Minor differences in perceived sheepmeat eating quality scores of Australian, Chinese and American consumers.

Understanding consumer sensory perceptions of sheepmeat is essential for consumer satisfaction post-purchase. Meat Standards Australia (MSA) sensory protocols have been effectively utilised in beef for international consumers however, to date sheepmeat testing is largely limited to Australian consumers. This study measured the sensory responses (liking of odour, tenderness, juiciness, liking of flavour, and overall liking) of 2160 untrained American, Australian and Chinese consumers to grilled longissimus lumborum (LL) and semimembranosus (SM) muscles from 164 lambs and 168 yearlings. Across countries there was no difference in juiciness or overall liking sensory scores. American consumers scored tenderness, flavour and odour slightly higher than Australian consumers, and Chinese consumer scores were lowest. Consistently for all countries, sensory scores were greatest in the LL muscle, in lambs compared to yearlings particularly for the LL, and Merino sired and female lambs. These results indicate that cultural background has minimal impact on sensory perceptions of sheepmeat, and provides valuable information for future eating quality prediction models.

Factors affecting lamb eating quality and the potential for their integration into an MSA sheepmeat grading model.

Major efforts in the sheep industry to control eating quality have resulted in reduced product variability. Yet inconsistent eating quality for consumers remains, due to a degree of inaccurate representation of cut quality. Eating quality defined through a complex interplay of different factors can be predicted for individual cuts, and Meat Standards Australia (MSA) grading schemes have been developed to achieve these defined quality outcomes. This review outlines the justifications to refine the current sheepmeat MSA pathways system to transition into a cuts-based prediction model and details some of the factors affecting sheepmeat eating quality as key factors under consideration into the new model. The development of the new sheepmeat MSA prediction model will allow for more efficient carcass sorting to underpin a value based payment system throughout the supply chain. However it requires the inclusion of individual carcass yield and eating quality measurements (i.e. IMF). Furthermore, the adoption challenges internationally of an MSA like model are discussed.

Impacts on rural livelihoods in Cambodia following adoption of best practice health and husbandry interventions by smallholder cattle farmers.

To better understand how smallholder farmers whom own the majority of Cambodian cattle can contribute to efforts to address food security needs in the Mekong region, a five-year research project investigating methods to improve cattle health and husbandry practices was conducted. Cattle production in Cambodia is constrained by transboundary animal diseases (TADs) including foot-and-mouth disease (FMD) and haemorrhagic septicaemia (HS) plus poor nutrition, reproduction and marketing knowledge. The project worked in six villages in Kandal, Takeo and Kampong Cham province during 2007-12. Farmers from three 'high intervention' (HI) villages incrementally received a participatory extension programme that included FMD and HS vaccination, forage development and husbandry training. Evaluation of project impacts on livelihoods was facilitated by comparison with three 'low intervention' (LI) villages where farmers received vaccinations only. Results of knowledge, attitude and practice (KAP) and socio-economic surveys conducted in 2012 of 120 participating farmers identified that farmer knowledge in the HI project sites exceeded LI sites on the topics of biosecurity, internal parasites, nutrition and reproduction. HI farmers adopted biosecurity practices including a willingness to vaccinate for FMD and HS at their own cost, separate sick from healthy cattle, grow and feed forages and displayed awareness of the benefits of building fattening pens. HI farmers that grew forages observed time savings exceeding two hours per day each for men, women and children, enabling expansion of farm enterprises, secondary employment and children's schooling. Logistic regression analysis revealed that farmers in the HI group significantly increased annual household income (P < 0.001), with 53% reporting an increase of 100% or more. We conclude that improving smallholder KAP of cattle health and production can lead to improved livelihoods. This strategy should be of interest to policymakers, donors, researchers and extension workers interested in addressing TAD control, food insecurity and rural poverty in Southeast Asia.

Splenomegaly at a university hospital compared to a nearby county hospital in 317 patients.

