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Spondyloepiphyseal dysplasia tarda (SEDT) is a genetically heterogeneous disorder often associated with the early onset of osteoarthrosis. The X-linked recessive form (SEDL) affects men and is characterized by reduced height, arm span exceeding total height, and barrel chest deformity. The radiographic phenotype comprises a hump-shaped deformity of vertebral bodies and mild epiphyseal dysplasia of the femoral head associated with early signs of hip arthrosis. The disorder is caused by mutations in the SEDL (or sedlin) gene on Xp22.12-p22.31. In 4 male patients from a German family, we identified a new nonsense mutation in SEDL exon 4 (C74A). The carrier status for the mutation could be confirmed in 2 women of the family, both of whom show no obvious signs of bone and joint diseases. SEDT should be kept in mind as a differential diagnosis in men with early "primary" bilateral osteoarthrosis.

Study Design: Report of a family affected with X-linked spondyloepiphyseal dysplasia tarda with special respect to radiologic alterations of the spine from puberty to the forth decade and to molecular analysis of the underlying genetic defect., Objectives: To report the typical radiologic presentation of patients with X-linked spondyloepiphyseal dysplasia tarda and the diagnostic tool of mutation screening for that disease in order to avoid confusion with similar occurrences., Summary of Background Data: Spondyloepiphyseal dysplasia tarda is a genetically heterogeneous disorder that frequently manifests itself with back pain starting around puberty. The X-linked recessive form (X-linked spondyloepiphyseal dysplasia tarda) affects males and is clinically characterized by an arm span markedly exceeding total height, a barrel chest deformity, and early development of degenerative joint disease. The disorder is caused by mutations in the SEDL gene located on Xp22.12-p22.31., Methods: Radiologic alterations of the cervical, thoracal, and lumbar spine were assessed in the affected family members and one suspected female carrier in correlation to age. All 6 exon codings for the SEDL gene were analyzed by primer cycle sequencing., Results: In 3 male patients from a French family, we identified a 5 base pair deletion in SEDL, exon 5 at position 267-271 (delAAGAC). Carrier status for the mutation could be confirmed in one female member of the family, which is inconspicuous in terms of spine and joint diseases. Radiologic abnormalities of the patients comprised generalized platyspondyly, a hump-shaped deformity of cervical, thoracal, and lumbar vertebral bodies as well as signs of retrospondylophytes, osteochondrosis, and spondylarthrosis., Conclusions: X-linked spondyloepiphyseal dysplasia tarda should be kept in mind as a differential diagnosis in men with early onset of back pain and radiologic abnormalities of the vertebral bodies comprising platyspondyly and a central hump.

The reactions of [fac-Re(CO)(3)(bpy)(MeOH)](PF(6)), bpy = 2.2'-bipyridine, with the TCNX ligands (TCNE = tetracyanoethene, TCNQ = 7,7,8,8-tetracyano-p-quinodimethane, and TCNB = 1,2,4,5-tetracyanobenzene) in CH(2)Cl(2) gave very different results. No reaction was observed with TCNB whereas TCNE produced very labile intermediates which converted under mild conditions to structurally characterized [(mu-CN)[fac-Re(CO)(3)(bpy)](2)](PF(6)) with an eclipsed conformation relative to the almost linear Re-CN-Re axis (Re-N(NC) 2.134(8) A, Re-C(CN) 2.098(8) A). With TCNQ, a stable tetranuclear complex [(mu(4)-TCNQ)[Re(CO)(3)(bpy)](4)](BF(4))(4) was obtained. Its structural, electrochemical, and spectroscopic analysis indicates only negligible charge transfer from the rhenium(I) centers to the extremely strong pi acceptor TCNQ. Evidence includes a calculated charge of only -0.09 for coordinated TCNQ according to the empirical structure/charge correlation of Kistenmacher, a high-energy nitrile stretching band nu(CN) = 2235 cm(-1), and unprecedented large anodic shifts >0.7 V of the reduction potentials. DFT calculations were used to confirm and explain the absence of electron delocalization from the electron-rich metals to the TCNQ acceptor bridge. Correspondingly, the X-band and high-frequency (285 GHz) EPR data (g = 2.007) as well as the IR and UV-vis-NIR spectroelectrochemical results (marginal nu(CO) shifts, TCNQ(*-) chromophore bands) support the almost exclusive confinement of the added electron in [(mu(4)-TCNQ)[Re(CO)(3)(bpy)](4)](3+) to the TCNQ bridge.

HIV/AIDS has disproportionately affected the Hispanic communities in the United States. Consequently, Hispanic communities at risk for HIV infection should be considered a high priority for prevention and education efforts. Although such efforts ideally consider variations across subpopulations, including differences in high-risk behaviors and routes of transmission by national origin, gender, and acculturation levels, relatively few studies of risk behavior have considered such differences. This paper reports on an interview-based study of HIV knowledge, risk behavior, and protective behaviors among a sample of 143 men and women of Mexican ethnicity in San Diego County, California and 189 men and women of Puerto Rican ethnicity in Cuyahoga County, Ohio. The authors' findings indicate that individuals who have been in the United States for longer periods of time and who are younger in age are at increased risk of HIV infection. Increased perceived risk may also be predictive of increased actual risk.

The Ru(2)(III,II) mixed-valent state is strongly stabilized in [(bpy)(2)Ru(mu-bttz)Ru(bpy)(2)](5+) (3(5+), bttz = 3,6-bis(2-thienyl)-1,2,4,5-tetrazine, as evident from lowered oxidation potentials and isolability, a strongly increased comproportionation constant K(c) = 10(16.6), and a high-energy intervalence charge transfer band at 10100 cm(-1). Curiously, no such effects were observed for the diosmium(III,II) analogue, whereas the related systems [(bpy)(2)M(mu-bmptz)M(bpy)(2)](5+), bmptz = 3,6-bis(4-methyl-2-pyridyl)-1,2,4,5-tetrazine, exhibit conventional behavior, i.e., a slightly higher K(c) value of the Os(2)(III,II) analogue. EPR signals were observed at 4 K for 3(5+) but not for the other mixed-valent species, and high-frequency (285 GHz) EPR was employed to study the diruthenium(II) radical complexes 2(3+) and 3(3+).

