Ion Velocity Measurements for the Ionospheric Connections Explorer.

The Ionospheric Connections Explorer (ICON) payload includes an Ion Velocity Meter (IVM) to provide measurements of the ion drift motions, density, temperature and major ion composition at the satellite altitude near 575 km. The primary measurement goal for the IVM is to provide the meridional ion drift perpendicular to the magnetic meridian with an accuracy of 7.5 ms-1 for all daytime conditions encountered by the spacecraft within 15° of the magnetic equator. The IVM will derive this parameter utilizing two sensors, a retarding potential analyzer (RPA) and an ion drift meter (IDM) that have a robust and successful flight heritage. The IVM described here incorporates improvements in the design and operation to produce the most sensitive device that has been fielded to date. It will specify the ion drift vector, from which the component perpendicular to the magnetic field will be derived. In addition it will specify the total ion density, the ion temperature and the fractional ion composition. These data will be used in conjunction with measurements from the other ICON instruments to uncover the important connections between the dynamics of the neutral atmosphere and the ionosphere through the generation of dynamo currents perpendicular to the magnetic field and collisional forces parallel to the magnetic field. Here the configuration and operation of the IVM instrument are described as well as the procedures by which the ion drift velocity is determined. A description of the subsystem characteristics, which allow a determination of the expected uncertainties in the derived parameters, is also given.

Pecans lower low-density lipoprotein cholesterol in people with normal lipid levels.

OBJECTIVE: To compare serum lipid profiles and dietary intakes of people with normal lipid levels who consumed pecans and those who did not consume nuts. DESIGN: Eight-week, randomized, controlled study of pecan treatment group vs control group. SUBJECT: Nineteen people with normal lipid levels completed the study; 10 had been randomly assigned to the pecan treatment group (7 women, 3 men, mean age = 45 +/- 10 years) and 9 to the control group (8 women, 1 man, mean age = 37 +/- 12 years). INTERVENTION: The pecan treatment group consumed 68 g pecans per day for 8 weeks plus self-selected diets. The pecans contributed 459 kcal and 44 g fat daily. The control group avoided nuts and consumed self-selected diets. MAIN OUTCOME MEASURES: Total serum cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and total triglyceride levels were measured at the time of entrance to the study (baseline), week 4, and week 8. Computer analyses were done on five 3-day food records. STATISTICAL ANALYSIS: Comparisons were made using analysis of variance or paired t test. RESULTS: LDL-C was lowered in the pecan treatment group from 2.61 +/- 0.49 mmol/L at baseline to 2.35 +/- 0.49 at week 4 (P < .05) and to 2.46 +/- 0.59 at week 8 (P < .05). At week 8, total cholesterol and HDL-C in the pecan treatment group were significantly lower (P < .05) than in the control group (total cholesterol: 4.22 +/- 0.83 vs 5.02 +/- 0.54 mmol/L; HDL-C: 1.37 +/- 0.23 vs 1.47 +/- 0.34 mmol/L). Dietary fat, monounsaturated fat, polyunsaturated fat, insoluble fiber, magnesium, and energy were significantly higher in the pecan treatment group than in the control group. Body mass indexes and body weights were unchanged in both groups. APPLICATIONS: Pecans can be included in a healthful diet when energy intake and potential weight gain are addressed.

The role of ursodeoxycholic acid in bile acid-mediated kidney fragment toxicity.

Elevated levels of bile acids are thought to play an important role in the renal failure of patients with obstructive jaundice undergoing surgery. In contrast, ursodeoxycholic acid (UDA) is widely used to improve cholestasis and has been proposed as protective bile acids and antioxidant. The present study employs kidney fragments to determine the role of reactive oxygen species (ROS) in the mechanism of toxicity of hydrophobic bile acids and to determine the nephroprotectant properties of UDA against the hydrophobic bile acids. The hydrophobic bile acids chenodeoxycholic (200 microM) and deoxycholic acid (200 microM) significantly (P<0.05) increased lactate dehydrogenase leakage (LDH) from glomerular fragments from 2.7+/-0.4 to 5.03+/-0.23 and 4.66+/-0.37 (micromol NADH consumed/min/mg protein) for chenodeoxycholic and deoxycholic acid respectively. Preincubating the fragments with UDA (500 microM) did not prevent the leakage of LDH caused by the bile acids. The level of lipid peroxidation was not increased in fragments exposed to either ursodeoxycholic (0-500 microM), lithocholic (0-100 microM), chenodeoxycholic (0-500 microM) or deoxycholic acid (0-500 microM). Furthermore UDA (500 microM) did not prevent the increase in lipid peroxidation caused by tert-butyl hydroperoxide (0-1000 microM) in the fragments. These results suggest that hydrophobic bile acids do not cause lipid peroxidation in kidney fragments and that UDA is neither capable of preventing the loss of membrane integrity induced by hydrophobic bile acids or acting as an antioxidant in kidney fragments.

