Rapid point-of-care testing for SARS-CoV-2 in a community screening setting shows low sensitivity.

OBJECTIVE: With the current SARS-CoV2 outbreak, countless tests need to be performed on potential symptomatic individuals, contacts and travellers. The gold standard is a quantitative polymerase chain reaction (qPCR)-based system taking several hours to confirm positivity. For effective public health containment measures, this time span is too long. We therefore evaluated a rapid test in a high-prevalence community setting. STUDY DESIGN: Thirty-nine randomly selected individuals at a COVID-19 screening centre were simultaneously tested via qPCR and a rapid test. Ten previously diagnosed individuals with known SARS-CoV-2 infection were also analysed. METHODS: The evaluated rapid test is an IgG/IgM-based test for SARS-CoV-2 with a time to result of 20 min. Two drops of blood are needed for the test performance. RESULTS: Of 49 individuals, 22 tested positive by repeated qPCR. In contrast, the rapid test detected only eight of those positive correctly (sensitivity: 36.4%). Of the 27 qPCR-negative individuals, 24 were detected correctly (specificity: 88.9%). CONCLUSION: Given the low sensitivity, we recommend not to rely on an antibody-based rapid test for public health measures such as community screenings.

MRSA infections among patients in the emergency department: a European multicentre study.

BACKGROUND: MRSA is a therapeutic concern worldwide, and a major agent of community-acquired skin and soft tissue infections (CA-SSTIs). While the US epidemiology of MRSA in CA-SSTIs is well described and reports the high prevalence of the USA300 clone, data on the European situation are lacking. OBJECTIVES: To determine the prevalence and clonal characteristics of MRSA in CA-SSTIs in seven European emergency departments. PATIENTS AND METHODS: From April to June 2015, patients presenting to the tertiary hospital emergency department with a Staphylococcus aureus CA-SSTI were prospectively enrolled. S. aureus isolates were characterized by antimicrobial susceptibility testing, detection of Panton-Valentine leucocidin encoding genes and spa-typing, MLST and/or DNA microarray. RESULTS: Two-hundred and five cases of S. aureus-associated CA-SSTIs were included, comprising folliculitis, furuncles, abscesses, paronychia, impetigo, carbuncles and cellulitis. Of the 205 cases, we report an MRSA prevalence rate of 15.1%, with a north (0%) to south (29%) increasing gradient. Fifty-one isolates were Panton-Valentine leucocidin-positive (24.9%), whether MSSA or MRSA, with a heterogeneous distribution between countries. Clonal distribution of MSSA and MRSA showed high diversity, with no predominant circulating clone and no archetypical USA300 CA-MRSA clone. CONCLUSIONS: This original prospective multicentre study highlights stark differences in European MRSA epidemiology compared with the USA, and that the USA300 CA-MRSA clone is not predominant among community-infected patients in Europe.

Distinct activation of primary human BDCA1(+) dendritic cells upon interaction with stressed or infected ß cells.

Derailment of immune responses can lead to autoimmune type 1 diabetes, and this can be accelerated or even induced by local stress caused by inflammation or infection. Dendritic cells (DCs) shape both innate and adaptive immune responses. Here, we report on the responses of naturally occurring human myeloid BDCA1(+) DCs towards differentially stressed pancreatic ß cells. Our data show that BDCA1(+) DCs in human pancreas-draining lymph node (pdLN) suspensions and blood-derived BDCA1(+) DCs both effectively engulf ß cells, thus mimicking physiological conditions. Upon uptake of enterovirus-infected, but not mock-infected cells, BDCA1(+) DCs induced interferon (IFN)-α/ß responses, co-stimulatory molecules and proinflammatory cytokines and chemokines. Notably, induction of stress in ß cells by ultraviolet irradiation, culture in serum-free medium or cytokine-induced stress did not provoke strong DC activation, despite efficient phagocytosis. DC activation correlated with the amount of virus used to infect ß cells and required RNA within virally infected cells. DCs encountering enterovirus-infected ß cells, but not those incubated with mock-infected or stressed ß cells, suppressed T helper type 2 (Th2) cytokines and variably induced IFN-γ in allogeneic mixed lymphocyte reaction (MLR). Thus, stressed ß cells have little effect on human BDCA1(+) DC activation and function, while enterovirus-infected ß cells impact these cells significantly, which could help to explain their role in development of autoimmune diabetes in individuals at risk.

