-soluble vitamins.

Case reports cited in Medline or Biological Abstracts (1966-1996) were reviewed to evaluate the impact of vitamin K1 dietary intake on the stability of anticoagulant control in patients using coumarin derivatives. Reported nutrient-drug interactions cannot always be explained by the vitamin K1 content of the food items. However, metabolic data indicate that a consistent dietary intake of vitamin K is important to attain a daily equilibrium in vitamin K status. We report a diet that provides a stable intake of vitamin K1 equivalent to the current U.S. Recommended Dietary Allowance, using food composition data derived from high-performance liquid chromatography. Inconsistencies in the published literature indicate that prospective clinical studies should be undertaken to clarify the putative dietary vitamin K1-coumarin interaction. The dietary guidelines reported here may be used in such studies.

Dihydro-vitamin K1 is a dietary form of vitamin K1 (phylloquinone) produced during the hydrogenation of vegetable oils. To determine if dihydro-vitamin K1 is present in plasma following dietary intake of a hydrogenated fat, eight healthy adults consumed each of two diets containing 30% of calories from fat, of which 20% was either soybean oil or a partially hydrogenated soybean oil-based stick margarine. Of the fats and oils analyzed, dihydro-vitamin K1 was only found in the hydrogenated products. The soybean oil diet contained 180 +/- 12 micrograms (mean +/- SD) of vitamin K1/day and nondetectable levels of dihydro-vitamin K1, whereas the stick margarine diet contained 199 +/- 7 micrograms of vitamin K1/day and 23 +/- 2 micrograms of dihydro-vitamin K1/day. After consuming each diet for five weeks, plasma dihydro-vitamin K1 concentrations were higher (P = 0.002) in all eight subjects when consuming the stick margarine diet (0.56 +/- 0.33 nmol/L) compared to the soybean oil diet (0.12 +/- 0.11 nmol/L). There was no significant change in plasma vitamin K1 concentrations when the two diets were compared. In conclusion, dihydro-vitamin K1 is detectable in plasma following dietary intake of a hydrogenated vitamin K1-rich vegetable oil.

To assess the effect of orlistat on the pharmacokinetics and pharmacodynamics of warfarin, a third-party blind, placebo-controlled, randomized, two-way crossover study was performed in 12 healthy volunteers. Each participant received single 30-mg oral doses of racemic warfarin sodium (Coumadin; DuPont Pharma, Wilmington, DE) administered on the eleventh day of treatment with 120 mg orlistat (treatment A) and placebo (treatment B) three times a day for 16 days; the two treatments were separated by a 3-week washout period. Serial blood samples were collected before and at appropriate intervals after each dose of warfarin to determine plasma concentrations of R-warfarin and S-warfarin and blood prothrombin time (PT) and plasma Factor VII concentration. In addition, serum concentrations of vitamin K1 and its epoxide and of osteocalcin and its undercarboxylated form were measured before breakfast on days -7, 1, 4, 6, and 10. Equivalent results between treatments with orlistat and placebo were found with regard to all pharmacokinetic parameters of R- and S-warfarin (except for time to maximum concentration of R-warfarin). Pharmacodynamic parameters of warfarin (PT and Factor VII) and vitamin K nutritional status parameters (ratios of vitamin K1 to vitamin K1 epoxide and undercarboxylated osteocalcin to osteocalcin) also were unaltered by orlistat. Orlistat administered at doses of 120 mg three times daily did not significantly alter the pharmacokinetics and pharmacodynamics of a single 30-mg oral dose of warfarin in healthy volunteers.

Dihydro-vitamin K1 was recently identified as a dietary form of vitamin K produced during the hydrogenation of vitamin K1-rich vegetable oils. Dihydro-vitamin K1 is absorbed, with measurable levels in human plasma following dietary intake. To determine the primary food sources of dihydro-vitamin K1 in the American diet, 261 foods from the U.S. Food and Drug Administration's (FDA) Total Diet Study (TDS) were analyzed by high-performance liquid chromatography. Of these foods, 36 contained dihydro-vitamin K1. Fast-food items that were otherwise poor sources of vitamin K1, such as french fries and fried chicken, contained appreciable amounts of dihydro-vitamin K1 (36 and 18 micrograms/100 g, respectively). These nutrient values were then applied to the FDA TDS consumption model to determine average dietary intake of dihydro-vitamin K1 in 14 age-gender groups. With the exception of infants, all age-gender groups had estimated mean daily dihydro-vitamin K1 intakes of 12-24 micrograms, compared to mean daily vitamin K1 intakes of 24-86 micrograms. The vitamin K1 and dihydro-vitamin K1 intakes were summed, and the dietary contribution of dihydro-vitamin K1 was expressed as a percentage of total vitamin K intake. Children reported the highest intakes of dihydro-vitamin K1 (30% of total vitamin K intake), followed by a progressive decrease in percentage contribution with age. There are currently no data on the relative bioavailability of dihydro-vitamin K1 but given its abundance in the American diet, this hydrogenated form of vitamin K warrants further investigation.