It has previously been shown that adrenalectomy (ADX) produces apoptosis in the granule cell of the dentate gyrus (DG), and that this effect is prevented by corticosterone replacement. Thus, we have investigated how this phenomenon takes place in rat hippocampus using in situ hybridization. The expression of the pro-apoptotic gene bax was measured in the pyramidal cell fields and in the DG. After 5 days of ADX, there was a significant increase in bax mRNA levels in the suprapyramidal layer of the DG, an effect prevented by corticosterone replacement. The mRNA of the anti-apoptotic bcl-2 gene was expressed in CA3 and DG. ADX increased bcl-2 mRNA levels, but only in the suprapyramidal layer of the DG, an effect that was prevented by corticosterone administration. It is concluded that the up-regulation of bax may explain the apoptosis observed in DG after ADX, while the bcl-2 induction may correspond to a compensatory mechanism protecting the cells from death.

The dinuclear radical anion complexes [(mu-L)[Re(CO)(3)Cl](2)](*)(-), L = 2,2'-azobispyridine (abpy) and 2,2'-azobis(5-chloropyrimidine) (abcp), were investigated by EPR at 9.5, 94, 230, and 285 GHz (abpy complex) and at 9.5 and 285 GHz (abcp complex). Whereas the X-band measurements yielded only the isotropic metal hyperfine coupling of the (185,187)Re isotopes, the high-frequency EPR experiments in glassy frozen CH(2)Cl(2)/toluene solution revealed the g components. Both the a((185,187)Re) value and the g anisotropy, g(1) - g(3), are larger for the abcp complex, which contains the better pi-accepting bridging ligand. Confirmation for this comes also from IR and UV/vis spectroscopy of the new [(mu-abcp)[Re(CO)(3)Cl](2)](o/)(*)(-)(/2)(-) redox system. The g values are reproduced reasonably well by density functional calculations which confirm higher metal participation at the singly occupied MO and therefore larger contributions from the metal atoms to the g anisotropy in abcp systems compared to abpy complexes. Additional calculations for a series of systems [(mu-abcp)[M(CO)(3)X](2)](*)(-) (M = Tc or Re and X = Cl, and X = F, Cl, or Br with M = Re) provided further insight into the relationship between spin density distribution and g anisotropy.

The complexes (bpym)PtCl(2) (1) and the new (micro-bpym)[PtCl(2)](2) (2), bpym = 2,2'-bipyrimidine, were synthesized and, in the case of 1, crystallized in solvent-free form for X-ray diffraction. The molecules 1 exhibit two different kinds of stacking motifs in the crystal with an interstack CH--N interaction. Complexes 1 and 2 were found to be sufficiently soluble for cyclic voltammetry, spectroscopy (absorption and emission), and spectroelectrochemical studies (UV-vis, EPR). As a result of single or double coordination of the strongly sigma-accepting [PtCl(2)] fragment to bpym, the paramagnetic anions 1(*)(-)() and 2(*)(-)() and the dianions 1(2-) and 2(2-) could be reversibly generated, despite the presence of metal-halide bonds. DFT calculations of A((195)Pt) and g tensor components confirm that the singly occupied MOs of the monoanionic species have mainly pi(bpym) character with nonnegligible platinum d orbital participation. The assignments of the electronic absorption and emission and resonance Raman spectra for both complexes are supported by DFT calculations.

The electron-transfer capacity of molecular rectangle ions [Pt(II)(4)(PEt(3))(8)(mu-anth(2-))(2)(mu-L)(2)](4+) with anth = anthracene-1,8-diyl and L = 4,4'-bipyridine (bp) or 1,2-bis(4-pyridyl)ethene (bpe) was investigated in acetonitrile and dichloromethane using cyclic voltammetry, EPR, and UV-vis-near-IR spectroelectrochemistry. The compounds can be reversibly reduced, first in a two-electron process and then via two closely separated one-electron steps. Oxidation was also possible at rather low potentials in a reversible two-electron step, followed by an electrochemically irreversible process. The spectroscopic results indicate reduction at the neutral acceptor ligands L and oxidation at the formally dianionic anthracene "clips". In contrast, the prototypical molecular square ([Pt(triphos)(mu-bp)](4))(8+) undergoes only irreversible reduction.

Purpose: To evaluate safety, predictability, efficacy, and stability of laser in situ keratomileusis (LASIK) for spherical hyperopia and hyperopia with astigmatism., Methods: In this retrospective study we analyzed the results of 23 eyes of 23 patients who had LASIK for spherical hyperopia (preoperative cylinder < or = 0.75 D) and 44 eyes of 44 patients who had LASIK for hyperopia with astigmatism; (Bausch & Lomb Hansatome microkeratome with a 180-microm plate and a suction ring for a 9.5-mm flap diameter; Asclepion-Meditec MEL 70 G-scan flying spot laser with a 1.8-mm Gaussian beam)., Results: In Group 1 (spherical hyperopia), mean preoperative spherical equivalent refraction was +4.88 +/- 2.13 D (range +2.13 to +9.63 D); in Group 2 (hyperopic astigmatism), +4.33 +/- 2.15 D (range +0.50 to +9.50 D). One year after LASIK, mean spherical equivalent refraction was +0.30 +/- 0.90 D (range -0.75 to +2.50 D) in Group 1 and +0.29 +/- 1.27 D (range -3.25 to +3.25 D) in Group 2. In Group 1, 78%, and in Group 2, 42% were within +/- 0.50 D. In Group 1, no eyes lost two or more lines, and one eye (6%) lost one line of best spectacle-corrected visual acuity at 1 year. In Group 2, one eye (4%) lost one line and one eye (4%) lost more than two lines at 1 year. Uncorrected visual acuity of 20/40 or better was achieved in 83% (Group 1) vs. 62% (Group 2) at 1 year; these values improved to 100% vs. 71% for corrections up to +6.00 D., Conclusions: LASIK with the Meditec MEL 70 G-Scan flying spot laser seemed to be safe and effective for hyperopia and hyperopia with astigmatism for corrections up to +6.00 D. Large flap diameters are necessary to avoid epithelial ingrowth.