Splenomegaly and massive splenomegaly were diagnostically evaluated retrospectively at Stanford University Hospital in 147 patients over 8 years and compared to the nearby county hospital (Santa Clara Valley Medical Center; VMC) in 170 inpatients over 11 years. Hematologic diseases at Stanford (data for VMC in parentheses) occurred in 66% (35%; p < 0.001) of the patients with splenomegaly and in 84% (54%; p < 0.001) of those with massive splenomegaly. Hepatic diseases occurred in 9% (36%; p < 0.001) of the patients with splenomegaly and in 5% (29%; p < 0.001) of those with massive splenomegaly. Splenectomy was performed in 71% of the patients at Stanford and in 9% of those at VMC (p < 0.001). The combined Stanford-VMC series showed significant associations (p < 0.01): for hematologic diseases with massive splenomegaly, lymphadenopathy, and blood cytoses; for hepatic diseases with hepatomegaly, cytopenias as hypersplenism, and abnormal liver function tests, and for infectious diseases with fever.

Splenomegaly in 2,505 patients at a large university medical center from 1913 to 1995. 1963 to 1995: 449 patients.

Splenomegaly was studied retrospectively at the University of California, San Francisco (UCSF), School of Medicine in 301 patients from 1963 to 1995 and compared with the UCSF service of the San Francisco General Hospital Medical Center (SFGH) in 148 patients from 1979 to 1994. The combined 449 patients were classified into several diagnostic groups and were studied by means of several clinical and laboratory associations. Hepatic disease in the percentage of patients at UCSF (with those at SFGH given in parentheses) was associated with splenomegaly in 29% (41%), hematologic disease, 32% (16%); infectious diseases, 16% (36%); congestive or inflammatory disease, 10% (4%); primary splenic disease, 6% (1%); other, 5% (1%); and cause unknown, 2% (1%). Massive splenomegaly occurred in 27% of the patients of the combined series, particularly in patients with hematologic diseases. The acquired immunodeficiency syndrome (AIDS) occurred in more than half of the patients with infectious diseases at SFGH and was four times frequent than in the patients at UCSF. The commonest diseases associated with splenomegaly were hematologic (lymphoma), hepatic (chronic liver disease), infectious diseases (AIDS and endocarditis), congestive (congestive heart failure), primary splenic (splenic vein thrombosis), and other (malignancy not metastatic to the spleen). In 11 patients with AIDS and massive splenomegaly, Mycobacterium avium complex occurred in 8 (73%). Splenectomy was performed in 117 patients (26%), primarily for hematologic amelioration. I conclude that for splenomegaly of unknown origin, the invasive procedure of choice for patients with hematologic associations may be a bone marrow biopsy; for hepatic association, a liver biopsy; and for infectious disease associations, a lymph node biopsy, before any consideration of a diagnostic splenectomy.

Splenomegaly in 2,505 patients in a large university medical center from 1913 to 1995. 1913 to 1962: 2,056 patients.

Splenomegaly was studied retrospectively at the University of California, San Francisco, School of Medicine, on all patients (N = 2,056) for the years 1913 to 1962. The patients were classified into several diagnostic groups, and these groups were tested for statistical significance (chi(2)) with many clinical and laboratory variables to determine their predictive value. Hematologic disorders were associated with 57% of cases of splenomegaly and 81% of cases of massive splenomegaly. Among patients with splenomegaly, 19% had infectious diseases, 11% had hepatic diseases, and 9% had congestive or inflammatory disorders. The residual 4% were considered to have primary splenic disorders or a disorder of unknown cause. The commonest diseases associated with splenomegaly were hematologic (acute and chronic leukemias), infectious (malaria, endocarditis, and tuberculosis), hepatic (chronic liver disease), congestive (congestive heart failure), inflammatory (thyrotoxicosis), and other (cancers not metastatic to the spleen). The diseases most frequently associated with massive splenomegaly were the chronic leukemias. The disease with the highest incidence of massive splenomegaly was myelofibrosis (23 of 29 patients, 78%). Splenectomy was performed in 154 patients (7%), primarily for hematologic amelioration and hepatic hypersplenism. Hematologic diseases showed significant associations with lymphadenopathy, generalized lymphadenopathy, massive splenomegaly, and cytoses (P .001) and with progressive splenic enlargement (P < .02). Infectious diseases showed significant association with fever, and hepatic diseases showed significant association with abnormal results of liver function tests (P < .001). The findings of this retrospective study should be validated prospectively.

