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Hand hygiene (HH) performance on entering intensive care units (ICUs) is commonly accepted but often inadequately performed. We developed a simple, inexpensive module that connects touchless dispensers of alcohol sanitiser (TDAS) to the automatic doors of a paediatric ICU, and assessed the impact of this intervention on HH compliance of hospital staff and visitors. A prospective observational study was conducted over a 3-week period prior to the intervention, followed by a 4-week period post intervention. HH performance was monitored by a research assistant whose office location enabled direct and video-assisted observation of the ICU entrance. A total of 609 entries to the ICU was recorded. Overall HH performance was 46.9% (92/196) before and 98.5% (406/413) after the intervention. Our findings suggest that HH performance on entering an ICU can be improved via a mechanism that makes operation of an automatic door dependent on use of a TDAS system, and thus contribute to infection control.

The diagnosis of recurrent aspiration in young children is problematic because there is no specific gold standard test to be used. In the present work, normal saline or a suspension of white polystyrene microspheres in normal saline was instilled into hamsters' trachea (n = 42), and bronchoalveolar lavage (BAL) cytology, microsphere index (total microspheres/100 macrophages), and lung histology were followed for 90 d. Naive animals (n = 6) had no tracheal instillation. On Days 1, 3, 10, 32, 60, and 90 after tracheal instillation, animals were killed (saline-instilled animals, n = 3; and microsphere-instilled animals, n = 4), and BAL was performed. There was a marked inflammatory response in BAL on Day 1 after tracheal instillation of saline or microsphere suspension. White microspheres were clearly identified within alveolar macrophages in all studied days. Microsphere numbers showed a 50% disappearance rate of 10 d. A mild peribronchial inflammation was noted in lung histology only on Day 1 after instillation. Microspheres were not detected in extrapulmonary organs. We conclude that polystyrene microspheres instilled in hamsters' trachea can be easily identified in BAL macrophages for as long as 3 mo and could potentially be used as a sensitive, specific, and stable marker for the diagnosis of aspiration.

Familial Mediterranean fever (FMF) is an inherited disease whose manifestations are acute but reversible attacks of sterile inflammation affecting synovial and serosal spaces. The FMF gene (MEFV) was recently cloned, and it codes for a protein (pyrin/marenostrin) homologous to known nuclear factors. We previously reported the deficient activity of a C5a/interleukin (IL)–8 inhibitor, a physiologic regulator of inflammatory processes, in FMF serosal and synovial fluids. We now describe the concomitant expression ofMEFV and C5a/IL-8–inhibitor activity in primary cultures of human fibroblasts. Fibroblasts grown from synovial and peritoneal tissues displayed C5a/IL-8–inhibitor activity that could be further induced with phorbol myristate acetate (PMA) and IL-1β. Very low levels of chemotactic inhibitor were evident in skin fibroblast cultures or in peritoneal and skin fibroblasts obtained from FMF patients. MEFV was expressed in peritoneal and skin fibroblasts at a lower level than in neutrophils and could be further induced by PMA and IL-1β. In the FMF cultures, the MEFV transcript carried the M694V mutation, consistent with the genetic defect found in patients with this disease. MEFV was also expressed in other cell lines that do not produce C5a/IL-8 inhibitor. These findings suggest that human primary fibroblast cultures express MEFV and produce C5a/IL-8–inhibitor activity. The interrelationship between pyrin, the MEFV product, and the C5a/IL-8 inhibitor requires further investigation.

In order to identify genes specific for the sensory neurons of Aplysia, a miniaturized differential screening method based on the polymerase chain reaction and applicable to small amounts of tissue was used. One messenger RNA was isolated that is expressed in every mechanoreceptor sensory cluster of the Aplysia central nervous system. This messenger RNA encodes a peptide that seems to function as an inhibitory cotransmitter. The peptide selectively inhibits certain postsynaptic cells but not others and thereby allows the sensory neurons to achieve target-specific synaptic actions.