Introduction: When evaluating angiographically marginal coronary stenoses (i.e. 40-70% reduction of the diameter of the arterial lumen) it is under certain conditions difficult to decide on their actual functional impact. Assessment of the fractional flow reserve (FFR) is a simple method based on assessment of intracoronary pressures during pharmacologically induced hyperaemia. For the severity of stenosis according to previous studies the liminal values is FFR lower than 0.75; furthermore it was proved that intervention of angiographically marginal stenoses with FFR values of 0.75 or more can be safely postponed., Objective: Test the safety of FFR examination and take in a group of patients with marginally severe stenosis further steps according to results of FFR assessment., Material and Methods: During the period from January to Juky 2000 FFR assessments were made in a total of 34 patients (11 women, 23 men, mean age 62 +/- 12 years) who suffered from marginal stenosis of some coronary vessel. The FFR examination took place under pharmacologically induced hyperaemia after intracoronary adenosine administration., Results: Measurements were made in a total of 41 stenoses. Only in two a value lower than 0.75 was found. In these patients coronary intervention was implemented; intervention was also made in two patients on account of technical problems and inconsistent results of FFR measurements. A FFR value of 0.75 or less was found in 37 stenoses (90%) and intervention was therefore postponed. Examination and the immediate subsequent course were without complications., Conclusion: According to initial experience FFR examination is a safe, simple and easily reproducible method. Based on the results of assessment and knowledge of the accomplished studies in the group of marginally significant stenoses in a great proportion of patients coronary intervention was postponed.

For bone development, remodeling, and repair; the recruitment of mesenchymal progenitor cells (MPC) and their differentiation to osteoblasts is mandatory. The process of migration is believed to be regulated in part by growth factors stored within the bone matrix and released by bone resorption. In this study, primary human MPCs and to osteoblasts differentiated progenitor cells were examined for chemotaxis in response to human basic fibroblast growth factor (rhbFGF), human transforming growth factor beta 1 (rhTGF-beta1), human platelet derived growth factor bb (rhPDGF-bb), human bone morphogenetic protein-2 (rhBMP-2), and recombinant bone morphogenetic protein-4 of Xenopus laevis (rxBMP-4) from 0.001 to 1.0 ng/ml each. The results of migration were expressed as a chemotactic index (CI). Migration of primary human progenitor cells was stimulated by rhBMP-2, rxBMP-4, and rhPDGF-bb in a dose-dependent manner. The increase of CI was up to 3.5-fold for rhBMP-2, 3.6-fold for rxBMP-4, and up to 22-fold for rhPDGF-bb, whereas rhTGF-beta1 and rhbFGF did not stimulate cell migration in the concentration range tested. In contrast differentiated progenitor cells behave similar to primary human osteoblasts. RhBMP-2, rhPDGF-bb, and rhTGF-beta1 stimulated the migration from 2.2 to 2.4-fold each, while rxBMP-4 and rhbFGF reached only a CI of 1.7-1.6. The effect of rhBMP-2, rxBMP-4, and rhPDGF-bb as chemoattractive proteins for primary human MPC, including the change in response to growth factors after differentiation suggests a functional role for recruitment of MPCs during bone development and remodeling, as well as fracture healing., (Copyright 2002 Wiley-Liss, Inc.)

The outbreak of foot-and-mouth disease in several member states of the European Union this year made the risks linked to this epidemic pretty clear to the public. In this connection, the possibility of vaccinations was controversially discussed not only among experts. Therefore it has to be taken into consideration that every kind of vaccination leads to economic consequences, which have to be taken into account when making such a decision. It is an illusion assuming that there will be a return to prophylactic vaccination. However in certain situations such emergency vaccination have to be available as an additional measure of control. Because of present decisions of the European Commission any consequences connected therewith are known. Thereby the EU regulations coincide with those of the Office International des Epizooties (OIE) and make the extent of restrictions after vaccination calculable. The assessment leads to the conclusion that preventive measures, rapid and successful eradication of FMD outbreaks as well as the option of emergency vaccination have to be followed as an overall conception.

Leukotriene B4 (LTB4) is a potent mediator of inflammation that recruits granulocytes to the site of injury during the inflammatory response. The biological activity of LTB4 is terminated by its metabolism into inactive metabolites. Recent studies have suggested that LTB4 may have additional activity as an endogenous ligand for the transcription factor peroxisome proliferator-activated receptor alpha (PPARalpha). Based on the data presented, a model was proposed in which LTB4 acts in a negative feedback manner by inducing the transcription of genes involved its own metabolism. In the present study the effect of PPARalpha activation on LTB4 metabolism was directly investigated. Primary cultures of rat hepatocytes were treated with LTB4 or the PPARalpha agonist WY-14,643, and LTB4 metabolism was assessed by measuring levels of LTB4 and the formation of LTB4 metabolites. In addition, the effect of PPARalpha activation on levels of acyl-CoA oxidase mRNA and expression of CYP4F proteins, which are specific omega-hydroxylases for LTB4, was determined. Treatment of hepatocytes with WY-14,643, but not LTB4, was found to increase acyl-CoA oxidase mRNA and enhance expression of rat hepatic CYP4F proteins and CYP4A1. Neither WY-14,643 nor LTB4 caused an increase of the basal levels of LTB4 metabolism, and no novel metabolites were observed. These results do not support the hypothesis that a pathway of negative feedback regulation of LTB4 metabolism involving PPARalpha exists in hepatocytes, because activation of PPARalpha by LTB4 or other PPARalpha agonists did not correlate with an increase in LTB4 metabolism.

Background: A national survey of the micronutrient status of preschool children in South Africa established that vitamin A deficiency is a significant public health problem, requiring urgent attention. A number of immediate and long-term interventions were recommended, including the introduction of a vitamin A supplementation programme and a food fortification programme., Objectives: The aim of the study was to assist in the development and implementation of a national vitamin A supplementation programme at primary health care facilities for mothers and children. This was achieved by determining the design, coverage and cost of a national primary health care facility vitamin A supplementation programme., Methods: Based on an extensive review of the literature, the main components of a primary health care facility vitamin A supplementation programme were identified. The annual, recurrent costs of each of the programme components were estimated for the nine provinces in South Africa. Immunisation coverage rates were used as a proxy for estimating the coverage of the programme., Results: The main components of the programme were identified as: promotion, training, purchase of vitamin A capsules, distribution of vitamin A capsules to primary health care facilities, distribution of capsules to the programme beneficiaries, and monitoring and evaluation. The programme would operate from primary health care facilities and would target all children between 6 and 24 months of age and newly delivered mothers. It was estimated that the programme would cover 74% of children and 95% of postpartum women nationally. The total annual, recurrent cost of the national programme was estimated at R16.4 million. The bulk of the costs would include personnel costs, comprising 68% of the total costs. Other costs included promotion (27%), vitamin A capsules (4%) and training (1%). The cost of the programme would vary significantly by province, but the provinces' average total cost per beneficiary would be similar., Conclusion: A primary health care facility vitamin A supplementation programme has been designed and accompanied by an estimated overall cost and coverage for implementation. The findings of the study showed that the programme would be financially feasible and would reach the majority of children under 24 months of age. It is recommended that further research be undertaken to extend the programme to the more 'hard to reach' population using other strategies such as mass immunisation campaigns.