Prospective evaluation of anticoagulant reversal with oral vitamin K1 while continuing warfarin therapy unchanged.

STUDY OBJECTIVES: To study the efficacy and safety of partially correcting therapeutic anticoagulation by administering oral vitamin K1. DESIGN: Prospective interventional trial. SETTING: Outpatient anticoagulation clinic. PATIENTS: Patients who required reversal of their normal or excessive therapy with oral anticoagulant drugs were recruited. INTERVENTIONS: All patients received a single oral dose of vitamin K1. The dose was calculated using a regression formula and was intended to decrease the international normalized ratio (INR) to a predetermined value. Patient follow-up continued for 8 weeks. We compared the actual change of the INR to the predicted change. RESULTS: Sixty-five reversals of anticoagulant therapy were initiated in the study group. Sixty-four of the 65 reversals were successful. The mean (+/-SEM) initial INR was 2.6+/-0.1 for the preprocedure patients and 8.4+/-0.5 for the excessively anticoagulated patients. The predicted change in the INR correlated with the actual change (r = 0.92, p < 0.0001). There were no thromboembolic events and only one hemorrhagic complication. The mean (+/-SEM) dose of oral vitamin K1 was 5.0+/-0.3 mg for the preprocedure patients and 10.0+/-1.0 mg for the excessively anticoagulated patients. CONCLUSIONS: The administration of a single oral dose of vitamin K1 is a safe and effective method for partially reversing anticoagulant therapy without disrupting the daily maintenance dose of warfarin. A reliable regression formula was developed to predict the dose of vitamin K1 needed to achieve the desired INR.

Splenomegaly at a United States County Hospital: diagnostic evaluation of 170 patients.

Splenomegaly was studied at a municipal teaching hospital in an 11-year retrospective review. The 170 patients were classified into six diagnostic groups. The associated clinical and laboratory features were tested for statistical association (X2), to determine predictive values. Hepatic diseases caused 36% of the splenomegaly; hematologic, 35%; infectious diseases (ID), 16%; inflammatory, 5%; primary splenic, 4%; and other, 3%. The acquired immunodeficiency syndrome (AIDS) occurred in 54% of patients with ID. Hematologic diseases were significantly associated (P < 0.01) with massive splenomegaly, left upper quadrant (LUQ) abdominal tenderness, and all blood "cytoses." The most common disease with massive splenomegaly was myelofibrosis. Surprisingly, hepatic diseases caused 29% of massive splenomegaly. Hepatic diseases were significantly associated (P < 0.01) with hepatomegaly, abnormal liver-function tests (LFT), and blood "cytopenias." Compared with previous reports, both congestive heart failure and endocarditis now rarely cause splenomegaly. All blood "cytopenias" had highly significant associations (P < 0.01) only with hepatic diseases, which suggests that hypersplenism remains a useful concept for the splenomegaly of liver disease.

Mechanisms of the stereoselective interaction between miconazole and racemic warfarin in human subjects.

Miconazole decreased the total body clearance of both (R)- and (S)-warfarin in normal subjects but did not change volumes of distribution. Miconazole inhibited the oxidation of both (R)- and (S)-warfarin to phenolic metabolites, although (S)-warfarin was inhibited to the greater extent. In particular, (S)-7-hydroxylation, the pathway primarily responsible for termination of the anticoagulant effect, was most strongly inhibited. Inhibition of warfarin hydroxylation by miconazole in human liver microsomes and the in vivo results showed a good rank order correlation. The enhanced anticoagulant effect observed when miconazole and warfarin are coadministered may result from inhibition of P4502C9, the isozyme of P450 primarily responsible for the conversion of (S)-warfarin to (S)-7-hydroxy-warfarin. Because miconazole inhibits a number of P450 isozymes, in addition to P4502C9, it can be expected to lead to interactions with other drugs whose primary metabolism is controlled by these enzymes.

The mechanism of the interaction between amiodarone and warfarin in humans.