Nervous tissue of the marine mollusc, Aplysia californica, generates arachidonic acid metabolites in response to neurotransmitters such as histamine or FMRFamide. In addition, identified neurons of Aplysia respond to the pharmacologic application of some of these products, particularly those of the 12-lipoxygenase pathway. We investigated the chirality of the initial Aplysia 12-lipoxygenase product, 12-HPETE, in preparation for more detailed metabolic studies and for the analysis of the physiological activity of the endogenous lipid. Neural homogenates and intact ganglia exclusively generate 12(S)-HPETE as do the better characterized mammalian lipoxygenases. The direct application of 12(S)-HPETE to cultured sensory neurons induced a hyperpolarization which averaged 2.6 mV. We did not find any difference between the response to the naturally-occurring 12(S)-HPETE and its diastereomer, 12(R)-HPETE which is not generated in Aplysia. Both isomers were significantly more effective than 15(S)-HPETE. In contrast, 12(S)-HPETE, but not 12(R)-HPETE, was a potent modulator of the action of the molluscan neuropeptide, FMRFamide. Prior application of 12(S)-HPETE to cultured sensory neurons increased the subsequent response to a submaximal dose of FMRFamide by 60%. On the other hand, 12(R)-HPETE reduced the subsequent response to the peptide by 30%. The lack of stereospecificity in the direct effect of the lipids differs markedly from their stereospecific effects as modulators of FMRFamide action. This suggests that there may be an important neurophysiologic role for these lipid modulators which is distinct from their direct effects, and also indicates that there are multiple sites and mechanisms by which lipid hydroperoxides act on neurons in Aplysia.

We have examined the relationships between the modulation of transmitter release and of specific ionic currents by membrane potential in the cholinergic interneuron L10 of the abdominal ganglion of Aplysia californica . The presynaptic cell body was voltage-clamped under various pharmacological conditions and transmitter release from the terminals was assayed simultaneously by recording the synaptic potentials in the postsynaptic cell. When cell L10 was voltage-clamped from a holding potential of -60 mV in the presence of tetrodotoxin, graded transmitter release was evoked by depolarizing command pulses in the membrane voltage range (-35 mV to + 10 mV) in which the Ca 2+ current was also increasing. Depolarizing the holding potential of L10 results in increased transmitter output. Two ionic mechanisms contribute to this form of plasticity. First, depolarization inactivates some K + channels so that depolarizing command pulses recruit a smaller K + current. In unclamped cells the decreased K + conductance causes spike-broadening and increased influx of Ca 2+ during each spike. Second, small depolarizations around resting potential (-55 mV to -35 mV) activate a steady-state Ca 2+ current that also contributes to the modulation of transmitter release, because, even with most presynaptic K + currents blocked pharmacologically, depolarizing the holding potential still increases transmitter release. In contrast to the steady-state Ca 2+ current, the transient inward Ca 2+ current evoked by depolarizing clamp steps is relatively unchanged from various holding potentials.

A subcellular fraction (P3) from Aplysia is enriched in synaptosomes (Chin et al., 1988) and is capable of accumulating 5-HT and choline. At an external 3H-5-HT concentration of 1.8 microM, the P3 fraction took up 0.12 nmol/mg protein in 30 min. Uptake was dependent on external Na+. Electron microscopic autoradiography showed that much of the accumulated 3H-5-HT is localized to synaptosomes. At 0.5 microM 3H- choline, P3 took up 0.11 nmol/mg protein in 30 min and converted 40% to 3H-ACh. This synaptosomal fraction was also capable of releasing transmitter. After 3H-5-HT or 3H-choline was taken up, P3 released about 5% of the total radioactive transmitter in a Ca2+-dependent manner during a 30 sec exposure to a depolarizing concentration of K+ (100 mM). Identified, prelabeled synaptosomes were prepared by injecting 3H-choline into the large cholinergic neuron L10. The abdominal ganglia containing the injected cells were then fractionated, yielding synaptosomes containing radioactivity derived from L10. After this synaptosomal fraction was exposed to high K+, 2% of the radioactivity was released in a Ca2+-dependent manner. This release was completely blocked by 0.1 mM histamine, a modulatory transmitter that has previously been shown to cause presynaptic inhibition in L10.