The complexes [(DMA)Cu(PPh3)2](BF4) (1) (DMA = 1,3-dimethylalloxazine), [(DMA)Ru(bpy)2](PF6)2 (2), and (DMA)WO2Cl2 (3) were obtained as O4-N5-chelated species, as evident from an X-ray crystal structure analysis for 3 and from spectroscopy (NMR, IR, and UV-vis spectroelectrochemistry) for 1 and 2. The tungsten(VI) center in 3 has its oxide ligands in a cis/equatorial position and the chloride ligands in a trans/axial position; it also exhibits a relatively short bond to O4 (2.232(3) A) and a very long bond to N5 (2.462(3) A). Comparison with the new structurally characterized compound (BIK)WO2Cl2 (4) (BIK = bis(1-methylimidazol-2-yl)ketone), which has W-N bonds of about 2.30 A, confirms the unusual length of the W-N bond in 3, probably caused by repulsion between one of the oxo ligands and the peri-hydrogen atom (H6) of DMA. One-electron reduction of the complexes occurs reversibly at room temperature in THF (1, 2) or at 198 K in CH2Cl2 (3). EPR spectroscopy reveals that this process is ligand-centered for 1 and 2 but metal-centered for 3. Density functional methods and ab initio methodology are used to illustrate the correspondence in spin distribution between the radical anion pi systems of alloxazine and isoalloxazine ("flavosemiquinone").

Vitamin A deficiency (VAD) is a serious and widespread public health problem in the Philippines. Initiated in 1993, the Philippines National Vitamin A Supplementation Program (NVASP) is one of the oldest, most mature and comprehensive of its kind. This paper presents a cost-effectiveness and efficiency analysis of the NVASP and of a hypothetical program of vitamin A fortification of wheat flour that was conducted to inform policymakers as to how to modify the program. Employing a proxy effectiveness indicator of VAD--the intake of < 70% of the recommended daily allowance of vitamin A--in a series of simulations using individual child consumption data, the analysis finds that fortification is more efficient in reducing inadequate vitamin A intake (IVAI) compared to the NVASP. Due to the nature of food consumption patterns, however, fortification alone, is not enough. At what is regarded as the maximum politically acceptable fortification level, there will still be 2.2 million (29%) Filipino children aged 12-59 months who will have IVAI. An investigation of the cost and efficiency of geographically targeted supplementation programs reveals that maintaining a universal supplementation program in urban areas and, in rural areas, introducing a targeted program to only the poorest municipalities (where the prevalence of VAD is the highest) will provide a more acceptable public health policy response than fortification alone. Such a policy will reduce incremental direct Government expenditures on vitamin A programs by nearly 20% and will reduce the number of children with IVAI to 900,000 (12%) Filipino children. The paper describes the fortification and supplementation programs, and how their costs were estimated. Lessons for program designers and policymakers in other countries in which vitamin A deficiency constitutes a public health problem are also discussed.

Electrochemical reduction of the dinuclear [(eta 5-C5Me5)ClM(mu-L)MCl(eta 5-C5Me5)]2+ ions (M = Rh, Ir; L = 2,5-bis(1-phenyliminoethyl)pyrazine (bpip) and 2,5-bis[1-(2,6-dimethylphenyl)iminoethyl]pyrazine (bxip)) proceeds via the paramagnetic intermediates [(eta 5-C5Me5)ClM(mu-L)MCl(eta 5-C5Me5)]+ (L = bpip) or [(eta 5-C5Me5)M(mu-L)MCl(eta 5-C5Me5)]2+ (L = bxip) and [(eta 5-C5Me5)M(mu-L)M(eta 5-C5Me5)]+. Whereas the first is clearly a radical species with a small g anisotropy, the chloride-free cations are distinguished by structured intervalence charge transfer (IVCT) bands in the near-infrared region and by rhombic electron paramagnetic resonance features between g = 1.9 and g = 2.3, which suggests considerable metal participation at the singly occupied MO. Alternatives for the d configuration assignment and for the role of the bisbidentate-conjugated bridging ligands will be discussed. The main difference between bpip and bxip systems is the destabilization of the chloride-containing forms through the bxip ligand for reasons of steric interference.

Objective: The aim of this study was to determine the relationship between the parameters of individual serum lipids and the degree of intrauterine growth retardation (IUGR) of the fetus. The lipid levels were compared in fetuses with IUGR and in eutrophic fetuses and it was determined in which studied variable IUGR newborns differ from healthy newborns., Methods: The group under study consisted of 53 pregnant women in whom IUGR of the fetus was diagnosed by ultrasound during pregnancy. The control group consisted of 26 women who gave birth to eutrophic newborns. The cases in the control group were chosen by the method of matched control so that the results could be statistically evaluated in both groups at the same gestational age and at the same maternal age. In both groups blood samples from the umbilical cord were taken after delivery and the whole spectrum of lipid levels were evaluated (cholesterol-CH, triglycerides-TGA, high-density lipoprotein--HDL, low-density lipoprotein--LDL, Lp(a) lipoprotein, and apolipoproteins-ApoB, ApoAI, ApoE). The same parameters were evaluated in maternal and paternal blood samples. In several cases, intrauterine lipid levels of the fetus were determined by cordocentesis. The incidence of hyperlipoproteinemia in the families of both groups was surveyed., Setting: Department of Obstetrics and Gynaecology, 1st medical Faculty, Charles University, Prague., Results: There was a significant incidence of hyperlipoproteinemia in the families of the mothers in the group studied (chi-square test: p < 0.001). In the mothers of the groups studied, there were statistically significant higher levels of HDL, LDL, and Lp(a) in comparison to the mothers in the control group. A significant dependence was determined between the levels of ApoAI and Lp(a) of the mothers and newborns. In the regression analysis of the dependence of lipid levels on the birth weight of the newborns, a statistical correlation was determined for the values of ApoB and Lp(a)., Conclusion: The more increased the intrauterine growth retardation of the fetus and the lower its birth weight in relation to its gestational age, the higher its lipid levels, specifically apolipoproteins. Apolipoproteins are under genetic control and present a genetic risk for changes in the metabolism of cholesterol, hemocoagulation, and cardiovascular disease in adulthood.