Methapyrilene hepatotoxicity is associated with oxidative stress, mitochondrial disfunction and is prevented by the Ca2+ channel blocker verapamil.

Methapyrilene (MP) is an unusual hepatotoxin in that it causes periportal necrosis in rats. The mechanism of acute methapyrilene hepatotoxicity has, therefore, been investigated in cultured male rat hepatocytes. Addition of methapyrilene to rat hepatocytes resulted in a time- and dose-dependent loss in cell viability between 4 and 8 h of incubation as judged by cellular enzyme leakage. The cytochrome P450 (CYP) inhibitor metyrapone protected against methapyrilene-mediated toxicity suggesting that MP is metabolised by CYP for toxicity. The concentration-dependent protection from methapyrilene toxicity afforded by metyrapone correlated with an inhibition of microsomal CYP2C11-associated androstenedione 16alpha hydroxylase activity, and hepatocytes prepared from hypophysectomised rats (containing reduced levels of microsomal immunodetectable CYP2C11 and associated androstenedione 16alpha hydroxylase activity) showed resistance to the toxic effects of methapyrilene. These data suggest that the toxicity of methapyrilene is predominantly dependent on the CYP2C11 isoform. Treatment of hepatocytes with a toxic concentration of MP caused oxidative stress as indicated by increases in NADP+ levels within 2 h and cellular thiol oxidation as evidenced by a reduction--but not complete loss--in glutathione levels. Methapyrilene hepatotoxicity was associated with an early loss in mitochondrial function, as indicated by mitochondrial swelling and significant losses in cellular ATP within 2 h. Co-incubation of methapyrilene-treated hepatocytes with inhibitors of inner mitochondrial transition permeability pore opening--cyclosporin A or the thiol reductant dithiothreitol--abrogated cell death suggesting that pore opening and loss of mitochondrial Ca2+ homeostasis play a significant role in methapyrilene-mediated cell death. Co-incubation of methapyrilene-treated hepatocytes with the phenylalkylamine calcium channel blocker verapamil--but not by treating cells in a nominally calcium-free medium--also abrogated cell death, suggesting that if Ca2+ is involved in cell killing then it is dependent on an intracellular Ca2+ pool. Pre-treatment of hepatocytes for 1 h with verapamil--to inhibit intracellular Ca2+ pool filling--increased the potency of verapamil protection against methapyrilene toxicity by approximately 100-fold. Taken together, these data indicate that methapyrilene intoxication leads to mitochondrial disfunction and suggest a critical role for a loss of mitochondrial Ca2+ homeostasis in this model of hepatocyte death.

Cat-scratch disease simulating Histiocytosis X.

Cat-scratch disease is a self-limited condition commonly causing a benign chronic lymphadenopathy in children. Osteolytic lesions are a rare complication, but have been previously reported. We report a case of a solitary osteolytic lesion of the skull whose clinical, radiographic and pathological features were initially interpreted as being consistent with Histiocytosis X. Subsequently, positive serological titers for Bartonella, a history of a cat-scratch antecedent to the onset of clinical symptoms and review of the original histopathology confirmed the diagnosis of cat-scratch disease. We reviewed the English language literature on osteolytic lesions associated with cat-scratch disease and compare the current case with those previously reported.

The relationship between sodium chloride concentration and bile acid cytotoxicity in cultured kidney cells.