Blending of reactive prepolymers to control the morphology and polarity of polyglycidol based microgels.

The compartmentalization of microgels is a challenging task for synthetic polymer chemistry. Although the complexation with low molecular weight compounds or the use of microfluidic techniques offer attractive possibilities for other length scales, it is difficult to implement compartments in the mesoscale range of 10-100 nm. Herein we show how simple blending of reactive prepolymers is suitable to design new microgel morphologies with tailored compartments. We use poly(EEGE)-block-poly(AGE) as crosslinkable, pro-hydrophilic prepolymer in blends with varying amounts of crosslinkable, yet hydrophobic poly(THF-stat-AllylEHO) or inert and hydrophobic polystyrene, and crosslink the allyl functional prepolymer(s) in a thiol-ene click-type reaction after miniemulsification. Our strategy shows how arrested versus free nanophase separation can be used to control easily the morphology and polarity of microgel particles.

Hepatitis C treatment uptake and adherence among injecting drug users in the Czech Republic.

BACKGROUND: Injecting drug users (IDUs) represent a major subpopulation of hepatitis C virus (HCV)-infected people in developed countries. Yet their uptake to treatment is generally low despite well-documented effectiveness of HCV treatment among former and active IDUs. The present study represents the first attempt to describe the HCV treatment coverage among IDUs and identify factors that affect treatment uptake in the Czech Republic. METHODS: From January to March 2011, a questionnaire survey was conducted among viral hepatitis treatment centres in the Czech Republic. RESULTS: From a total of 76 identified hepatitis treatment centres existing in the country, 39 provided HCV treatment to (mainly former or abstaining) IDUs in 2010. Most clinicians reported being cautious in initiating HCV treatment in IDUs. Abstinence, a screening phase before treatment initiation, opioid substitution treatment and an external evaluation by a specialist were often prerequisites for skrting treatment. However, HCV treatment centres rarely provided drug-use specific services. Financial constraints were also reported, further limiting the inclusion of IDUs into treatment, as non-users are widely preferred to active drug users. Clinicians reported no difference in treatment uptake and adherence between drug users and non-users, nor between opioid and methamphetamine users. CONCLUSION: A number of system- and provider-related factors limit HCV treatment in IDUs in the Czech Republic, despite permissive national clinical guidelines. Targeting these factors is crucial to reduce HCV prevalence at population level.

[Mental health of children, adolescents and young adults--part 1: prevalence, illness persistence, adversities, service use, treatment delay and consequences]. / Die psychische Gesundheit von Kindern, Jugendlichen und jungen Erwachsenen--Teil 1: Häufigkeit, Störungspersistenz, Belastungsfaktoren, Service-Inanspruchnahme und Behandlungsverzögerung mit Konsequenzen.

Numerous birth-control studies, epidemiological studies, and observational studies have investigated mental health and health care in childhood, adolescence and early adulthood, including prevalence, age at onset, adversities, illness persistence, service use, treatment delay and course of illness. Moreover, the impact of the burden of illness, of deficits of present health care systems, and the efficacy and effectiveness of early intervention services on mental health were evaluated. According to these data, most mental disorders start during childhood, adolescence and early adulthood. Many children, adolescents and young adults are exposed to single or multiple adversities, which increase the risk for (early) manifestations of mental diseases as well as for their chronicity. Early-onset mental disorders often persist into adulthood. Service use by children, adolescents and young adults is low, even lower than for adult patients. Moreover, there is often a long delay between onset of illness and first adequate treatment with a variety of linked consequences for a poorer psychosocial prognosis. This leads to a large burden of illness with respect to disability and costs. As a consequence several countries have implemented so-called "early intervention services" at the interface of child and adolescent and adult psychiatry. Emerging studies show that these health-care structures are effective and efficient. Part 1 of the present review summarises the current state of mental health in childhood, adolescence and early adulthood, including prevalence, age at onset, adversities, illness persistence, service use, and treatment delay with consequences.

