Immuno-EM using colloidal metal nanoparticles and electron spectroscopic imaging for co-localization at high spatial resolution.

Multiple-labelling immuno-EM is a powerful tool for localizing and co-localizing different antigens simultaneously in cells and tissues at high spatial resolution. Commonly used labels for this purpose are differently sized gold spheres. A comparison of results obtained with differently sized markers is often difficult, because the diameters of markers influence labelling efficiency. In the current study, we investigate a method for high-resolution multiple-labelling immuno-EM, using equally sized colloidal markers made of different metals. Energy filtering transmission electron microscopy is used to differentiate particles based on elemental composition. The labels consist of colloidal gold, palladium and platinum-core gold-shell particles of approximately 6 nm in diameter, which are conjugated to different primary antibodies. Applicability of the electron spectroscopic imaging, methodology is demonstrated by labelling of actin, alpha-actinin and myosin on ultra-thin cryosections of skeletal muscle tissue.

Hazards of succinylcholine administration during electrotherapy.

We describe prolonged apnea following electrotherapy in a patient who was also being treated with a topical organophosphate anticholinesterase, ecothiophate iodide (phospholine iodide), for glaucoma. The increased duration of action of succinylcholine resulted from low levels of serum cholinesterase that had been caused by the organophosphate. Attention is called to other drugs that directly or indirectly (by lowering serum cholinesterase) interact with succinylcholine chloride resulting in prolonged apnea. Other potential hazards of succinylcholine administration, such as hyperkalemia and cardiac arrhythmias, are also discussed.

Psychiatric illness in homicide victims.

The authors studied the demographic characteristics and history of psychiatric treatment of 214 homicide victims and 67 suicide victims. Thirty-two (15%) of the homicide victims and 12 (18%) of the suicide victims had a record of psychiatric care; these rates were higher than the treatment rate of the general population. The authors suggest that there may be a connection between the occurrence of homicide and the increased frequency of psychiatric disorders among victims of this crime.

Ascorbic acid uptake and metabolism by corneal endothelium.

Ascorbic acid is concentrated in various ocular compartments where it is thought to protect diurnal animal species against damaging effects of ultraviolet radiation. The authors evaluated the possibility that corneal endothelial cells have specific transport and/or metabolic properties that deliver ascorbic acid to the stroma. Bovine corneal endothelial cells were grown to confluence in multiple-well plates. Individual groups of cells (approximately 10(4)) were then incubated at various times at 34 degrees C in a physiologic buffer that contained a 10 microM level of 14C-labeled ascorbic acid or the oxidized product, dehydro-L-ascorbic acid. Endothelial cells take up dehydro-L-ascorbic acid at least seven times as rapidly as they take up ascorbic acid. After 30 sec of incubation with 14C-dehydro-L-ascorbic acid, most of the label accumulated in the cell is in the reduced form. Uptake is inhibited by cyanide and iodoacetamide but is unaffected by ouabain. Exposure of cultured cells to various intermediates in the energy metabolism pathways reduced uptake of ascorbic acid but had a minor effect on uptake of the oxidized molecule. These results suggest that the cornea has transport and metabolic capacity to extract dehydro-L-ascorbic acid from aqueous humor and reduce it, thus providing a source of ascorbic acid for corneal protection. This also would maintain "total" ascorbic acid of aqueous humor in the reduced state.

Dosage schedule and plasma levels of doxepin and desmethyldoxepin.

Plasma levels of doxepin and its metabolite desmethyldoxepin were determined in 7 depressed patients treated with doxepin hydrochloride in 3 divided doses at 1000, 1600, and 2200 hours (t.i.d.), and repeated after changing the dosage schedule to a single daily bedtime (h.s.) dose at 2200 hours. Doxepin and its metabolite were measured at 9000, 1200, 1500, and 1800 hours. None of the individual patients showed clinically significant changes in their plasma concentration of tricyclic antidepressant on the 2 dosage schedules. No difference in the clinical condition of the patients was detected on the 2 dosage schedules using the Zung Self Rating Depression Scale, however patients experienced more morning sedation while on the single h.s. dosage. This study provides pharmacological support for the prescription of doxepin on a once daily basis.

Imipramine and desipramine plasma levels: relationship to dosage schedule and sampling time.

Tricyclic antidepressant plasma levels were determined after administration if imipramine (11 patients) and desipramine (ten patients) as a single daily bedtime dose or in divided doses. Plasma levels of the tricyclics were relatively stable on both dosage schedules due to the long plasma half-lives of these drugs. No difference was found between the two dosage schedules and the therapeutic effectiveness or the severity of side effects. The majority of patients preferred the single dose schedule. These findings support the use of a single daily dose of imipramine and desipramine.

[Compiling the data of vitrectomy patients. Waiting list organization and quality assurance]. / Datenerfassung von Vitrektomiepatienten. Wartelistenverwaltung und Qualitätssicherung.