Patients with obstructive jaundice suffer an increased incidence of mortality from post operative renal failure, which may be related to elevated circulating bile salts. This study assesses the effects of increased ionic strength (similar to that found in the kidney inner medulla) on bile salt critical micellar concentration (CMC) and cytotoxicity to renal medullary epithelial primary cultures and MDCK and NRK cell lines representing the distal and proximal tubular cells respectively. The CMC of chenodeoxycholic acid decreased from 2.86 +/- 0.07 (in isotonic Earle's Hepes buffer) to 2.30 +/- 0.07, 1.99 +/- 0.09 and 1.46 +/- 0.08 mM following the addition of 150, 250 and 500 mM NaCl. Similarly, the CMC of deoxycholic acid was reduced from 3.18 +/- 0.1 to 2.84 +/- 0.1, 2.26 +/- 0.1 and 1.79 +/- 0.09 mM by the addition of 150, 250 and 500 mM NaCl. Increasing the ionic strength of the culture medium of medullary epithelial cells by the addition of 150 mM NaCl, decreased viability by 39% (p < 0.01), 24% (p < 0.001) and 40% (p < 0.001) for lithocholic (25 microM), chenodeoxycholic (100 microM) and deoxycholic acids (100 microM), respectively. A similar increase in the ionic strength of the culture medium of MDCK cells decreased viability by 79% (p < 0.01), 46% (p < 0.01) and 15% (p < 0.01) for lithocholic (15 microM), chenodeoxycholic (100 microM) and deoxycholic (50 microM), respectively. Adding 200 mM urea to medium supplemented with 150 mM NaCl (to further increase osmolality but not ionic strength) had no effect on the cytotoxicity bile salts in MDCK cells. The addition of 150 mM NaCl to the culture medium of NRK cells resulted in a decrease viability of 15% (p < 0.01), 27% (p < 0.01) and 60% (p < 0.01) following exposure to either lithocholic (15 microM), chenodeoxycholic (50 microM) or deoxycholic acids (50 microM) respectively. These results show that increasing NaCl concentrations lowers CMC of bile salts and increase cytotoxicity in medullary epithelial primary, MDCK and NRK cells. This suggests that the high NaCl levels in the kidney inner medulla would reduce bile salt CMC such that they could damaged renal cells. This may, in part, explain the increased susceptibility of the kidney during obstructive liver disease.

The role of reactive oxygen species in adriamycin and menadione-induced glomerular toxicity.

Redox cycling leading to oxidative stress has been proposed as the mechanism by which adriamycin induces glomerular toxicity in rats. The present study compares the extent of the oxidative stress and cytotoxicity induced by adriamycin to menadione (a model redox cycling quinone) in freshly isolated rat glomeruli. Adriamycin and menadione (25 microM) decreased de novo protein synthesis (measured by 3H-proline incorporation into acid-precipitable glomerular protein) by 50 and 85%, respectively, in 2 h. By contrast, menadione at 25 microM reduce glomerular membrane integrity (as assessed by lactate dehydrogenase leakage), adriamycin reduced membrane integrity at 500 microM adriamycin. Reactive oxygen species (ROS) were measured by the oxidation of dihydrodichlorofluorescein. Menadione (25 microM) and adriamycin (25 microM) increased ROS formation to 260 and 156% of controls after 30 min incubation, respectively. Oxidative stress was assessed by measuring the intracellular level of reduced glutathione (GSH) and the decrease of the NADPH/NADP- ratio which stimulates the pentose phosphate pathway (PPP): (a) menadione (25-100 microM) reduced glomerular GSH to 10-20% of controls, adriamycin (25-100 microM) had no effect; (b) menadione (10 microM) increased PPP activity 6-fold, while adriamycin (125 microM) had only a 2-fold effect. Although adriamycin and menadione generate extensive ROS and decrease protein synthesis, there was no correlation between the extent of oxidative stress and cytotoxicity in glomeruli exposed to adriamycin. These results suggest that oxidative stress may not be the primary mechanisms by which adriamycin induces selective glomerular toxicity.

Relationship between acute toxicity of (bis)aziridinylbenzoquinones and cellular pyridine nucleotides.