[Mental health of children, adolescents and young adults--part 2: burden of illness, deficits of the German health care system and efficacy and effectiveness of early intervention services]. / Die psychische Gesundheit von Kindern, Jugendlichen und jungen Erwachsenen--Teil 2: Krankheitslast, Defizite des deutschen Versorgungssystems, Effektivität und Effizienz von "Early Intervention Services"

Numerous birth-control studies, epidemiological studies, and observational studies investigated mental health and health care in childhood, adolescence and early adulthood, including prevalence, age at onset, adversities, illness persistence, service use, treatment delay and course of illness. Moreover, the impact of the burden of illness, of deficits of present health care systems, and the efficacy and effectiveness of early intervention services on mental health were evaluated. According to these data, most mental disorders start during childhood, adolescence and early adulthood. Many children, adolescents and young adults are exposed to single or multiple adversities, which increase the risk for (early) manifestations of mental diseases as well as for their chronicity. Early-onset mental disorders often persist into adulthood. Service use of children, adolescents and young adults is low, even lower than in adult patients. Moreover, there is often a long delay between onset of illness and first adequate treatment with a variety of linked consequences for poorer psychosocial prognosis. This leads to a large burden of illness with respect to disability and costs. As a consequence several countries have implemented so-called "early intervention services" at the border of child and adolescent and adult psychiatry. Emerging studies show that these health care structures are effective and efficient. Part 2 of the present review focuses on illness burden including disability and costs, deficits of the present health care system in Germany, and efficacy and efficiency of early intervention services.

Malassezia-derived indoles activate the aryl hydrocarbon receptor and inhibit Toll-like receptor-induced maturation in monocyte-derived dendritic cells.

BACKGROUND: The aryl hydrocarbon receptor (AhR) is a nuclear receptor and transcriptional regulator with pleiotropic effects. The production of potent AhR ligands by Malassezia yeasts, such as indirubin, indolo[3,2-b]carbazole (ICZ), tryptanthrin and malassezin, has been associated with the pathogenesis of seborrhoeic dermatitis and pityriasis versicolor. Antigen-presenting cells in the skin can encounter microbes in the presence of these bioactive metabolites that could potentially modulate their function. OBJECTIVES: To study the effects of the aforementioned naturally occurring ligands on AhR activation and Toll-like receptor (TLR)-induced maturation in human monocyte-derived dendritic cells (moDCs). METHODS: These indoles were screened for AhR activation capacity in moDCs employing CYP1A1 and CYP1B1 induction as read out and for their effects on the function of moDCs after TLR-ligand stimulation. RESULTS: Indirubin and ICZ were the most potent AhR ligands and were selected for subsequent experiments. Concurrent exposure of moDCs to indirubin or ICZ together with TLR agonists significantly augmented the AhR-mediated CYP1A1 and CYP1B1 gene expression. Additionally, mature DCs that were subsequently stimulated with AhR ligands showed increased AhR target gene expression. Moreover, these ligands limited TLR-induced phenotypic maturation (CD80, CD83, CD86, MHC II upregulation) of moDCs, reduced secretion of the inflammatory cytokines interleukin (IL)-6 and IL-12, and decreased their ability to induce alloreactive T-lymphocyte proliferation. CONCLUSIONS: These results demonstrate that AhR agonists of yeast origin are able to inhibit moDC responses to TLR ligands and that moDCs can adapt through increased transcription of metabolizing enzymes such as CYP1A1 and CYP1B1.

[Prison health is public health! Problems in adapting and implementing health services for prisoners in Germany. A review]. / Prison Health is Public Health! Angleichungs- und Umsetzungsprobleme in der gesundheitlichen Versorgung Gefangener im deutschen Justizvollzug Ein Ubersichtsbeitrag.

On the basis of international standards, health care in German prisons has been oriented along the principle of equivalence (equity of health care delivery for inmates compared with the health care delivery in the community). Against this background, selected health problems demonstrate not only isolated problems in adaptation and implementation of health care delivery, but also structural problems resulting from the parallel system of prison health care, which is separated from the general German health care insurance system. This review serves as a basis to present suggestions to rethink and reorganize prison-based health care services.