Owing to an increasing frequency of ophthalmological operations and the necessity of shortening the patient's stay in hospital surgical scheduling and data compilation in ophthalmology can only be managed by means of electronic data processing. We present a computer program that compiles a waiting list for vitrectomies and organizes the scheduling of operations. On each patient's first visit a standardized form containing the essential clinical findings if filled out. On the basis of these data the computer, using a specially designed algorithm places the patient in an appropriate position on the waiting list and eventually informs him or her of the date of the operation. In a similar manner the postoperative findings and the results of the follow-up examinations are documented. The system allows effective scheduling based on the urgency of the operation and the prognosis of the disease. Furthermore, it facilitates prospective recording of the clinical course and the treatment outcome. The use of electronic data processing does not only mean an improvement in clinical organization and, especially, in surgical planning, but also facilitates a quick evaluation of clinical studies with a large number of patients.

X-ray diffuse scattering measurements of nucleation dynamics at femtosecond resolution.

Femtosecond time-resolved small and wide angle x-ray diffuse scattering techniques are applied to investigate the ultrafast nucleation processes that occur during the ablation process in semiconducting materials. Following intense optical excitation, a transient liquid state of high compressibility characterized by large-amplitude density fluctuations is observed and the buildup of these fluctuations is measured in real time. Small-angle scattering measurements reveal snapshots of the spontaneous nucleation of nanoscale voids within a metastable liquid and support theoretical predictions of the ablation process.

Carrier-density-dependent lattice stability in InSb.

The ultrafast decay of the x-ray diffraction intensity following laser excitation of an InSb crystal has been utilized to observe carrier dependent changes in the potential energy surface. For the first time, an abrupt carrier dependent onset for potential energy surface softening and the appearance of accelerated atomic disordering for a very high average carrier density have been observed. Inertial dynamics dominate the early stages of crystal disordering for a wide range of carrier densities between the onset of crystal softening and the appearance of accelerated atomic disordering.

Breakdown of K selection in 178Hf.

Coulomb activation of the four quasiparticle Kpi=16+ 178Hf isomer (t1/2=31 y) has led to the measurement of a set of Elamda matrix elements coupling the isomer band to the ground band. The present data combined with earlier 178 Hf Coulomb excitation data have probed the components in the wave functions and revealed the onset and saturation of K mixing in low-K bands, whereas the mixing is negligible in the high-K bands. The implications can be applied to other quadrupole-deformed nuclei.

Collectivity and configuration mixing in 186,188Pb and 194Po.

Lifetimes of prolate intruder states in 186Pb and oblate intruder states in 194Po have been determined by employing, for the first time, the recoil-decay tagging technique in recoil distance Doppler-shift lifetime measurements. In addition, lifetime measurements of prolate states in 188Pb up to the 8+ state were carried out using the recoil-gating method. The B(E2) values have been deduced from which deformation parameters |beta2|=0.29(5) and |beta2|=0.17(3) for the prolate and the oblate bands, respectively, have been extracted. The results also shed new light on the mixing between different shapes.

Notes on epidemiology of homicide in an urban area.

Over the past 30 years, there was a slow but steady increase of the homicide rate in the United States. The increase was faster in the urban areas. In St. Louis, Missouri, the rate had increased from 7/100 000 in 1943 to 33/100 000 in 1973. The development of meaningful preventive measures depends upon repeated epidemiologic investigations to determine the changes in patterns of crime to see if our approach to the problem is still adequate to meet the need. The police records of 214 homicide victims in the city of St. Louis during 1973 were examined. Mean age of the victims was 35 years. Eighty-five per cent of them were men and 81% were black. There are 2 distinctly different profiles of homicide victims, "younger" under 30 years old, and "older" 30 years old and over. "Young" victims had a mean age of 21 years. They were more likely to be black, killed after an argument over money or property, or while committing a crime, and killed by a gun. There were more black victims killed by other blacks and the murderer was usually older (mean age 26 years). These homicides were less frequently victim-precipitated, killed by a relative or friend, or while drinking. "Older" victims had a mean age of 49 years. Among them there were more whites, more victim-precipitated and more victims drank prior to their death, while the murderer was usually younger (mean age 35 years).

A rating scale for mania: reliability, validity and sensitivity.

An eleven item clinician-administered Mania Rating Scale (MRS) is introduced, and its reliability, validity and sensitivity are examined. There was a high correlation between the scores of two independent clinicians on both the total score (0.93) and the individual item scores (0.66 to 0.92). The MRS score correlated highly with an independent global rating, and with scores of two other mania rating scales administered concurrently. The score also correlated with the number of days of subsequent stay in hospital. It was able to differentiate statistically patients before and after two weeks of treatment and to distinguish levels of severity based on the global rating.

Cost analysis in the Department of Veterans Affairs: consensus and future directions.