Two molecule-bridged bis(tetracyanoiron) complexes [(NC)(4)Fe(BL)Fe(CN)(4)](n)()(-), BL = 2,2'-bipyrimidine (bpym) and 3,6-bis(2-pyridyl)-1,2,4,5-tetrazine (bptz), were studied by EPR, UV/vis/near-IR and IR spectroelectrochemistry (n = 2-5) in aprotic media. Following these results, the Fe(2)(2.5) formulation is the correct valence description for the metal centers in the bptz-bridged trianion (K(c) = 10(14.6) in CH(3)CN), whereas the localized Fe(III)/Fe(II) formulation is appropriate for the bpym-bridged system (K(c) = 10(5.4) in CH(3)CN and 10(6.4) in CH(2)Cl(2)). In contrast to common perception, the larger tetrazine-bridged system with the longer metal-metal distance exhibits much stronger metal-metal coupling than the bpym-bridged analogue, a consequence of the very low lying pi LUMO of tetrazines with high MO coefficients at the coordinating nitrogen centers.

A 3-wk period of stress promotes the development of ovarian cysts in rats apparently mediated by increased sympathetic nerve activity and ovarian steroid secretion. After 11 wk of stress, these parameters are indistinguishable from nonstressed control rats. To study adrenal contribution, we adrenalectomized rats and studied the effect of 3-wk of cold/restraint stress (1.5 h/d) on them compared to intact animals. Adrenalectomy (ADX) increased ovarian norepinephrine (NE) release, the content of beta-adrenergic receptors (betaAR) and basal, but not isoproterenol (Iso)-induced, androgen secretion. Stress to intact animals increased NE release, decreased betaAR content, and Iso-induced, but not basal, androgen secretion from the ovary. ADX did not modify the response to stress. We propose a tonic inhibition by the adrenal gland on nerve activity of ovarian nerves. Stress overrides this inhibitory effect, and nerve activity downregulates betaAR, decreasing ovarian steroid secretion.

Ignorance about the costs, case loads and case mixes of different hospitals within the public health system constitutes an important obstacle to reforming health care spending in many developing countries. National (tertiary) hospitals generally receive significantly larger budgets, per patient, than lower-level (district) hospitals. One reason for these differential allocations is the widely held belief that national hospitals treat persons with more difficult illnesses and persons who are more severely ill than do other, non-national, hospitals. This belief is but a presumption and one that warrants investigation. This paper analyzes expenditures among public hospitals in El Salvador over a 12-year period to address this question. While controlling for patient morbidity, outputs and other characteristics, district hospitals are found to be substantially underfunded relative to national hospitals. Four policy options to redress this situation are examined.

Leptin is a protein hormone produced predominantly by adipocytes. Serum leptin concentrations in healthy individuals positively correlate with the body fat content and body mass index, i.e. they are higher in obese than in lean subjects. The relations between serum leptin concentration and serum lipids and lipoproteins is not yet clear. The aim of our study was to compare serum leptin concentrations in 22 randomly selected patients with untreated combined hyperlipidemia and 19 healthy control subjects matched for age and the body mass index. The relationship was studied between serum leptin concentrations and serum lipids (total, HDL, LDL cholesterol and triglycerides) and lipoproteins (lipoprotein (a), apolipoprotein B). It was found that serum leptin levels in patients with combined hyperlipidemia did not significantly differ from those of control subjects (6.69+/-4.3 vs 5.78+/-3.2 ng.ml(-1)). Serum leptin concentrations in both groups correlated positively with the body mass index. The relationship between leptin concentrations and lipid or lipoprotein levels found in any of the studied groups was not statistically significant. We conclude that serum leptin concentrations in patients with combined hyperlipidemia as well as in healthy control subjects reflect the body fat content and have no significant relation to serum lipids or lipoproteins.

Forty-three patients with trigeminal neuralgia (TN) unresponsive to pharmacologic treatment and/or prior invasive procedures underwent stereotactic radiosurgery with the Gamma Knife (GK). Outcome was evaluated by a standardized questionnaire mailed to each patient. The mean follow-up was 9 months. Fifteen patients (35%) reported no trigeminal pain and were no longer taking medication. Three patients (7%) experienced occasional pain, but were no longer taking medication. In 15 patients (35%), pain improved and was adequately controlled by medication, often in lower dosages than preoperatively. Pain was reduced in 9 patients (21%), but their symptoms were still inadequately controlled by drug therapy, and 1 patient (2%) reported no pain relief after treatment. Three patients (7%) described new facial numbness, but in none was this bothersome. GK radiosurgery for TN appears to have minimal morbidity, although the success rate may be slightly lower than that of other operative procedures. More patients and longer follow-up are needed before drawing final conclusions regarding efficacy and complications., (Copyright 2000 S. Karger AG, Basel)

A controlled multiplex polymerase chain reaction (PCR) for the detection of Clostridium(C.) perfringens enterotoxin gene (cpe) was established and compared with an in vitro antigenic detection method. Thecpe PCR and the classical method of electric immunodiffusion gave identical results. The predicted specific amplicon of the cpe gene was generated from all of the tested enterotoxigenic C. perfringens strains. In contrast, cultures of any other Clostridium species tested by PCR were negative (100% sensitivity, 100% specificity). Addition of an alphatoxin (plc) gene specific PCR as an in process control reaction was performed in order to prevent false negative PCR results. The PCR detection limit was 0.5 ng of genomic C. perfringens DNA per ml of bouillon culture. By contaminating minced meat with C. perfringens reference strains, the multiplex PCR was established as a tool for routine diagnostic laboratories. The detection limit was approximately 3.0x10(5)C. perfringens cells per gram meat. The results demonstrate the multiplex PCR as an easy, specific, sensitive and time saving diagnostic procedure. Application of this improved method should enhance the knowledge concerning epidemiological aspects of food borne diseases caused by enterotoxigenic C. perfringens., (Copyright 1998 Academic Press)