Light-induced anomalous Hall effect in graphene.

Many non-equilibrium phenomena have been discovered or predicted in optically-driven quantum solids1. Examples include light-induced superconductivity2,3 and Floquet-engineered topological phases4-8. These are short lived effects that should lead to measurable changes in electrical transport, which can be characterized using an ultrafast device architecture based on photoconductive switches9. Here, we report the observation of a light-induced anomalous Hall effect in monolayer graphene driven by a femtosecond pulse of circularly polarized light. The dependence of the effect on a gate potential used to tune the Fermi level reveals multiple features that reflect a Floquet-engineered topological band structure4,5, similar to the band structure originally proposed by Haldane10. This includes an approximately 60 meV wide conductance plateau centered at the Dirac point, where a gap of equal magnitude is predicted to open. We find that when the Fermi level lies within this plateau, the estimated anomalous Hall conductance saturates around 1.8±0.4 e2/h.

Increased number of Clostridium difficile infections and prevalence of Clostridium difficile PCR ribotype 001 in southern Germany.

In recent years, Clostridium difficile infection (CDI) has emerged as an increasing problem, both in in- and outpatients. In a rural region of southern Germany, the annual number of C. difficile toxin (Tcd)-positive patients has increased from 95 to 796 in the period from 2000 to 2007. Simultaneously, the proportion of positive tests among all Tcd examinations has risen from 7.0% to 12.8%, indicating that the higher number of affected patients was not solely due to an increase in the number of assays. Elevated numbers of CDI have recently been associated with outbreaks of the ribotype 027 strain, particularly in North America. This strain has also been isolated in Europe, including in Germany. Ribotyping and PCR testing for binary toxin genes of C. difficile strains isolated from in- and outpatients demonstrate a predominance (59%) of C. difficile ribotype 001, which exhibits antibiotic resistance to erythromycin, ciprofloxacin, and moxifloxacin, but lacks binary toxin genes. In summary, in our region of Germany, the number of patients affected by CDI has increased, probably due to spread of C. difficile ribotype 001.

Discrimination between epidemic and non-epidemic glycopeptide-resistant E. faecium in a post-outbreak situation.

Vancomycin-resistant enterococci (VRE) have been isolated in increasing numbers. Hospital-adapted VRE exhibit relatively high pathogenicity by expressing factors like enterococcal surface protein (Esp), which facilitates epidemic spread. By contrast, 'community-acquired' VRE show low pathogenicity and non-epidemic features. In 2004 and 2005 an extended outbreak of VRE occurred at a university hospital in Southwestern Germany and an infection control programme was implemented to confine the outbreak. Pulsed-field gel electrophoresis (PFGE), esp PCR, multiple-locus variable number of tandem repeat analysis (MLVA), purK1 typing and multiple-locus sequence typing (MLST) were performed on representative VRE isolates. Twenty-six non-epidemic and two epidemic VRE types (MLST203, MLST280) were identified by PFGE. Seven of the non-outbreak VRE types were esp gene negative, whereas 19 non-outbreak and both epidemic VRE types were esp positive. Eight MLVA types were identified. MLVA type 1 included five PFGE types and MLVA type 159 included 16 PFGE types. Currently there is no efficient method available to identify non-epidemic VRE and avoid unnecessary isolation of patients. More than 50% non-epidemic clones were esp positive; nevertheless, esp PCR appears to be the most promising approach to identify non-epidemic VRE.

[Balloon-assisted percutaneous vertebroplasty in patients with osteoporotic vertebral body compression fractures--first results]. / Ballonassistierte perkutane Vertebroplastie bei Patienten mit osteoporotischen Wirbelkörperkompressionsfrakturen -- erste Ergebnisse.

