Pharmacokinetics of rifampin under fasting conditions, with food, and with antacids

OBJECTIVES: To test a method of measuring the related cost of acute otitis media (AOM) and to provide a preliminary calculation of the indirect and directs costs associated with a single, medically treated episode of AOM. DESIGN: The Otitis Media Diary was used to measure indirect and direct costs associated with AOM in a prospective cohort study. Measured values included the parental time spent in otitis-specific child care and the number and type of medications used. A previously developed economic model was used to calculate the monetary costs associated with the value of caregiver time and the total opportunity cost of AOM. SETTING: The pediatric clinic of Madigan Army Medical Center, Tacoma, Wash. PATIENTS: A cohort of 25 children (12 with AOM and 13 controls) aged 1 to 3 years. MAIN OUTCOME MEASURES: Caregiver time and medication use. RESULTS: The total cost attributable to AOM in the 3-month period following diagnosis was $1330.58 (95% confidence interval, $1008.75-$1652.43), with the majority of that cost stemming from the indirect, rather than direct, costs of illness. After conservative estimates of unmeasured expenses, such as clinic visits and transportation, were accounted for, indirect costs, accrued primarily by parental time, accounted for nearly 90% (95% confidence interval, 87.1%-92.3%) of the total 3-month cost associated with AOM and its medical treatment. The cost items of the Otitis Media Diary were also highly correlated with each other and with other measures of clinical and functional health status. CONCLUSIONS: Otitis Media Diary measures of parental time and medication use appear to provide a more accurate means of calculating the real social costs attributable to the AOM disease process in this cost-effectiveness analysis.     

Temperature requirements of Chrysomya albiceps (Wiedemann, 1819) (Diptera, Calliphoridae) under laboratory conditions

Chrysomya albiceps specimens were obtained from colonies established with larvae and adults collected at the Federal Rural University in Rio de Janeiro, Seropédica, State of Rio de Janeiro. The larval stage of C. albiceps was allowed to develop in climatic chambers at temperatures of 18, 22, 27 and 32 degrees C, and the pupal stage was allowed to develop at 22, 27 and 32 degrees C (60 +/- 10% RH and 14 hr photoperiod). The duration and viability of the larval stage of C. albiceps at 18, 22, 27 and 32 degrees C were 21.30, 10.61, 5.0 and 4.0 days and 76.5, 88.5, 98.5 and 99.5%, respectively, with mean mature larval weights of 45.16, 81.86, 84.35 and 70.53 mg, respectively. Mean duration and viability of the pupal stage at 22, 27 and 32 degrees C were 9.36, 4.7 and 3.0 days and 93.8, 100 and 100%, respectively. The basal temperature for the larval and pupal stage and for the larval and adult phase were 15.04, 17.39 and 15.38 degrees C, corresponding to 65.67, 44.15 and 114.23 DD.     

Microplate-array diagonal-gel electrophoresis (MADGE) and melt-MADGE: tools for molecular-genetic epidemiology

Microplate-array diagonal-gel electrophoresis (MADGE) was invented for molecular-genetic epidemiological studies. It combines direct compatibility with microplates, convenient polyacrylamide-gel electrophoresis and economy of time and reagents at minimal capital cost, and enables one user to run up to several-thousand gel lanes per day for the direct assay of single-base variations. Melt-MADGE adds temporal-thermal-ramp apparatus to achieve similar throughput for de novo mutation scanning.     

Gas chromatographic-mass spectrometric investigations on the formation of phenolic and aromatic hydrocarbons in food (author''s transl)

Experience from arthroscopy in 224 patients with knee complaints is reported. The common method for arthroscopy is compared with a new modification developed during the study. The new method includes introduction of a 5 mm arthroscope through the patellar tendon at the level of the joint line and the use of hooks to test the menisci and the ligaments. The experience from this method shows that it gives an expanded field of vision and that technical failures are less frequent. No complications occurred. It is stated that arthroscopy is of great value in the diagnosis of knee injuries. However, a high diagnostic accuracy can only be reached by an experienced operator using a strictly standardized method.     