By voltage clamping presynaptic cell L10 and using pharmacologic separation techniques, we have analyzed the specific ionic currents in the presynaptic cell that correlate with presynaptic inhibition while assaying transmitter release with intracellular recordings from postsynaptic cells. We have found that presynaptic inhibition can be elicited in conditions in which the Na+ and the various K+ channels are pharmacologically blocked and depolarizing current pulses produce only an inward Ca2+ current. Both inward currents and tail currents at and above the K+ reversal potential were always less inward during presynaptic inhibition. The changes in conductance associated with presynaptic inhibition were voltage sensitive and paralleled the voltage sensitivity of the Ca2+ channel. We therefore conclude that presynaptic inhibition is caused by a direct transmitter-mediated decreased of presynaptic Ca2+-channel conductance.

AT THE END of 1945 the corporate universe was characterized by a low level of capital assets relative to sales and a high degree of liquidity. The decade ending in 1955 was noteworthy for the high absolute level of investment in plant, equipment, and inventory. Corporations experienced no great financing difficulties in carrying out their expansion program; interest rates did not rise sharply during the period. The bulk of corporate investment was financed from internal sources of funds-retained profits and depreciation allowanceswith internal sources more important in the first half of the ten-year period. The relationship between internal and external financing was primarily dependent on cyclical variations in business activity. In periods of rising business activity short-term borrowing and new security issues were utilized to supplement internal funds. In periods of declining economic activity long-term financing through security issues was continued on a reduced scale and short-term bank debt was reduced. Over the decade ending in 1955 there was an increasing trend toward long-term securities issued to finance investment in plant, equipment, and inventories. All bonds outstanding for nonfinancial corporations more than doubled from $23 billion at the end of 1945 to $54 billion at the end of 1955. There was some evidence to suggest that reduction in spreads between stock and bond yields encouraged stock financing in the latter years of the period. The most striking phenomenon in the long-term debt market was the precipitous decline in the importance of individuals as holders of corporate bonds. In less than twenty years individuals' holdings of outstanding corporate bonds fell from two-thirds to about one

The interest in capital equipment analysis that has been evident in the business literature of the past five years is the product of numerous social, economic, and business developments of the postwar period. No conclusive listing of these developments can be attempted here. However, four should be mentioned which are of particular importance in this search for a more systematic method for discovering, evaluating, and selecting investment opportunities. These are: (1) the high level of capital outlays (in absolute terms); (2) the growth in the size of business firms; (3) the delegation of responsibility for initiating recommendations from top management to the profit center, which has been part of the general movement toward decentralization; and (4) the growing use of “scientific management” in the operations of the business firm.

12-Hydroperoxy-5,8,10,14-eicosatetraenoic acid (12-HPETE), a lipoxygenase product, simulates the synaptic responses produced by the modulatory transmitter, histamine, and the neuroactive peptide, Phe-Met-Arg-Phe-amide (FMRFamide), in identified neurons of the marine mollusk, Aplysia californica (Piomelli, D., Shapiro, E., Feinmark, S. J., and Schwartz, J. H. (1987) J. Neurosci. 7, 3675-3886; Shapiro, E., Piomelli, D., Feinmark, S., Vogel, S., Chin, G., and Schwartz, J. H. (1988) Cold Spring Harbor Symp. Quant. Biol. 53, in press). The 12-lipoxygenase pathway has not yet been fully characterized, but 12-HPETE is known to be metabolized further. We therefore began to search for other metabolites in order to investigate whether the actions of 12-HPETE might require its conversion to other active products. Here we report the identification of 12-keto-5,8,10,14-eicosatetraenoic acid (12-KETE), a metabolite of 12-HPETE formed by Aplysia nervous tissue. This product was identified in incubations of the tissue with arachidonic acid using high performance liquid chromatography, UV spectrometry, and gas chromatography/mass spectrometry. [3H]12-KETE was formed from endogenous lipid stores in nervous tissue, labeled by incubation with [3H]arachidonic acid, when stimulated by application of histamine. In L14 and L10 cells, identified neurons in the abdominal ganglion, applications of 12-KETE elicit changes in membrane potential similar to those evoked by histamine. 12(S)-Hydroxy-5,8,10,14-eicosatetraenoic acid, another metabolite of 12-HPETE, is inactive. These results support the hypothesis that 12-HPETE and its metabolite, 12-KETE, participate in transduction of histamine responses in Aplysia neurons.