Prenatal maternal vitamin K1 supplementation to improve the hemostatic status of the fetus may depend upon the route of administration and subsequent presentation at the placental barrier. We investigated intramuscular (IM) vs oral (PO) vitamin K1 supplementation in eight healthy, nonpregnant women of childbearing age. Pharmacokinetics were studied in each subject after a 5 mg IM dose and after a 5 mg oral dose of vitamin K1 approximately one month later. Plasma collected at the peak vitamin K level for each treatment was separated into very low density lipoproteins (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL) and lipoprotein-free fractions by density gradient ultracentrifugation. Vitamin K1 was measured in the plasma and lipoprotein fractions using HPLC. The concentration of vitamin K1 in plasma reached a peak 2 h after an IM dose and remained high throughout the 30 h course of the study. In contrast, the oral dose of vitamin K1 peaked at 4 h and rapidly decreased to near baseline by 18 to 30 h. The distribution of vitamin K1 in the lipid fractions was different for IM compared to PO. The percentage of vitamin K1 in the VLDL fraction at the peak for an oral dose was significantly higher than for an IM dose (80.8% +/- 3.5 vs 10.8% +/- 6.5, p < 0.0001). After the oral absorption stage, the subjects took 5 mg of vitamin K1 orally, once a day, for 12 days. No significant differences were observed for the following coagulation proteins and hemostatic markers measured immediately before and after long-term oral vitamin K supplementation: factor II, factor VII, protein C, and thrombin-antithrombin III complex. In conclusion, physiological processing of supplemented vitamin K1 differs in the IM vs PO routes of administration and 12 days of oral vitamin K1 does not alter the concentration of selected vitamin K-dependent coagulation proteins or thrombin-antithrombin complex generation.

We developed a RIA involving a polyclonal antibody against bovine osteocalcin, which has a carboxy-terminal epitope. Although the antibody recognizes both native and descarboxy osteocalcin, the two forms of osteocalcin were differentiated by adsorption to barium sulfate, taking advantage of the calcium-binding properties of the vitamin K-dependent gla domain. To test the clinical application of undercarboxylated osteocalcin, we examined the effect of minidose warfarin on this measure in nine healthy subjects, ages 60 to 80 years. The percentage of undercarboxylated osteocalcin increased by 170% +/- 36% (mean +/- SE) after 7 days of treatment with warfarin, 1 mg/day. The effectiveness of undercarboxylated osteocalcin as a sensitive measure of vitamin K nutritional status was further established when concentrations dropped to 17% +/- 14% below baseline with 2 days of repletion with vitamin K1, 5 mg/day, during which prothrombin times did not leave the normal range.

Age-adjusted reference ranges for creatinine clearance were determined in 279 women, ages 40-95 years, who were housed in a metabolic research unit and consumed a meat-free diet. Creatinine clearance, but not serum creatinine, declined with age by 0.63 mL/min per 1.73 m2 per year. Serum and urine creatinine concentrations, used to calculate clearances, were analyzed by a kinetic Jaffé procedure. In a subset of 100 subjects, fasting serum creatinine values averaged 8.3 +/- 5.2 (SD) mumol/L higher when measured by the kinetic Jaffé procedure than by an enzymatic method (creatinine PAP). The Cockcroft-Gault formula for estimating creatinine clearance from serum creatinine in women was validated, and the modification factor for the male equation was determined to be 0.84 (95% confidence interval 0.83-0.86) confirming the suggested 15% correction. A prediction formula derived from this population was similar in accuracy to the Cockcroft-Gault formula.

Urine contains inhibitors of calcium oxalate (CaOx) crystal growth. One such inhibitor is nephrocalcin (NC), a glycoprotein which is made in the kidney and contains several residues of gamma-carboxyglutamic acid (Gla) per molecule. The presence of Gla may be important to its ability to inhibit crystal growth. Several studies suggest that vitamin K-dependent proteins may also play a role in renal calcium (Ca) handling, and that vitamin D deficiency may lead to excess urinary Ca loss, but the effect of the vitamin K antagonist warfarin on urinary Ca excretion and CaOx growth inhibition in humans is not known. We studied 11 men while they were taking warfarin for a mean of 252 days, and again a mean of 64 days after its discontinuation. Urinary Ca excretion did not differ between those on or off warfarin, or between those on warfarin and normal controls. The ability of the subjects' urine to inhibit CaOx crystal growth did not differ on or off warfarin, or from that of control urine, and the excretion of immunoreactive NC also did not differ between these groups. NC was found to be responsible for approximately 16% of the CaOx growth inhibition seen. These results do not suggest that vitamin K-dependent proteins play a major role in renal Ca excretion in men, or that interference with vitamin K alters NC excretion or inhibitory activity of the urine.