The toxicity of aziridinylbenzoquinones may occur by a number of mechanisms, including oxidative stress caused by redox cycling and the activation of the aziridine groups. Isolated hepatocytes were used to assess the relationship between the redox status of NADP(H) associated with oxidative stress, the level of NAD(H) closely linked with DNA repair and the cytotoxicity of three 2,5-bis(aziridinyl)-1,4-benzoquinones (BABQ). Exposure of hepatocytes to the BABQ TW13 (200 microM) and TW25 (100 microM), which are able to arylate and to redox cycle, resulted in increased intracellular NADP+ from < 0.3 nmol/mg protein to 1.5 nmol/mg protein within 60 min. The increase in intracellular NADP+ was followed by the onset of cell death by 180 min. In contrast, exposure to lower concentrations of TW13 (100 microM), TW25 (50 microM) and carboquone (100-200 microM) (which neither arylates nor redox cycles via a one-electron reduction) resulted in a less pronounced (< 1.0 nmol/mg) increase in NADP+ and there was no evidence of cell death within the 180 min incubation. BABQ had a concentration dependent effect on intracellular NAD+. Exposure of hepatocytes to TW13 (200 microM) and TW25 (100 microM) resulted in a decrease in intracellular NAD+ from > 2.7 to < 1.0 nmol/mg protein within 60 min. At concentrations of the BABQ where the level of NAD+ remained > 1.0 nmol/mg protein after 30 min, the hepatocytes remained viable at 180 min. These changes in intracellular pyridine nucleotides suggests two mechanisms may be involved in BABQ cytotoxicity. At high concentrations, aziridinylbenzoquines may cause cytotoxicity via oxidative stress following redox cycling. At lower concentrations however, the predominant pyridine nucleotide change is a prolonged depletion of NAD+, suggesting extensive DNA damage which may lead to delayed cell death.

The Army dietitian in Panama: military hospital feeding and humanitarian efforts during Operation Just Cause.

The delivery of nutrition during a military conflict creates added demands on food service operations. Dietitians in the United States Army assisted the civilian population in Panama by participating in humanitarian feeding efforts during Operation Just Cause from December 1989 to January 1990. They provided hospital nutrition under combat conditions and assisted in a displaced-persons camp by developing an Emergency Food Plan that incorporated indigenous foods. The Army Medical Specialist Corps instituted training programs to prepare Army dietitians for refugee feeding in the post-Cold War era as a result of the lessons learned during this and other humanitarian efforts.

DNA single-strand breakage in mammalian cells induced by redox cycling quinones in the absence of oxidative stress.

Quinone-induced cell death is often attributed to oxidative stress during which the formation of DNA strand breaks is thought to play an important role. In this study, extensive DNA damage was observed in human chronic myelogenous leukemic cells (K562) exposed for 15 minutes to low concentrations (15-100 microM) of the redox cycling quinones 2,3-dimethoxy-1,4-naphthoquinone (2,3-diOMe-1,4-NQ) and menadione. However, DNA strand breakage and cell death could not be attributed to oxidative stress as the intracellular level and redox status of the reducing equivalents NADP(H) and GSH were unaffected. The intracellular level of NAD+ was found to correlate well with the extent of DNA repair (r = 0.93, P < 0.02) and cell proliferation (r = 0.96, P < 0.01) in cells exposed to the quinones. In contrast, a significant decrease in the level of intracellular ATP was only observed in cells exposed to menadione (50-100 microM). These results suggest that redox cycling quinones are capable of inducing DNA damage in mammalian cells by a mechanism that does not involve oxidative stress. Following DNA damage, cell death is dependent on the availability of NAD+, which may be key to the rapid repair of strand breaks.

Pyridine nucleotide hydrolysis and interconversion in rat hepatocytes during oxidative stress.