Possible role(s) of neurokinins in CNS development and neurodegenerative or other disorders

The present review is an attempt to summarize the diverse literature that suggests a role for neurokinins in a variety of CNS developmental or disease processes. The role of neurokinins in (anti)nociception is well known and is the subject of other comprehensive reviews. The focus of this review is on associations that implicate substance P or other neurokinins in certain aspects of CNS development and in various neuropathologic disorders that have neurodegenerative, psychiatric or other clinical manifestations. Also included are associations related to the central control of some "peripheral" functions. The amount of and degree of evidence for neurokinin involvement in each situation vary from strong to speculative--critical analyses and commentaries on individual methodologies and studies are available from other sources. When viewed in this broad context, the information suggests intrinsic neuroprotective or neurodegenerative properties of neurokinins. It is proposed that these properties delineate a specialized area within the broader field of neurokinin research.     

Immortalized cell lines from embryonic avian and murine otocysts: tools for molecular studies of the developing inner ear

Recently, our studies have focused on genes expressed at the earliest stages of inner ear development. Our aim is to identify and characterize genes that are involved in determining the axes of the semicircular canals, in otic crest delamination and in early innervation of the inner ear. Many elegant studies of auditory development have been done in animal models. However, the need for large amounts of well-characterized embryonic material for molecular studies makes the development of otocyst cell lines with different genetic repertoires attractive. We have therefore derived immortalized otocyst cells from two of the most widely used animal models of ear development: avians and mice. Avian cell isolates were produced from quail otocysts (embryonic stage 19) that were transformed with temperature-sensitive variants of the Rous sarcoma virus (RSV). Among the individual transformed cells are those that produce neuron-like derivatives in response to treatment with 10(-9) M retinoic acid. Mammalian cell isolates were derived from otocysts, of 9 day (post coitus) embryos of the H2kbtsA58 transgenic mouse (Immortomouse), which carries a temperature-sensitive variant of the Simian Virus 40 Tumor antigen. The vast majority of cells of the Immortomouse are capable of being immortalized at 33 degrees C, the permissive temperature for transgene expression, in the presence of gamma-interferon. Several putative clones et these cells differentiated into neuron-like cells after temperature shift and withdrawal of gamma-interferon; another isolate of cells assumed a neuron-like morphology on exposure to brain-derived neurotrophic factor even at the permissive temperature. We describe also a cell isolate that expresses the Pax-2 protein product and two putative cell lines that express the protein product of the chicken equivalent of the Drosophila segmentation gene engrailed. These genes and their protein products are expressed in specific subpopulation of otocyst cells at early stages. Both mouse and quail immortalized cell lines will be used to study inner ear development at the molecular level.     

Utilizing the ultraviolet (UV detect) camera to enhance the appearance of photodamage and other skin conditions

Six isolates of Bacillus pumilus were tested for their ability to inhibit aflatoxin production of Aspergillus parasiticus NRRL 2999 in yeast extract sucrose (YES) broth. Aflatoxin production was inhibited in both simultaneous and deferred antagonism assays, suggesting that the inhibitory activity was due to extracellular metabolites(s) produced in cell-free supernatant fluids of cultured broth. The inhibition was not due to organic acids or hydrogen peroxide produced by B. pumilus since the inhibitory activity was not lost after pH adjustment or treatment of supernatant fluids with catalase. A range of media tested for the production of inhibitory metabolite(s) in supernatant fluids showed that all media supported bacterial growth and production of the metabolite(s). The metabolite(s) were produced over a wide range of temperature (25 to 37 degrees C) and pH (4 to 9) of growth of B. pumilus. They were stable over a wide range of pH (4 to 10) and were not inactivated after autoclaving at 121 degrees C for 30 minutes.     

The precipitation of ammonium uranyl carbonate (AUC): Thermodynamic and kinetic investigations

The aim of this study is to determine the predominant chemical reaction during precipitation of ammonium uranyl carbonate (AUC) based on thermodynamic analysis and to investigate its kinetics. Four chemical reactions were considered. The Gibbs free energies, Δ_rG°(T) derived from the Ulich calculations as a function of temperature have been determined between 293.15 K and 353.15 K. The predominant chemical reaction of AUC precipitation was UO₂(NO₃)₂·6H₂O_(aq) + 6NH_3(g) + 3CO_2(g) → (NH₄)₄UO₂(CO₃)_3(s) + 2NH₄NO_3(aq) + 3H₂O_(l). According to the AUC precipitation kinetics results, the reaction best fits a second order rate equation. The rate constants k₂ were calculated at 313.15 K and 330.15 K and the activation energy E_a determined using the Arrehenius equation was found as 17.4 kJ/mol.     