Amiodarone decreased the total body clearance of both (R)- and (S)-warfarin in normal subjects but did not change volumes of distribution. Warfarin excretion products were quantified and clearance and formation clearance values calculated. Amiodarone and metabolites inhibited the reduction of (R)-warfarin to (R,S)-warfarin alcohol-1 and the oxidation of both (R)- and (S)-warfarin to phenolic metabolites. Inhibition of warfarin hydroxylation by amiodarone in human liver microsomes was compared with the in vivo results. In agreement, the in vitro data indicates that amiodarone is a general inhibitor of the cytochrome P450 catalyzed oxidation of both enantiomers of warfarin, but the metabolism of (S)-warfarin is more strongly inhibited than that of (R)-warfarin. These data suggest that the enhanced anticoagulant effect observed when amiodarone and warfarin are coadministered is attributable to inhibition of P4502C9, the isozyme of P-450 primarily responsible for the conversion of (S)-warfarin to its major metabolite, (S)-7-hydroxywarfarin.

The mechanism of the warfarin-rifampin drug interaction in humans.

The mechanism of the drug interaction in humans between warfarin and rifampin was investigated by monitoring the elimination kinetics and metabolic disposition of a single oral dose of pseudoracemic warfarin by GC/MS. The decrease in hypoprothrombinemia observed with concomitant administration of therapeutic doses of rifampin was accompanied by a substantial decrease in the elimination half-lives of both warfarin enantiomers. Rifampin increased the clearance of (R)-warfarin threefold and the clearance of (S)-warfarin twofold. The excretion profiles for warfarin and its metabolites in urine and feces were similar for both control and treated subjects with the exception that 4'-hydroxywarfarin (stereoselective for the (S)-enantiomer) was observed when rifampin was administered. 4'-Hydroxywarfarin is a metabolite of the drug hitherto undetected in vivo in humans. Based on formation clearance values estimated for 6-, 7-, and 8-hydroxywarfarin, rifampin appears to increase the clearance of the parent drug by induction of the cytochrome P-450 isozyme(s) responsible for aromatic hydroxylation.

Interaction of amiodarone with racemic warfarin and its separated enantiomorphs in humans.

To evaluate a stereoselective interaction for amiodarone and racemic warfarin, we performed a prospective study with its separated enantiomorphs. Single oral doses of racemic warfarin, 1.5 mg/kg, were administered to six normal subjects, with and without oral amiodarone, 400 mg daily, for the hypoprothrombinemic duration. Both the hypoprothrombinemia (P less than 0.001) and plasma warfarin concentrations (P less than 0.01) were significantly increased. The experiments were repeated separately with the R- and S-warfarin enantiomorphs. S-warfarin with amiodarone significantly increased both the hypoprothrombinemia (P less than 0.001) and plasma warfarin concentrations (P less than 0.01). R-warfarin with amiodarone significantly increased both the hypoprothrombinemia (P less than 0.001) and plasma warfarin concentrations (P less than 0.001). Thus amiodarone augmented the anticoagulant effect nonstereoselectively by reduced metabolic clearance of both warfarin enantiomorphs. Amiodarone and racemic warfarin can be a dangerous combination, particularly when either drug is added to a stabilized regimen of the other drug, unless the prothrombin times are monitored carefully.

The effect of sulfinpyrazone on the disposition of pseudoracemic phenprocoumon in humans.

The effect of sulfinpyrazone on the pharmacokinetics and disposition of the enantiomers of pseudoracemic phenprocoumon was assessed by analyzing serial plasma, urine, and fecal samples for parent drug and metabolites by GC/MS. Essentially all of the administered dose could be accounted for either as parent drug, known metabolites, or their conjugates. Phenprocoumon and the 7-hydroxymetabolite represented the major materials recovered. All drug-related materials excreted into the urine were extensively conjugated. Sulfinpyrazone treatment did not affect the hypoprothrombinemia produced by phenprocoumon nor did it significantly alter the plasma elimination kinetics of the individual (R)- and (S)-enantiomers. However, an apparent increased free fraction of both enantiomers in plasma and inhibition of 7-hydroxylation of (S)-phenprocoumon were observed in the presence of sulfinpyrazone. The results of this study are contrasted with those of a previous study on the interaction between sulfinpyrazone and the structurally similar coumarin anticoagulant warfarin.

The warfarin-sulfinpyrazone interaction: stereochemical considerations.