A characteristic feature of many types of chemically induced oxidative stress is a depletion of the pyridine nucleotide NAD+. This has been attributed to either its hydrolysis to nicotinamide and ADP-ribose or to its phosphorylation (interconversion) to NADP+. In this study the exposure of rat hepatocytes to either tert-butyl hydroperoxide (250-750 microM) or 2,3-dimethoxy-1,4-naphthoquinone (50 microM) resulted in a rapid depletion of NAD+ with no change in the level of NAD. The depletion of NAD+ was accompanied by an increase in nicotinamide. The rate of NAD+ deletion induced by tert-butyl hydroperoxide (500 microM) and 2,3-dimethoxy-1,4-naphthoquinone (50 microM) was reduced by preincubating the hepatocytes for 1 hr with either 3-aminobenzamide (20 mM), nicotinamide (10 mM) or theophylline (7.5 mM), potent inhibitors of poly(ADP-ribose)polymerase. In cells exposed to 2,3-dimethoxy-1,4-naphthoquinone (50 microM) extensive oxidation of NADPH to NADP+ was observed; this was followed by an increase in the level of NADP(+) + NADPH (NADP(H)). However, no change in the total pyridine nucleotide (NAD(H) + NADP(H)) pool was detected. Exposure to tert-butyl hydroperoxide resulted in the oxidation of NADPH to NADP+ and a decrease in total pyridine nucleotide pool. These results suggest that during oxidative stress, NAD+ is hydrolysed to nicotinamide, possibly by the activation of poly(ADP-ribose)polymerase and that the depletion of NAD+ is independent of the increase in NADP+. Furthermore, no evidence of an interconversion of NAD+ to NADP+ was found.

A comparison of fish oil or corn oil supplements in hyperlipidemic subjects with NIDDM.

OBJECTIVE: To examine the effects on blood lipids and glycemic control of fish oil and corn oil supplementation at two levels in subjects with hyperlipidemia and non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Forty subjects (18 men and 22 women; aged 53.9 +/- 7.0 years) with NIDDM and hyperlipidemia were randomly assigned to one of four treatment groups: 9 g of fish oil, 18 g of fish oil, 9 g of corn oil, or 18 g of corn oil daily supplementation for 12 weeks. RESULTS: The level of oil supplements (9 g compared with 18 g) did not have a significant effect within each oil group on glycemic control and lipids. Significant differences (P < 0.05) in lipids were found when the 9-g and 18-g groups were combined. In subjects consuming fish oil, plasma very-low-density lipoprotein (VLDL) cholesterol (P = 0.0001), plasma triglyceride (TG) (P = 0.0001), and plasma VLDL TGs (P = 0.02 at 6 weeks and P = 0.0001 at 12 weeks) were significantly lowered compared with subjects consuming corn oil. Plasma VLDL cholesterol increased across time in the corn oil group (P = 0.04). Plasma low-density lipoprotein (LDL) cholesterol was temporarily increased (P = 0.008) in the fish oil group at 6 weeks, but the effect was no longer present at 12 weeks. No significant differences between fish oil- or corn oil-supplemented diets were found in total plasma cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose, glycosylated HbA1c, weight, and blood pressure. CONCLUSIONS: In this study, fish oil supplementation improved plasma VLDL cholesterol, VLDL TGs, and total TGs while having a transient deterioration in LDL cholesterol in subjects with NIDDM. Furthermore, fish oil supplementation had no significant deleterious effect on glycemic control.

The clinical education of primary care nurse practitioner students.

Directors of 112 ambulatory care nurse practitioner (NP) programs were surveyed to determine the amount and characteristics of the clinical education of their students. The response rate was 53%. Among all programs, students experienced an average of 597 clinical hours. This number was somewhat higher among family and women's health nurse practitioner programs. The range was large--192 to 1600 hours--however, eliminating both extremes left a majority of programs within a much narrower range; the central 62% of programs were between 400 and 700 hours. Certificate programs reported more hours than did masters programs. Almost all hours were in ambulatory settings, which included a wide mixture of public and private settings. A majority of students experience part of their clinical training along with medical residents and medical students, and often with NP students from other programs and with physician assistant students. Most NP program directors find these other disciplines' programs cooperative, and the NP directors favor stronger relationships.

Using State Board of Nursing data to estimate the number of nurse practitioners in the United States.

Knowing the number of nurse practitioners, both at the state and national levels, is important to those dealing with health care policy and education. To determine these numbers, we telephoned all state boards of nursing, and asked whether they distinguished nurse practitioners from other registered nurses and what the respective numbers were. Data were available from a time period beginning in March 1992 and ending in September 1992. Thirty-four states, representing 70.6 percent of all registered nurses, now distinguish nurse practitioners from other nurses. In these states, 1.35 percent of all registered nurses are nurse practitioners. Projecting this percentage to the states that do not make the distinction yields a total of 33,834 nurse practitioners in the United States. Using neighboring states rather than the national average as a predictor for no-data states leads to a national total estimate of 31,294. When corrected for multistate licensure, the final estimated number is 27,226. This estimating method should yield even more accurate data in the future as more states certify and list their nurse practitioners. This method enumerates nurse practitioners as defined by the various states, which have highly variable definitions of what a nurse practitioner is. However, the variability in legal definition is decreasing as more states require national certification.