Release of arachidonic acid from membrane phospholipids is receptor- mediated and might generate second messengers in neurons. We tested this idea using the simple nervous system of the marine mollusk, Aplysia californica. Aplysia neural components metabolize arachidonic acid through lipoxygenase and cyclo-oxygenase pathways. We identified 2 major lipoxygenase products, 12- and 5-hydroxyeicosatetraenoic acids (12-HETE and 5-HETE), and 2 cyclo-oxygenase products, PGE2 and PGF2 alpha. These metabolites of arachidonic acid are formed in synaptosomes, as well as in identified nerve cell bodies, indicating that both lipoxygenase and cyclo-oxygenase pathways are active within neurons. Application of the modulatory neurotransmitter histamine to cerebral ganglia that had been labeled with 3H-arachidonic acid induced the formation of 3H-12-HETE. This response was inhibited by the histamine antagonist cimetidine. Furthermore, release of radioactive 5- HETE and 12-HETE was observed after intracellular stimulation of the histaminergic cell C2 in cerebral ganglia labeled with 3H-arachidonic acid. Cimetidine also inhibited this response. Application of serotonin or stimulation of the giant serotonergic cell (GCN) in the cerebral ganglion did not cause detectable amounts of the labeled eicosanoids to be released. We found that intracellular stimulation of putative histaminergic neurons in the L32 cluster of the abdominal ganglion, which produces presynaptic inhibition in L10 neurons, also elicited the release of 3H-12-HETE and 3H-PGE2. Thus, for the first time we provide evidence that synaptic stimulation promotes turnover of arachidonic acid in neurons. We suggest that metabolites of arachidonic acid are likely to participate in some postsynaptic responses to histamine and may be second messengers for presynaptic inhibition.

The lipoxygenase product 12-hydroperoxy-5,8,10,14-eicosatetraenoic acid (12-HPETE), stimulates the synaptic response produced by the modulatory transmitter histamine and the neuroactive peptide Phe-Met-Arg-Phe-amide (FMRFamide) in identified neurons of the marine mollusk Aplysia californica. The 12-lipoxygenase pathway has not yet been fully characterized, but 12-HPETE is known to be metabolized further. Therefore, we began to search for other metabolites in order to investigate whether the actions of 12-HPETE might require its conversion to other active products. We have identified 12-keto-5,8,10,14-eicosatetraenoic acid (12-KETE) as a metabolite of 12-HPETE formed by Aplysia nervous tissue. 12-KETE was identified in incubations of the tissue with arachidonic acid using HPLC, UV spectrometry, and gas-chromatography/mass spectrometry. [3H]12-KETE is formed from endogenous lipid stores in nervous tissue, labeled with [3H]arachidonic acid upon stimulation by application of histamine. In L14 and L10 cells, identified neurons in the abdominal ganglion, applications of 12-KETE elicit changes in membrane potential similar to those evoked by histamine. Another metabolite of 12-HPETE, 12(s)-hydroxy-5,8,10,14-eicosatetraenoic acid [12(S)-HETE], is inactive. These results support the hypothesis that 12-HPETE and its metabolite, 12-KETE, participate in transduction of histamine responses in Aplysia neurons.