PURPOSE: To determine the feasibility, efficacy and safety of balloon-assisted percutaneous vertebroplasty (BA-VP) in patients with osteoporotic vertebral compression fractures (VCFs). MATERIALS AND METHODS: In 47 patients (29 women, 18 men; mean age: 70 years and 4 months) with severe VCFs, 66 BA-VPs were performed via a unipedicular access. After initial puncture (under combined fluoroscopy and CT guidance) of the vertebral body (VB), the needle was retraced by 1.5 cm, and a 12-mm Fogarty balloon catheter was introduced and inflated using 2-4 ml diluted contrast media (CM). After the subsequent removal of the catheter and repositioning of the needle, vertebroplasty was performed. RESULTS: The mean volume of PMMA injected was 4.4 ml (2.5-7.2 ml). Pain reduction (measured by the Visual Analogue Scale) was achieved in 95 % of the patients, dropping from on average 8.0 pre-intervention to 2.2 after a mean follow-up of 8 months. A reduction of the pain relieving medication was achieved in 68 % of the cases and patient activity improved markedly. No severe or clinically relevant complications were observed. Cement leakage occurred by filling of epidural and paravertebral veins in 9.1 and 6.1 % of the cases, respectively. Leakage into the paravertebral soft tissues was seen in 3.0 % of the patients and to the adjacent disc space in 10.6 % of the cases. CONCLUSION: Vertebroplasty and kyphoplasty are currently used to treat osteoporotic VCFs but show either a comparatively high leakage rate or are rather complex and expensive. Balloon-assisted vertebroplasty seems to combine advantages from both methods and is effective, safe and comparatively inexpensive.

Isolation and characterization of the rat gene encoding ornithine aminotransferase.

Herein we describe the isolation and characterization of the rat gene encoding ornithine aminotransferase (rOAT). Six unique genomic clones were characterized and assigned to two nonoverlapping contigs representing approx. 33 kb of the rat genome. The 5' contig contains the rOAT promoter, exons 1 and 3, and a portion of exon 4; an exon corresponding to exon 2 of the human OAT gene (hOAT) was not identified. The rOAT promoter contains several putative regulatory elements in positions similar to hOAT. The 3' contig contains exons 7 through 11 in their entirety. Data presented and discussed herein suggest that approx. 3.0 kb of uncloned genomic DNA, containing the remainder of exon 4 and all of exons 5 and 6, separate the two contigs. Together, these data suggest that rOAT extends over approx. 20 kb and is organized into at least 10 exons, thereby closely resembling hOAT in size and exon/intron organization. Isolation of rOAT provides an important tool for examining the molecular mechanisms through which estrogen and thyroid hormone regulate transcription of this gene in a cell-type specific manner.

Selective antagonists reveal different functions of M cholinoceptor subtypes in humans.

Effects of atropine and of the subtype selective mAChR antagonists pirenzepine (PZ) and AF-DX 116 were studied in humans. Dose- or time-response curves were established for heart rate and salivary flow. Plasma samples were drawn in parallel with the effect measurements and analysed for drug concentrations. Subtype-selective radioreceptor assays of the samples served to estimate the respective receptor occupancy in vivo. It is shown that low doses of PZ (M1-selective blockade) cause cholinomimetic effects indicated by bradycardia and increase in salivary flow. After high doses of PZ or atropine, tachycardia and inhibition of salivary flow are observed in parallel with occupancy of both the M2 and M3 subtypes. AF-DX 116 induces a tachycardia together with an increased salivary flow in agreement with its selectivity profile (M2 greater than M1 greater than M3). The diagnostic and therapeutic applications of M1- or M2-selective blockade by low dose PZ or AF-DX 116 respectively are discussed.

Inhibition of the calcium- and voltage-dependent big conductance potassium channel ameliorates cisplatin-induced apoptosis in spiral ligament fibrocytes of the cochlea.