The rhenium(I) compounds [(NwedgeN)Re(CO)(3)(MQ)](PF(6))(2) (NwedgeN = 2,2'-bipyridine (bpy), 2,2'-bipyrimidine (bpym), 3,3'-bipyridazine (bpdz), or 1,4,7,10-tetraazaphenanthrene (tap) and MQ(+) = N-methyl-4,4'-bipyridinium) undergo four one-electron reduction steps which could be analyzed using cyclic voltammetry, EPR, IR, and UV/vis spectroelectrochemistry. Due to the rather low-lying pi orbital of tap, the corresponding compound shows electron uptake by NwedgeN each time before MQ(+) is reduced. The opposite is observed for the complexes of the other chelate ligands NwedgeN, however, and the pi(NwedgeN) orbital aproaches the pi(MQ(+)) level in the order bpy < bpym < bpdz. Remarkably, the reduction processes of MQ(+) and bpdz in [(bpdz)Re(CO)(3)(MQ)](PF(6))(2) are separated by only 74 mV as deduced from IR spectroelectrochemical analysis. On reduction of the related compound [(bpy)Re(CO)(3)(mpz)](PF(6))(2) (mpz(+) = N-methylpyrazinium), the first two electrons are added to the axial ligand which has a lower-lying pi orbital than MQ(+) and cannot undergo intramolecular twisting.

The effect of exogenous leukotriene B4 (LTB4) on opsonized zymosan-stimulated human neutrophil formation of 5-lipoxygenase products and arachidonic acid release was directly assessed using reverse-phase HPLC/tandem mass spectrometric methods for quantitation. Stable isotopically labeled LTB4, [1,2-13C2]LTB4, caused a dose-dependent inhibition of LTB4 production in isolated human neutrophils with significant inhibition (60 +/- 7% of control levels) when 0.12 nM [13C2]LTB4 was present. Production of 5-hydroxy-6,8,11,14-eicosatetraenoic acid and release of free arachidonic acid were also dose-dependently inhibited by exogenous LTB4. Metabolites of LTB4, 20-hydroxy-LTB4 and 3(S)-hydroxy-LTB4, also significantly reduced LTB4 production to levels as low as 10 +/- 6% and 10 +/- 7% of control levels, respectively, when present exogenously at 10 nM. Exogenous 5-hydroxy-6,8,11,14-eicosatetraenoic acid at concentrations as high as 10 nM produced no significant reduction in LTB4 biosynthesis during zymosan-stimulated human neutrophil production of LTB4. The inhibitory effect of LTB4 could be partially reversed by the LTB4 receptor antagonist U 75302. Furthermore, an alternative stimulus, N-formyl-methionyl-leucyl-phenylalanine (100 nM), did not inhibit the production of LTB4 in opsonized zymosan-stimulated human neutrophils. These results suggest that activation of the LTB4 receptor on the human neutrophil during phagocytosis limits the ultimate biosynthesis of LTB4. This autocrine effect is opposite to that observed when neutrophils have much of the signal transduction pathways bypassed when stimulated with calcium ionophore A23187 or treated with exogenous free arachidonic acid.

Activation of the sympathetic innervation precedes the induction of polycystic ovaries in rats given estradiol valerate (EV). The mechanism of induction by EV may thus involve both direct and neurogenic components. We tested this hypothesis using a combined cold and restraint stress to induce an increase in sympathetic tone, including that of the ovarian sympathetic nerves. Three weeks after the start of stress we found: 1. An increase in the content of norepinephrine (NE) in the celiac ganglion. 2. An increase in the release of NE from the ovary. 3. An unchanged NE uptake by the ovary. 4. An unchanged content of NE in the ovary. The ovarian content of neuropeptide Y (NPY) (colocalized with NE) was significantly decreased. These results suggest that NE synthesis and its secretion are increased during this period and correlate with the increase in secretion of androgens and estradiol, the development of precystic follicles, and a decrease in the ovulatory rate. After 11 wk, NE release had returned to control values, whereas the ovarian NE content had risen significantly, suggesting a maintained high rate of NE synthesis. In the ovary, NPY contents, steroid secretion, morphology, and ovulation had returned to the control state. These results suggest the participation of an extraovarian factor that might act locally to control the release of NE from the ovary, and further support the hypothesis that increased sympathetic activity plays a role in the development and maintenance of ovarian cysts.

Stakeholders formulating policies on national health insurance (NHI) in the Eastern Caribbean have circled the abstract concept called NHI like the proverbial blind men explaining the elephant. Definitions of NHI have shifted depending on their perspectives and philosophical leanings, their understanding of the issues, and their degree of influence on the process. Based on NHI feasibility studies, market research, and stakeholder analysis conducted in five countries, this article analyses the policy formulation stage of NHI development in these tiny countries. Given the level of economic development and the existing administrative capacity of the governments, this 'phase one' NHI could be a pragmatic first step in introducing a health insurance component into the social security systems of the countries, and gradually reforming other aspects of the health sector. The article is structured around key questions which help to define the positions and relationships of key stakeholders, and then evaluate NHI plans in terms of economic viability, equity, administrative feasibility and efficiency, cost containment incentives, and political palatability. These are the elements that--in combination with economic and political context--will determine the success or failure of NHI in the Eastern Caribbean.

This article presents a step-down cost analysis using secondary data sources from 26 Bangladesh non-government organizations (NGOs) providing family planning services under a US Agency for International Development-funded umbrella organization. The unit costs of the NGOs' Maternal-Child Health (MCH) clinics and community-based distribution (CBD) systems were calculated and found to be minimally different. Several simulations were conducted to investigate the impact of alternative cost-reduction measures. The more general financial analysis proved more insightful than the unit cost analysis in terms of identifying means by which to improve the efficiency of the family planning operations of these NGOs. The analysis revealed that 56 per cent of total expenditures in the two-tiered umbrella's organizational structure are incurred in management operations and overheads. Of the remaining 44 per cent of project expenditures, 39 per cent is spent on the CBD program and 5 per cent on the MCH clinics. Within the CBD program, most resources are spent providing 4 million contacts (two-thirds of the annual total) which do not involve contraceptive re-supply. The clinics devote more resources to providing MCH services than to providing family planning services. The findings suggest that significant savings could be generated by containing administrative costs, improving operational efficiency, and reducing unnecessary or redundant fieldworker contacts. The magnitude of the potential savings raises a fundamental question about the continued viability and sustainability of this supply-driven CBD strategy.