In Aplysia neural tissue, the release and metabolism of arachidonic acid are stimulated by histamine or by activation of the identified L32 nerve cell circuit of the abdominal ganglion. Previously we found that histamine and intracellular stimulation of L32 cells, which are putatively histaminergic neurons, cause the production of 12-hydroxy-5,8,10,14-icosatetraenoic acid (12-HETE), a product of the 12-lipoxygenase pathway formed through 12-hydroperoxy-5,8,10,14-icosatetraenoic acid (12-HPETE). 12-HPETE, but not 12(S)-HETE, mimics the dual-action response of L14 ink motor neurons to histamine and stimulation of L32. 12-HPETE can also be further metabolized to 8-hydroxy-11,12-epoxy-5,9,14-icosatrienoic acid (8-HEpETE) which was identified by HPLC, enzymatic hydrolysis, and GC/MS. Production of 8-HEpETE is specific, as its positional isomer 10-hydroxy-11,12-epoxy-5,8,14-icosatrienoic acid is not formed after physiologic stimulation. 8-HEpETE can elicit the late component (hyperpolarization) of the dual-action response in L14 cells, suggesting that it may be a second messenger in Aplysia.

We prepared and characterized subcellular membrane fractions from the CNS of Aplysia californica that are enriched in isolated nerve terminals (synaptosomes). Ganglia were homogenized in 1.1 M sucrose and fractionated on a 2-step sucrose gradient, yielding 50 micrograms protein/animal in the synaptosomal fraction (P3), which was enriched 3- fold in plasma membrane as compared with the initial homogenate. Quantitative morphometry of electron micrographs revealed that P3 contained 25% intact synaptosomes, a 5-fold enrichment over the homogenate. Although fractionation on a 5-step sucrose gradient reduced the yield of protein in the synaptosomal fraction to 40 micrograms/animal, this fraction (the 0.35 M/0.75 M interface) was more enriched in plasma membrane than P3 and was less contaminated by lysosomes and free mitochondria. By electron microscopy, the 0.35 M/0.75 M interface contained up to 50% synaptosomes. Synaptosomal fractions contained cAMP-, Ca2+/calmodulin-, and Ca2+/phospholipid- dependent protein kinase activities and were enriched in a Mr 40,000 pertussis toxin substrate, Gi/o. In the accompanying paper, we show that these synaptosomes retain the ability to release transmitters.

* Research Assistant in Statistics, The School of Business, The University of Chicago. ** Associate Professor of Finance, The School of Business, The University of Chicago. ***Member of the Ohio Bar. 1. This excludes unlisted stock which is traded over-the-counter. 2. U.S. Treas. Reg. 105, ?81.10(c) (1944); U.S. Treas. Reg. 108, ?86.19(c) (1943). There is no assurance the market would have absorbed additional shares on a given date at then prevailing prices; the market might have been broken under the weight of further offerings. The judge-made blockage rule is a response to this difficulty. This rule, applicable only in respect of large blocks of stock, Mott v. Commissioner, 139 F.2d 317 (6th Cir. 1943), permits the stock to be valued at the lowerthan-market figure which could have been realized, according to the testimony of experts, by means of a special offering or secondary distribution, that is, off-theexchange merchandising by specialists over a period of time. Havemeyer v. United States, 59 F. Supp. 537 (Ct. Cl. 1949), cert. denied, 326 U.S. 759 (1945); Groff v. Munford, 150 F.2d 825 (2d Cir. 1945); Thomas A. Standish, 8 T.C. 1204 (1947), Acq. 1947-2 CuM. BULL. 4. Thus blockage substitutes unverifiable estimates for the objective criterion of actual sales or bona fide bid and asked prices. But, in contrast with the procedure followed in valuing closely-held stocks, the issue is sharply defined (What could have been realized by means of a special offering or secondary distribution?) and relevant considerations are correspondingly delimited. The regulations themselves leave the door open for escape in hard cases from the objective market-price-equals-value rule: "In cases in which it is established that the value per bond or share of any security determined on the basis of selling or bid and asked prices as herein provided does not reflect the fair market value thereof, then some reasonable modification of such basis or other relevant facts and elements of value shall be considered in determining fair market value." U.S. Treas. Reg. 105, ? 81.10(c) (1944); U.S. Treas. Reg. 108, ?86.19(c) (1943). MONTGOMERY, FEDERAL TAXES-ESTATES, TRUSTS AND GIFTs 626 (1949-1950), lists 16 cases in which the value of stock was determined to be less than the quoted market price. Such cases, however, may fairly be considered exceptions and, aside from cases involving very large blocks of stock, the courts are not easily persuaded to depart from market quotations. E.g., Estate of Caroline McCulloch Spencer, 5 T.C. 904, Aca. 1946-1 CUM. BULL. 4. (166)