Will family physicians really return to obstetrics if malpractice insurance premiums decline?

BACKGROUND: The loss of family physicians as obstetrics providers during the last decade has had a significant impact on access to obstetric services, especially for rural populations. The expense of malpractice premiums has been cited often as a reason for physicians' discontinuation of this service. METHODS: Seventy-six family physicians in northern California who recently discontinued obstetrics were surveyed regarding their decisions related to obstetric practice. Those physicians who indicated that a decrease in malpractice premiums would allow them to consider resuming obstetrics were resurveyed by telephone the following year. This telephone survey occurred following a 25 percent decrease in malpractice premiums for obstetrics by the major malpractice insurance carrier for family physicians practicing obstetrics in the study area. RESULTS: Twenty-nine of the 76 physicians in the original survey who had recently discontinued obstetrics stated they would consider resuming if conditions changed. Twenty-six (90 percent) of these physicians indicated that malpractice premiums needed to change for them to consider resuming obstetrics. Following the reduction in premiums, none of these physicians reported plans to resume obstetrics or even a likelihood that they would be resuming obstetrics. CONCLUSION: This study found that family physicians who discontinued obstetrics and cited malpractice premiums as a barrier to resuming obstetrics are unlikely to resume when rates decline. This finding suggests that other issues might be equally or more important in this decision.

Quinone-induced DNA single strand breaks in rat hepatocytes and human chronic myelogenous leukaemic K562 cells.

In rat hepatocytes exposed to the quinones menadione and 2,3-dimethoxy-1,4-naphthoquinone (2,3-diOMe-1,4-NQ) a decrease in NAD+ is observed. DNA damage and activation of poly(ADP-ribose)polymerase are often associated with a decrease in NAD+. Using rat hepatocytes and human myeloid leukaemic cells (K562), we examined the extent of DNA damage induced by these quinones at non-toxic concentrations, i.e. at concentrations at which the cells completely exclude the dye trypan blue. Both quinones caused significant DNA damage at very low concentrations (5-100 microM). With 2,3-diOME-1,4-NQ (15 microM) or menadione (15 microM) single strand breaks (SSB) were observed at very early time points (less than 5 min), reaching a maximum between 20 and 30 min. Most SSB were repaired within 45 min of the removal of the quinones. Whilst extensive repair was observed within 4 hr of the removal of 2,3-diOMe-1,4-NQ (15 microM), only partial repair was observed following exposure to menadione (15 microM). SSB induced by 2,3-diOMe-1,4-NQ (15 microM) were completely inhibited by the iron chelator 1,10-phenanthroline (25 microM), whereas in cells exposed to menadione (15 microM) they were only partially inhibited. Finally, although the membrane integrity of K562 cells was unaffected by exposure to high concentrations of both quinones (less than or equal to 400 microM), cytostasis was observed at much lower concentrations (50 microM). Our results demonstrate that at very low concentrations these quinones induce extensive DNA damage possibly caused by hydroxyl radicals. The DNA damage was accompanied by an early cytostasis but no loss of membrane integrity.

A new mechanism for the formation of meteoritic kerogen-like material.

The carbon in ancient carbonaceous chondritic meteorites is mainly in a hydrocarbon composite similar to terrestrial kerogen, a cross-linked structure of aliphatic and aromatic hydrocarbons. Until recently, the composite has been commonly thought to have been produced in the early solar nebula by a Fischer-Tropsch-type process, involving the catalytic synthesis of hydrocarbons from carbon monoxide and hydrogen on grain surfaces. Instead, the aromatic hydrocarbons may form in gas-phase pyrolysis of simple aliphatics like acetylene and methane by a mechanism developed recently to explain formation of soot in combustion and of aromatic molecules in circumstellar envelopes. Nonequilibrium chemical kinetic calculations indicate that this mechanism can produce meteoritic aromatics if the initial concentration of simple hydrocarbons in the solar nebula was sufficiently but not unreasonably high.