A human combined hepatocellular and cholangiocarcinoma cell line (KMCH-2) that shows the features of hepatocellular carcinoma or cholangiocarcinoma under different growth conditions

BACKGROUND/AIMS: Combined hepatocellular and cholangiocarcinoma is a rare tumor of the liver, and its histogenesis remains unclear. The authors addressed this issue in the current article. METHODS: A specimen aseptically obtained from the surgically resected combined hepatocellular and cholangiocarcinoma was processed for primary culture. The morphologic features of the established cell line cultured on a plastic dish and in type I collagen gel matrix, and transplanted in nude mice were examined. RESULTS: The authors established a new human combined hepatocellular and cholangiocarcinoma cell line, designated KMCH-2, from a 40-year-old Japanese man. KMCH-2 cells on a plastic dish proliferated in a monolayered sheet with a population doubling time of 32 to 44 h. KMCH-2 expressed functional characteristics of hepatocellular carcinoma, such as albumin synthesis at protein and mRNA levels, but were poorly differentiated in morphology, showing an overlap of features with cholangiocarcinoma. KMCH-2 cells cultured within type I collagen gel matrix proliferated, forming compact to vaguely trabecular and pseudoglandular arrangements, and differentiated to show morphological characteristics of hepatocellular carcinoma unlike the cells on a plastic dish. Mucin production was not detected in KMCH-2 cells in vitro. Subcutaneous tumors which developed in nude mice injected with KMCH-2 cells represented features of adenocarcinoma with mucin production. CONCLUSIONS: The present results revealed the presence of an albumin-producing human hepatic neoplastic cell, such as KMCH-2, that can differentiate to show not only the features of hepatocellular carcinoma but also those of cholangiocarcinoma under certain growth conditions.     

Blood preservation and air transport: study of physical constraints (temperature and pressure)

We study physical compulsions of packed red cells during air transport. We found important variations of pressure and temperatures in blood transport box. These variations explain the biological alterations found in the first part. New rules for blood air transport are proposed.     

Prevalence of hyperapobetalipoproteinemia and other lipoprotein phenotypes in men (aged < or = 50 years) and women (< or = 60 years) with coronary artery disease

The prevalence and clinical characteristics of hyperapobetalipoproteinemia (hyperapoB) and other phenotypes of dyslipoproteinemia were examined in 99 men (aged < or = 50 years) and 104 women (< or = 60 years) undergoing elective diagnostic coronary arteriography. HyperapoB was the most common phenotype (34%) associated with premature coronary artery disease (CAD). Only 20.2% of patients with CAD had a normal lipoprotein phenotype. The significant odds ratios for CAD were as follows: hypertriglyceridemic hyperapoB 17.45 (p < 0.0001), type IV 6.54 (p = 0.0001), type IIa 4.73 (p = 0.008), normotriglyceridemic hyperapoB 2.54 (p = 0.03) and type IIb 8.73 (p = 0.05). The strong association of hypertriglyceridemic hyperapoB with CAD reflected the multiplicative effect of increased low-density lipoprotein apolipoprotein B and endogenous hypertriglyceridemia, and was independent of the effects of age, sex, diabetes mellitus, systemic hypertension, body mass index and cigarette smoking. The ratio of apolipoprotein B to A-1 was better than those of low-density to high-density lipoprotein cholesterol and total to high-density lipoprotein cholesterol at discriminating dyslipidemic phenotypes from normal. Obesity was increased approximately 1.5 to two-fold in the hypertriglyceridemic phenotypes, diabetes was more prevalent in hypertriglyceridemic hyperapoB (6.8-fold; p < 0.001) and type IV (4.4-fold; p = 0.02), and hypertension was increased 1.5- to twofold in most dyslipidemic groups. The data indicate that hyperapoB and endogenous hypertriglyceridemia both contribute to the risk of premature CAD.     