The oxidation and reduction behavior of complexes [(mpz)M(CN)(5)](2)(-) between the group 8 pentacyanometalates(II) and the N-methylpyrazinium ion mpz(+) was studied using spectroelectrochemical techniques (UV/vis/NIR, IR, EPR) in nonaqueous and, in part, aqueous media. As a further source of information on the electronic structure, we studied the variable solvatochromism of MLCT absorption bands in the precursor ions [(mpz)M(CN)(5)](2)(-). The mpz-centered one-electron reduction showed a tendency for concomitant loss of cyanide (EC process) to yield ions [(mpz)M(CN)(4)](2)(-), the lability increasing in the order M = Os << Ru < Fe. In contrast to the EPR spectra obtained from reduction with S(2)O(4)(2)(-) in aqueous media, which showed no evidence for close mpz(*)/metal association, the intra muros electrolysis experiments in DMSO or acetonitrile yielded the following results: The EPR spectrum that was previously assigned to [(mpz)Fe(CN)(5)](3)(-) is now ascribed to [(mpz)Fe(CN)(4)](2)(-). Whereas the dissociatively inert osmium radical complex [(mpz)Os(CN)(5)](3)(-) is distinguished by a broad EPR signal with a rather large value g(iso) = 2.0157, the EPR spectrum of [(mpz)Ru(CN)(4)](3)(-) reveals well-resolved separate coupling with the (99)Ru and (101)Ru isotopes in natural abundance. Spectroelectrochemistry and reactivity patterns of the complex ions [(mpz)M(CN)(5)](2)(-) are reminiscent of results for corresponding nitrosyl complexes [(NO)M(CN)(5)](2)(-), which suggests that the mpz(+)/mpz(*) ligand redox pair can function as an organic analogue of the NO(+)/NO(*) redox system.

A 54-year-old man had a slowly progressive bilateral brachial plexopathy 17 months after surgery and radiation therapy for a stage IV supraglottic carcinoma. MR imaging at presentation showed a symmetric pattern of parascalene and interscalene hyperintense signal on T2-weighted images and after contrast enhancement. Although hyperintense signal has been more often associated with recurrent tumor than with delayed radiation injury or fibrosis, the location and pattern of the signal abnormalities suggested a diagnosis of radiation-induced plexopathy. This diagnosis was confirmed by the relative stability of the neurologic and MR findings 30 months after treatment.

1,4-Bis(2,6-dimethylphenyl)-1,4-diaza-1,3-butadiene (dab) forms the structurally characterized iridium(III) complex [CpIrCl(dab)](PF(6)): C(28)H(35)ClF(6)IrN(2)P, orthorhombic, space group Pnma, a = 16.187(2) Å, b = 15.823(2) Å, c = 11.677(1) Å, V = 2990.8(6) Å(3), Z = 4, and R = 0.0588. On reaction with NaBH(3)CN this compound does not form an iridium(III) hydride but the coordinatively unsaturated reduced product CpIr(dab): C(28)H(35)IrN(2), monoclinic, space group P2(1)/n, a = 8.484(2) Å, b = 14.535(3) Å, c = 20.956(4) Å, beta = 98.88(3) degrees, V = 2553.2(9) Å(3), Z = 4, and R = 0.0586. The inverted relation d(CC) (=1.334(15) Å) < d(CN) (=1.379(13) and 1.366(14) Å) in the dab ligand of CpIr(dab) suggests that the reduction has occurred primarily at that ligand to form an ene-1,2-diamido/iridium(III) moiety or, alternatively, a six-pi-electron metallaheteroaromatic system. Ab initio pseudopotential calculations of model complexes [CpIr(HNCHCHNH)](0/2+) support this description of the bonding.

The purpose of the study presented in this paper was to estimate, using secondary sources of data, the cost and effectiveness of three programs to combat vitamin A deficiency in Guatemala-the national sugar fortification program, a targeted capsules distribution program and the promotion of home food production combined with nutrition education and to draw conclusions concerning priorities for Guatemala. Data on the costs and coverage were collected from implementing agencies in Guatemala. Coverage data were converted into a common set of impact indicators. Sensitivity analyses were conducted on variables whose precise value was uncertain. Potential impacts of improvements in program performance operations were also explored. The analysis found the cost per high-risk person achieving adequate vitamin A to be US $0.98 for fortification, US $1.68-1.86 for capsule distribution and US $3.10-4.16 for food production/education. Fortification is the most efficient option if vitamin A levels in sugar are maintained at reasonable levels. Where fortified sugar is not consumed and vitamin A deficiency is highly prevalent, small-scale, targeted, complementary interventions such as capsules and food production education may be appropriate for sustained broader impacts.

Pseudoxanthoma elasticum is an inherited disorder of connective tissue that is characterized by calcification of elastic fibers with associated abnormalities of the skin, ocular, and cardiovascular systems. The genetic defect causing pseudoxanthoma elasticum has not been determined and the diagnosis relies on clinical recognition of skin lesions and histologic demonstration of calcification of elastic fibers that are clumped and fragmented in the dermis. The role of connective tissue components in the etiology of pseudoxanthoma elasticum is reviewed and includes changes in collagen, elastin, glycosaminoglycans, fibronectin, microfibrillar proteins, modifying enzymes of extracellular matrix proteins, fibroblasts, and fibrillins.

With Leksell Gamma Knife stereotactic radiosurgery, the dose distribution delivered by a specific helmet can be assumed to remain as a fixed-dose distribution when the shot is moved to different locations within the predefined dose calculation matrix. The convolution theorem may be implemented to take advantage of this fact for fast dose computation and plan construction. Using this technique, the shot spatial arrangement is formulated as a convolution kernel, which is theoretically a three-dimensional multi-delta function. The dose distribution is computed by the convolution of this single-shot dose distribution with the shot convolution kernel. To determine the shot arrangement, an ideal dose distribution is generated based upon the target structure. Deconvolution is then applied to find the convolution kernel which best fits the proposed ideal dose distribution. The primary task of this presentation is to focus on and describe in detail the dose computation using the convolution theorem.