There are several important suppliers of short-term funds' in our financial system. The means used by small concerns to secure short-term financing are associated closely enough with the institutional practice of these lenders that, in large part, the two must be considered together. Therefore, this discussion concentrates upon the financial relationships between small businesses and (i) the commercial banking system, (2) other financial intermediaries, (3) business firms in their lending activities, and (4) specialized financing institutions.

TN THE period I929-40 consumer debt rose with increases in consumer disposable income and decreased when disposable income fell. The level of consumer debt relative to income tended to be higher during years of decreasing income than during years of rising income.2 The years since I939 were characterized by sustained high levels of economic activity. National income rose from $70.8 billion in I939 to $i6i.o billion in I945.3 Despite the past relationship between consumer disposable income and consumer debt, the volume of consumer debt fell from $8.o billion in I939 to $6.6 at the end of I945.4 The destruction of the past relationship between disposable income and consumer debt was due to two main factors; the curtailment of the production of consumers durable goods early in I942 and the restriction upon the extension of consumer credit first imposed in August, I94I, and made more stringent during the warA The state of Wisconsin shared in the wartime prosperity in the United States. Income payments in that state rose from $I.5 billion in I939 to $3.4 billion in 1945.6 The total volume of consumer debt outstanding in Wisconsin fell during this period for the same reasons that explain the fall in the national totals. It is the purpose of this paper to study the manner in which credit unions, one of the institutions extending credit to consumers, adapted themselves to the imposed restrictions upon their lending during the war period. Where data are available, references are also made to I946.7

r 9H E maximum rate of charge which the state permits licensed . personal finance companies to charge is often criticized as excessive. Lenders engaged in the business defend these rates on the ground that the high costs of extending small loans necessitate legal rates which are sufficiently high to induce capital to enter into the industry and engage in business under the licensing and regulation of the state. The lenders contend that if the maximum rate of charge is not high enough to permit profitable investment of capital, the business will disappear entirely, thus cutting off these credit facilities from the low-income groups which normally make up the market for personal finance loans,3 or it will be conducted illegally at still higher rates of charge by persons who are willing to risk criminal prosecution for violating the usury statutes.4 Since its inception the industry has been subjected to a great deal of pressure to reduce the maximum rates of charge permitted by the usury statutes or other regulatory legislation. In part, the pressure for rate reduction emanates from well-meaning people who are unfortunately suffering from a cultural lag. Accepting the widespread notion that any charge in excess of 6 per cent per annum is usurious, they consider a rate of 3 per cent per month on unpaid balances or 36 per cent per annum on the average outstanding balance as an immoral exaction. Actually, these companies operate under a statute specifically exempting them from the usury law and maximum rates charged are established by law.A The personal finance companies are credit agencies having relatively high costs of lending, and it is unlikely that they could operate under the ordinary usury statutes. Where small-loan laws do not exist, this type of credit-small loans to low-income borrowers-is either not available or available only from loan sharks.6 Another source of pressure for rate reductions comes from the illegal lenders. Their business is seriously limited by the competition of personal finance companies, and, in order to remove this competition, they exert pressure to lower the maximum rate of charge permitted to personal finance companies to a point where these lenders can no longer continue in business at a profit. Once the personal finance companies are driven I The author is indebted to Dr. Ralph A. Young, director, Financial Research Project, National Bureau of Economic Research, for his painstaking criticism of and contributions to the content of this article. However, all opinions expressed are solely those of the author.