OBJECTIVES: In 1997, the Management Decision and Research Center of the Department of Veterans Affairs convened cost experts and health economists in a working meeting. Its goal was to provide consensus guidelines for conducting cost analyses in managed care systems, such as VA, that do not have encounter-level cost data or that do not prepare itemized patient bills. The impetus for the meeting was that too often computer-based cost data were proposed or used in studies that were inappropriate for the question being addressed. There was also a sense that often great effort was being expended by VA health economists "reinventing the wheel" in developing new cost components for each study. METHODS: A group of 45 VA and non-VA health economists, health researchers, and policy-makers attended a 2 day working meeting organized around a series of case vignettes to identify areas of consensus, controversy, and gaps in knowledge. RESULTS: Consensus emerged in the following four areas: (1) Cost Methods. A "hybrid model" was identified as the current standard of cost analysis in VA and entails mixing "micro-costing" primary data collection and "gross-cost" computer-based methods to reflect resource-use variations that are essential to the research question. (2) Cost Infrastructure. VA is developing a new, but unevaluated, costing system that could allow for computer-based cost analyses at much finer levels of detail than is currently possible. (3) Data Quality. Ongoing data validation of existing and developing cost databases is needed, especially concerning interfacility variation. (4) Dissemination. A new cost data center was recommended to provide training, information dissemination, and coordination. CONCLUSIONS: Consensus was reached about the hybrid model as the current paradigm for cost analysis in systems like VA.

Use of pharmacy computer prescription database to access hypertensive patients for mailed survey research.

OBJECTIVE: To evaluate the use of a pharmacy computer prescription database (PCPD) to identify and sample hypertensive patients outside of their treatment setting for mailed, self-administered survey research comparing the presence and lack of participation incentives and mailed follow-up reminders. SETTING: Two independent, privately owned, free-standing community pharmacies. PARTICIPANTS: A total of 735 individuals identified from a PCPD search who had been prescribed at least 1 of 130 PCPD medications potentially used in hypertensive therapy. METHODS: PCPD was searched by the pharmacist/owner per protocol; participants were sent an individually addressed cover letter on pharmacy letterhead signed by the pharmacist that requested voluntary anonymous completion of an enclosed self-administered, quality-of-life opinion survey; the first search used no incentive or follow-up; the second search used an incentive and mailed a follow-up reminder. Research protocol followed published ethics guidelines. RESULTS: There was a mean 84% return with incentive and follow-up strategies compared with a mean 25% return without strategies (p < 0.01) for all drug groups between searches; no statistical difference in response was shown between the same drug groups (alpha 1-blockers, calcium-channel blockers, and centrally acting alpha 2-agonists) within searches. CONCLUSIONS: Acceptable response rates (74-93% return) can be obtained with traditional follow-up mailed incentives, prescription issuance within 6 months, incentives to both hypertensive and nonhypertensive responders, and sampling strategies within potential drug groups. Methodology can be adapted to other populations by alternative drug sampling strategies.

Fetal alcohol exposure alters neurosteroid modulation of hippocampal N-methyl-D-aspartate receptors.

The actions of ethanol on brain ligand-gated ion channels have important roles in the pathophysiology of alcohol-related neurodevelopmental disorders and fetal alcohol syndrome. Studies have shown that N-methyl-d-aspartate (NMDA) receptors are among the ligand-gated ion channels affected by prenatal ethanol exposure. We exposed pregnant dams to an ethanol-containing liquid diet that results in blood ethanol levels near the legal intoxication limit in most states (0.08%). Primary cultures of hippocampal neurons were prepared from the neonatal offspring of these dams, and NMDA receptor function was assessed by patch clamp electrophysiological techniques after 6-7 days in culture in ethanol-free media. Unexpectedly, we did not detect any changes in hippocampal NMDA receptor function at either the whole-cell or single-channel levels. However, we determined that fetal alcohol exposure alters the actions of the neurosteroids pregnenolone sulfate and pregnenolone hemisuccinate, which potentiate NMDA receptor function. Western immunoblot analyses demonstrated that this alteration is not due to a change in the expression levels of NMDA receptor subunits. Importantly, in utero ethanol exposure did not affect the actions of neurosteroids that inhibit NMDA receptor function. Moreover, the actions of pregnenolone sulfate on type A gamma-aminobutyric acid and non-NMDA receptor function were unaltered by ethanol exposure in utero, which suggests that the alteration is specific to NMDA receptors. These findings are significant because they provide, at least in part, a plausible mechanistic explanation for the alterations in the behavioral responses to neurosteroids found in neonatal rats prenatally exposed to ethanol and to other forms of maternal stress (Zimmerberg, B., and McDonald, B. C. (1996) Pharmacol. Biochem. Behav. 55, 541-547).

Signature for vibrational to rotational evolution along the yrast line.

We present a simple method for discerning the evolution from vibrational to rotational structure in nuclei as a function of spin. The prescription is applied to the yrast cascades in the A approximately 110 region and a clear transition from vibrational to rotational motion is found.