The role of calcium- and voltage-dependent big conductance potassium channels in regulating apoptosis was investigated in cultured type I spiral ligament fibrocytes. Incubation of type I spiral ligament fibrocytes derived from gerbil cochlea with cisplatin induced dose- and time-dependent apoptosis as demonstrated by annexin V conjugated to fluorescein isothiocyanate/prodidium iodide assays. The average voltage activation threshold of whole cell current was sharply shifted to -40 mV in the cisplatin-treated cells as compared with a value of 40 mV in control cells. The average whole-cell current of cisplatin-treated cells induced by a depolarization voltage step from -80 to -10 mV was increased significantly to 1.2+/-0.4 nA as compared with 0.08+/-0.1 nA in control cells. Coincubation with tetraethylammonium and cisplatin retained the whole cell current in the normal range (0.12+/-0.2 nA). The increment of cisplatin-induced whole-cell current was inhibited (97+/-5%) by a specific calcium- and voltage-dependent big conductance potassium channel blocker iberiotoxin. Consistent with this, co-incubation with tetraethylammonium significantly attenuated cisplatin-induced apoptosis in type I spiral ligament fibrocytes by more than 50%. We conclude that the activation of BK channels is an early event associated with cisplatin-induced apoptosis in type I spiral ligament fibrocytes. These findings also point to the calcium- and voltage-dependent big conductance potassium channels as a potential pharmacological target for manipulating cisplatin ototoxicity.

Ouabain induces apoptotic cell death in type I spiral ganglion neurons, but not type II neurons.

Application of ouabain to the intact round-window (RW) membrane of the gerbil cochlea induces apoptosis in most spiral ganglion neurons (SGNs), leaving a few neurons intact (Schmiedt et al. 2002). Here, physiological measures and immunostaining were used to examine the process of SGN degeneration at 3, 6, 12, and 24 h, 4 days, and 1 and 5 months after ouabain treatment. The few remaining neurons surviving up to 5 months after ouabain treatment were immunoreactive for peripherin, a type II neuron marker. Peripherin-positive cell counts indicate that about 7% of the SGNs in the gerbil cochlea are type II neurons, and these neurons survive intact after ouabain treatment. Ouabain exposure had little effect on the outer hair cell and lateral wall systems, even after a 5 month loss of auditory-nerve function. The cellular locations of cytochrome c, poly (ADP-ribose) polymerase (PARP), and activated caspase 3 were examined in control and ouabain-treated cochleas. A redistribution of cytochrome c in peripherin-negative (type I) neurons was observed at 3 h after ouabain exposure. Degraded PARP and activated caspase 3 were also detected in peripherin-negative SGNs at 6 and 24 h after treatment, respectively. These results suggest that the redistribution of cytochrome c is an early event during apoptosis in type I SGNs and that activation of PARP and caspase 3 are associated with apoptosis in these cells. Calcineurin and NF-kappaB are two important signaling pathways that may modulate cell survival in the central nervous system. Here, we found that calcineurin and NF-kappaB selectively labeled type II neurons. It is speculated that the high levels of calcineurin and NF-kappaB in type II SGNs, as compared with type I SGNs, may play protective roles in enhancing the survival of type II neurons exposed to ouabain.

Ventricular function and Na+,K(+)-ATPase activity and distribution with chronic supraventricular tachycardia.

STUDY OBJECTIVE: The molecular and cellular mechanisms responsible for the dilated cardiomyopathy associated with chronic supraventricular tachycardia are not well understood. The purpose of this study was to examine Na+,K(+)-ATPase activity and distribution in a pacing induced model of dilated cardiomyopathy. DESIGN: Left ventricular function and Na+,K(+)-ATPase activity and distribution were examined in two groups of pigs: (1) atrially paced for 3 weeks (supraventricular tachycardia, 240 beats.min-1); (2) sham operated controls. SUBJECTS: 10 Yorkshire male swine (23-25 kg) were randomly assigned to the control group or the supraventricular tachycardia group. MEASUREMENTS AND MAIN RESULTS: Left ventricular function was examined using simultaneous pressure echocardiography. Na+,K(+)-ATPase activity was determined in tissue homogenates by measuring the rate of p-nitrophenol-phosphate (pNPP) hydrolysis. Changes in content and distribution of Na+,K(+)-ATPase were examined immuno-histochemically in tissue sections. Left ventricular fractional shortening decreased significantly with supraventricular tachycardia as compared to controls, at 15 (SEM 3)% v 31(3)%, respectively p less than 0.05. Supraventricular tachycardia resulted in a significant increase in end diastolic dimension [5.0(0.3) cm v 3.5(0.2) cm, respectively p less than 0.05] and pressure [22(4)mm Hg v 6(2)mm Hg, respectively p less than 0.05]. Maximal Na+,K(+)-ATPase activity (microgram pNPP.mg-1 protein.h-1) was significantly lower with supraventricular tachycardia than in controls, at 0.45(0.12) v 0.64(0.06), respectively p less than 0.05. In the presence of 7 microM digitalis, Na+,K(+)-ATPase activity was inhibited by 68% in control and by 45% in supraventricular tachycardia homogenates (p less than 0.05). In control sections all left ventricular myocytes showed a uniform immunostaining pattern along the sarcolemma for Na+,K(+)-ATPase, whereas a focal loss of staining was observed in myocytes from the supraventricular tachycardia group. CONCLUSIONS: The congestive cardiomyopathy produced by supraventricular tachycardia was associated with a reduction in sarcolemmal Na+,K(+)-ATPase activity and changes in enzyme distribution. The findings also suggest a reduction in digitalis sensitivity with chronic supraventricular tachycardia. These alterations in Na+,K(+)-ATPase activity may be one potential mechanism responsible for the depressed left ventricular function associated with chronic supraventricular tachycardia.