Purpose: Solid state diodes and/or thermoluminescent dosimeters (TLDs) are often used to measure scattered radiation doses to critical organs immediately adjacent to radiation field sites. The energy-dependent response of these commonly used in vivo dosimeters sometimes makes the interpretation of measured values uncertain. This study investigates scattered radiation arising from the collimator jaws of linear accelerators and the treatment head of a cobalt-60 teletherapy unit., Methods and Materials: A thin window Markus-type parallel-plate ionization chamber placed in a polystyrene phantom was employed to document the magnitude, energy composition, and sources of scattered radiation at surfaces near radiation fields. Measurements were taken both with and without additional phantom material covering the ionization chamber, as well as with various distances between the ionization chamber and edges of the radiation fields tested., Results: Data was collected, analyzed and compared for treatment units produced by different manufacturers. It was found that the magnitude of scattered radiation to surfaces immediately adjacent to radiation fields ranged from 1% to 15% of the maximum dose along the beam central axis. These values showed a strong dependence upon distance from the edge of the radiation field, beam energy, collimator setting (field size), and the presence of externally mounted accessories. Teletherapy unit differences due to manufacturing firm origins were found to only slightly affect scattered radiation magnitude, while the orientation of upper and lower collimator jaws had absolutely no effect., Conclusions: Percent depth dose curves of scattered radiation were obtained and analyzed. The shapes of these depth dose curves suggest the presence of complex energy spectra from secondary electrons and scattered x-rays. Because of the presence of these complex energy spectra in areas immediately adjacent to radiation fields, caution should be observed when interpreting patient doses near radiation fields, if dose values have been measured in vivo using thermoluminescent dosimeters (TLDs) or solid state diodes. Many of these on-patient dosimetry devices are strongly energy dependent and may demonstrate large over- or under-responses in areas dominated by scattered radiation. The results of this study, thus, suggest that ionization chambers are preferred for determination of scattered radiation doses in such regions.

The trisomy-16 (TS16) mouse is considered to be a model of human trisomy 21 (Down syndrome) because of genetic homology between mouse chromosome 16 and human chromosome 21. We examined cholinergic function of brain and spinal cord tissue and in cultured neurons from TS16 mouse compared with that of age matched controls. Mean acetylcholinesterase activity in both tissue types did not differ between trisomic and control conditions. Acetylcholine (ACh) synthesis, measured as choline O-acetyltratransferase (acetyl-CoA) activity, was reduced to 67% of control in TS16 brain but not in TS16 spinal cord. Steady-state accumulation of ACh precursor, [3H]choline, was measured in primary cell cultures. Steady-state choline uptake was reduced to 35% and to 61% in neurons of TS16 brain and spinal cord, respectively, when compared with controls. Kinetics experiments in TS16 brain cells showed a 50% reduction of the maximal velocity of choline uptake when compared to controls. Further, the ACh release induced by KCl depolarization in TS16 spinal cord neurons did not differ from control neurons but was reduced in TS16 brain neurons. This effect cannot be explained solely by a reduction in ACh synthesis. The results indicate that the TS16 condition in mice significantly modified the cholinergic function in brain, and to a lesser degree in spinal cord, suggesting that the higher gene dosage inherent to the trisomic condition affects cholinergic neurons in different regions of the central nervous system in a differential fashion.

Since the early 1980s, the Ministries of Health of most Developing Countries have been plagued by significant and persistent resource shortages. One response of many Third World countries to this health financing crisis has been to turn to user fees. This article presents a case study of the evolution of public health care system fees in El Salvador in the decade of the 1980s. Since 1980 falling levels of real funding of the Ministry of Health of El Salvador have resulted in falling supplies of drugs, materials and equipment throughout the public health system, and have contributed to declining utilization levels of public health facilities. Local public health providers and their community health boards (patronatos) have responded to this crisis by creatively institutionalizing decentralized, revolving accounts based on 'voluntary' user fees for ambulatory care, collected and retained at individual facilities. This article describes the legal foundations, organization, functioning, incentive structures, financial performance, and the institutional development of El Salvador's local user fee systems.

Assessment of electron beam energy and its long term stability is part of standard quality assurance practice in radiation oncology. Conventional depth-ionization or depth-film density measurements are time consuming both in terms of data acquisition and analysis. A procedure is described utilizing ionization measurements at two energy specific depths. It is based on a linear relationship between electron beam energy and its practical range. Energy shifts within the range covered by the two measurement depths are easily resolved. Within a range of +/- 0.50 MeV (+/- 1.30 MeV) around the established mean incident energy of 5.48 MeV (20.39 MeV), the method accuracy is better than 0.10 MeV.

Although high dose-rate brachytherapy with a single, rapidly moving radiation source is becoming a common treatment modality, a suitable formalism for determination of the dose delivered by a moving radiation source has not yet been developed. At present, brachytherapy software simulates high dose-rate treatments using only a series of stationary sources, and consequently fails to account for the dose component delivered while the source is in motion. We now describe a practical model for determination of the true, total dose administered. The algorithm calculates both the dose delivered while the source is in motion within and outside of the implanted volume (dynamic component), and the dose delivered while the source is stationary at a series of fixed dwell points. It is shown that the dynamic dose element cannot be ignored because it always increases the dose at the prescription points and, in addition, distorts the dose distribution within and outside of the irradiated volume. Failure to account for the dynamic dose component results in dosimetric errors that range from significant (> 10%) to negligible (< 1%), depending on the prescribed dose, source activity, and source speed as defined by the implant geometry.

The primary mechanism of cyanide (CN) intoxication is the inhibition of metabolism in the central nervous system. We determined the effects of CN on several biochemical processes in neuroblastoma x glioma hybrid NG108-15 cells, which possess numerous neuronal properties. These cells were not sensitive to a high concentration (1 mM) of NaCN, but became sensitive in the presence of the anaerobic glycolysis inhibitors sodium iodoacetate (IA) and 2-deoxyglucose (2-DG):cellular metabolic processes (e.g., DNA, RNA and protein synthesis) decreased to about 40% of control due to treatment with 0.5 mM NaCN + 0.05 mM IA and 0.1 mM NaCN + 20 mM 2-DG. ATP in cells exposed to 0.01 or 0.1 mM NaCN + 20 mM 2-DG was reduced 75% and 100% respectively within one min. Pretreatment of cells with the CN antidote cobalt (II) chloride (CoCl2) (0.06-0.18 mM) for 5 min prevented the depression of both [3H]leucine incorporation and ATP synthesis due to 1 mM NaCN + 20 mM 2-DG in a concentration-dependent manner. A proposed CN antidote alpha-ketoglutaric acid (disodium salt) also prevented the depression of cellular metabolism due to NaCN plus 2-DG. These results indicate that blocking anaerobic glycolysis makes NG108-15 cells sensitive to a low concentration of CN. Thus NG108-15 cells should be useful to study the mechanisms of neurotoxicity of CN and to test antidotes.