Daily energy expenditure in free-living conditions in obese and non-obese children: comparison of doubly labelled water (2H2(18)O) method and heart-rate monitoring

OBJECTIVE: To compare the heart-rate monitoring with the doubly labelled water (2H2(18)O) method to estimate total daily energy expenditure in obese and non-obese children. DESIGN: Cross sectional study of obese and normal weight children. SUBJECTS: 13 prepubertal children: six obese (4M, 2F, 9.1 +/- 1.5 years, 47.3 +/- 9.7 kg) and seven non-obese (3M, 4F, 9.3 +/- 0.6 years, 31.8 +/- 3.2 kg). MEASUREMENTS: Total daily energy expenditure was assessed by means of the doubly labelled water method (TEEDLW) and of heart-rate monitoring (TEEHR). RESULTS: TEEHR was significantly (P < 0.05) higher than TEEDLW in obese children (9.47 +/- 0.84 MJ/d vs 8.99 +/- 0.63 MJ/d) whereas it was not different in non-obese children (8.43 +/- 2.02 MJ/d vs 8.42 +/- 2.30 MJ/d, P = NS). The difference of TEE assessed by HR monitoring in the obese group averaged 6.2 +/- 4.7%. At the individual level, the degree of agreement (difference between TEEHR and TEEDLW +/- 2s.d.) was low both in obese (-0.36, 1.32 MJ/d) and in non-obese children (-1.30, 1.34 MJ/d). At the group level, the agreement between the two methods was good in nonobese children (95% c.i. for the bias:-0.59, 0.63 MJ/d) but not in obese children (0.04, 0.92 MJ/d). Duration of sleep and energy expenditure during resting and physical activity were not significantly different in the two groups. Patterns of heart-rate (or derived energy expenditure) during the day-time were similar in obese and non-obese children. CONCLUSION: The HR monitoring technique provides an estimation of TEE close to that assessed by the DLW method in non-obese prepubertal children. In comparison with DLW, the HR monitoring method yields a greater TEE value in obese children.     

Biodegradabilities of ethylenediamine-N,N'-disuccinic acid (EDDS) and other chelating agents

Biodegradabilities of chelating agents were tested with activated sludge. Ethylenediaminetetraacetic acid (EDTA) remained intact in the effluent even after acclimation for 100 days, but propanediamine-N,N'-disuccinic acid (PDDS) and nitrilotriacetic acid (NTA) were biodegraded after acclimation for 5 and 23 days, respectively. Optical isomers of ethylenediamine-N,N'-disuccinic acid (EDDS) had different biodegradabilities: SS- and RS-isomers were susceptible to biodegradation, but the RR-isomer was resistant. SS-isomer was degraded even by activated sludge without acclimation.     

13C NMR, X-ray, and differential scanning calorimetry investigations of truncated BPTI (aprotinin) analogues

Truncated BPTI missing residues 1 and 2 is investigated together with variants thereof (Lys-15, Arg-17, and Arg-42 are replaced by other residues in various combinations). A comparison of the X-ray structure of BPTI with that of 3-58BPTI(K15R,R17A,R42S) shows only minor variations for the backbone, but the lack of salt bridge between the terminals and the lack of two N-terminal residues provide a structure open at one end. Comparisons of amide exchange rates show a dramatic increase for the most slowly exchanging NH protons of 3-58BPTI and the analogues thereof, as compared to those of the wild-type despite only small differences in the structures. The amide exchange rates for truncated analogues increase with decreasing TTEP (temperature top endothermic peak) values. On the basis of the known structural changes comparisons to 13C chemical shifts are made. 13C chemical shifts are assigned using the D-isotope and HMBC techniques. Excellent resolution is obtained in these 1D natural abundance spectra. 13C NMR chemical shifts are shown to be able to gauge structural changes. A comparison of 13C chemical shifts of WT BPTI (aprotinin) and 3-58BPTI reveals effects caused by (i) the removal of the salt bridge of the terminii, (ii) the charge of the N-terminus, and (iii) the increased mobility of the side chain of Tyr-23. Small effects are also seen due to a conformational change of the aromatic ring of Phe-4. Ring current shifts at 13C chemical shifts are calculated. The difference in the calculated ring current effects are small comparing the wild-type with 3-58BPTI(K15R,R17A,R42S) provided the structures are relaxed. Protein unfolding as a function of pH and temperature is studied by DSC. Unfolding occurs at lower temperature with N-terminally truncated analogues, and the maximum is shifted toward higher pH.