The effect of pinealectomy on seasonal changes in prolactin secretion in the white-tailed deer (Odocoileus virginianus borealis).

Surgery was performed on four buck and four doe 9-month-old white-tailed deer in March of 1978. Pinealectomy was performed on two deer of each sex, and the remaining animals received sham operations. At monthly intervals over the following year, baseline and TRH-stimulated (200 microgram/deer, iv bolus) serum PRL was measured over a 3-h period by RIA. Baseline PRL levels in sham-operated animals followed a circannual pattern, with peak levels occurring in June (74-237 ng/ml for does; 34-193 ng/ml for bucks) and lowest levels occurring in midwinter (0.41-0.44 ng/ml for does; 0.10-0.13 ng/ml for bucks). Pituitary responsivity to TRH followed the same patterns as that seen for basal PRL levels in sham-operated deer, with the highest peak serum PRL responses in June (198-568 ng/ml for does; 190-395 ng/ml for bucks) and the lowest peaks seen in midwinter (0.27-0.80 ng/ml for dose; 0.29-2.62 ng/ml for bucks). Pinealectomy appeared to abolish the circannual basal serum PRL rhythms in bucks, while this rhythm was maintained in does. Basal PRL levels in pinealectomized bucks ranged from 0.36-10.5 ng/ml, and basal levels in pinealectomized does ranged from 0.10-29.4 ng/ml. The greatest peak PRL response to TRH in pinealectomized deer was seen in August (41.2-93.4 ng/ml for does; 32.0-40.5 ng/ml for bucks), while the lowest peak response occurred in January (0.33-11.0 ng/ml for does; 0.50-17.0 ng/ml for bucks). Both sexes retained a degree of seasonality in their pituitary responsiveness to TRH, but the magnitude of the response in pinealectomized deer was greatly diminished in the summer months and increased in the winter months. Our results show that pinealectomy alters the naturally occurring photoperiod-linked seasonal profile of serum PRL in white-tailed deer and the associated pituitary responsiveness to TRH.

Cell loss and shrinkage in the nucleus basalis Meynert complex in Alzheimer's disease.

Marked neuron loss in the nucleus basalis of Meynert complex (NBMC) in Alzheimer's disease has repeatedly been reported in the literature. However, most of these studies quantitated only magnocellular, hyperchromatic (putative cholinergic) neurons of just a small part of the NBMC, and counts were expressed as numerical density. Applying a 3-dimensional-sampling design throughout the entire rostrocaudal extent of the NBMC and sampling neurons regardless of their size and staining characteristics, an overall neuron loss of only 15.5% was demonstrated for the whole NBMC. Neuron loss varied from 0% rostrally in the NBMC up to 36% in the most caudal part of the nucleus basalis of Meynert. Moreover, a significant increase in the number of small-sized neurons and a significant decrease in the number of large, putative cholinergic neurons could be detected, suggesting that apart from neuron loss neuron shrinkage appears to be another characteristic neuropathological feature of this degenerating cholinergic NBMC system. Preservation of these magnocellular cholinergic neurons in shrunken form renders it likely that cholinergic dysfunction, characteristic of Alzheimer's disease, may be responsive to neurotrophic influences.