To allow the simultaneous evaluation of the interaction between sulfinpyrazone and each enantiomer of racemic warfarin, pseudoracemic warfarin (1:1 12C-R(+) and 13C-S(-)warfarin) was given to six normal subjects both before and during oral sulfinpyrazone dosing. Serial blood and urine samples were analyzed for unchanged warfarin and its metabolic products by GC/MS. A mass balance of an oral dose of pseudoracemic warfarin, containing a tracer quantity of 14C-warfarin, was carried out in one of the subjects by monitoring 14C levels in urine and feces for 15 days. Concomitant sulfinpyrazone dosing markedly increased hypoprothrombinemia, decreased clearance of (S)-warfarin, and increased clearance of (R)-warfarin. Sulfinpyrazone also decreased the urinary excretion of warfarin-related products but increased their fecal excretion by an equivalent amount. Virtually all of the administered warfarin dose could be accounted for either as unchanged drug or known metabolites. Pharmacokinetic analysis of the data suggests the following: At least four distinct enzymes (two oxidases and two reductases) are involved in the metabolism of warfarin. Sulfinpyrazone increases the hypoprothrombinemia caused by warfarin primarily by inhibition of the cytochrome P-450-mediated oxidation of (S)-warfarin, the biologically more potent enantiomer. The increased clearance of (R)-warfarin results not from induction, but from its selective displacement from plasma protein binding sites.

Bioavailability of warfarin in a patient with severe short bowel syndrome.

Acquired warfarin resistance has resulted from altered drug metabolism and excessive vitamin K. A third possible mechanism, decreased gastrointestinal absorption of the drug, was examined in a patient with short bowel syndrome and severe malabsorption who demonstrated transient warfarin resistance. Despite the resistance, bioavailability studies demonstrated normal drug absorption and a prolonged half-life. The parenteral administration of vitamin K proved to be the cause of the prolonged warfarin resistance.

Metabolic fate of phenprocoumon in humans.

Samples of urine and feces were collected daily from a normal human volunteer who had received a dose of pseudoracemic phenprocoumon [an equimolar mixture of (R)-[12C]- and (S)-[2-13C]phenprocoumon] containing a tracer dose of 10 microCi of [14C]phenprocoumon and analyzed by TLC, HPLC, and GC-MS. After 25 days, 96% of the radiolabeled material was recovered (62.8% in urine and 33.3% in feces). By isotopic dilution and comparison to the Rf values, retention times, and mass fragmentograms of synthetic standards, the metabolites of the drug were identified as the 4'-, 6-, and 7-hydroxy analogues of phenprocoumon. Virtually all of the recovered radioactivity could be accounted for by the parent drug (approximately 40%) and the three metabolites (approximately 60%). The formation of both 4'-(8.1% of administered dose) and 7- (33.4% of administered dose) hydroxyphenprocoumon was highly stereoselective, giving S/R ratios of 2.86 and 1.69, respectively. The formation of 6- (15.5% of administered dose) hydroxyphenprocoumon showed little stereoselectivity (S/R ratio equal to 0.85). The urinary excretion pattern was also confirmed in four additional healthy male subjects who received a single oral dose of pseudoracemic phenprocoumon and whose urine was analyzed by GC-MS. All the drug-related materials (both hydroxylated metabolites and parent compound) that were excreted into the urine were extensively conjugated.

Hemoglobin E and pregnancy.

Hemoglobin E occurs in 30 million people, primarily Southeast Asians. Their resettlement within the US has dramatically increased the incidence of E hemoglobinopathies. A gravid Vietnamese woman with thalassemia major is reported herein. Her pregnancy was complicated by severe anemia, intrauterine growth retardation, and a paraspinal mass representing extramedullary hematopoiesis. The diagnosis of hemoglobin E/beta o-thalassemia was established when analysis of her hemoglobin showed 60% F, 40% E, and 0% A. The patient was transfused with packed red blood cells to maintain the maternal hematocrit at 30%. A term growth-retarded infant was delivered who had severe thrombocytopenia and an imperforate anus. The infant's thrombocytopenia responded only to infusion of maternal platelets. The differential diagnosis and expected hematologic manifestations of the various E hemoglobinopathies are detailed. Hematologic and obstetric guidelines for management during pregnancy are offered.