Investigation of a scabies outbreak in a kindergarten in Constance, Germany.

In industrialized countries, scabies occurs sporadically or in the form of protracted epidemics, typically in nursing homes for elderly people. Outbreaks of scabies in a kindergarten are very rare. The main goal of our study was to investigate an outbreak of scabies in a kindergarten and to identify risk factors for the infestation with the ectoparasitosis. We investigated an outbreak of scabies in a kindergarten in the City of Constance, southern Germany, with a particular pedagogical concept. Risk factors indicating a transmission of Sarcoptes mites through body contact or via fomites were assessed using questionnaires and by following the daily routine in the kindergarten. A total of 16 cases were identified. The attack rate was significantly higher in nursery teachers (risk ratio 42.1) compared to children (risk ratio 10.5). In all cases, scabies had developed rather recently, with minimal clinical manifestations. In nursery teachers, the probability of scabies was 4.4 times higher in those teachers who hugged children regularly. Children who preferably played with their own soft toys had a lower probability of developing scabies [risk ratio 0.14, 95 % confidence interval (CI) 0.05-0.42; p = 0.04]. It seems conceivable that the particular pedagogical concept of the kindergarten favored the spread of Sarcoptes mites. We were unable to show whether transmission had preferably occurred through body contact or via fomites.

Morphine stimulates platelet-derived growth factor receptor-ß signalling in mesangial cells in vitro and transgenic sickle mouse kidney in vivo.

BACKGROUND: Pain and renal dysfunction occur in sickle cell disease. Morphine used to treat pain also co-activates platelet-derived growth factor receptor-ß (PDGFR-ß), which can adversely affect renal disease. We examined the influence of morphine in mesangial cells in vitro and in mouse kidneys in vivo. METHODS: > Mouse mesangial cells treated with 1 µM morphine in vitro or kidneys of transgenic homozygous or hemizygous sickle or control mice (n=3 for each), treated with morphine (0.75, 1.4, 2.14, 2.8, 3.6, and 4.3 mg kg(-1) day(-1) in two divided doses during the first, second, third, fourth, fifth, and sixth weeks, respectively), were used. Western blotting, bromylated deoxy uridine incorporation-based cell proliferation assay, reverse transcriptase-polymerase chain reaction, immunofluorescent microscopy, and blood/urine chemistry were used to analyse signalling, cell proliferation, opioid receptor (OP) expression, and renal function. RESULTS: Morphine stimulated phosphorylation of PDGFR-ß and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) to the same extent as induced by platelet-derived growth factor-BB (PDGF-BB) and promoted a two-fold increase in mesangial cell proliferation. The PDGFR-ß inhibitor, AG1296, OP antagonists, and silencing of µ- and κ-OP abrogated morphine-induced MAPK/ERK phosphorylation and proliferation by ~100%. Morphine treatment of transgenic mice resulted in phosphorylation of PDGFR-ß, MAPK/ERK, and signal transducer and activator of transcription 3 (Stat3) in the kidneys. Morphine inhibited micturition and blood urea nitrogen (BUN) clearance and increased BUN and urinary protein in sickle mice. CONCLUSION: Morphine stimulates mitogenic signalling leading to mesangial cell proliferation and promotes renal dysfunction in sickle mice.

Health-Related Quality of Life Following Concussion in Collegiate Student-Athletes With and Without Concussion History.

The purpose of this study was to compare global and specific health-related quality of life (HRQOL) throughout concussion recovery between those with and without concussion history. Student-athletes diagnosed with concussion completed global (Short Form-12v2; SF-12) and specific (Hospital Anxiety and Depression Scale: HADS) HRQOL assessments at baseline, 24-48 h, asymptomatic, return-to-play, and 6-months post-injury. Baseline scores were compared to post-injury time points for SF-12 subscores (physical and mental; PCS-12, MCS-12) and HADS subscores (depression and anxiety; HADS-D, HADS-A). We conducted a 2 × 5 mixed model ANOVA for group (with and without concussion history) and time (four post-injury assessments compared to baseline). We did not observe interaction or main effects for group, except those with concussion history had worse HADS-D subscores than those without concussion history. PCS-12 subscores were worse at 24-48 h, asymptomatic, and return-to-play compared to baseline, but returned to baseline 6-months post-injury. MCS-12 subscores did not differ at any time points. HADS-D subscores worsened 24-48 h post-injury, but improved for additional assessments compared to baseline. HADS-A improved post-injury compared to baseline at asymptomatic, return-to-play, and 6-month assessments, but was similar to baseline 24-48 h post-injury. HRQOL physical aspects slightly worsened post-injury and restored to baseline after returning to play.

Diminution of bone mass in childhood diabetes.

Photon absorption measurements of forearm bone density in 196 insulin-dependent patients, age 6--26 years, were compared with findings in 124 controls. Expected density, gm. Ca/cm.2 bone width (M/W), was calculated from regressions of M/W on ulnar length for white and black male and female controls. There were no significant correlations between M/W differences from expected and serum Ca, Mg, P, or alkaline phosphatase levels, estimated physical activity level, insulin dosage, or the presence of joint contracture. White females averaged 8.2 per cent (+/- 1 S.E.M.) loss of M/W, as against white male average loss of 4.7 per cent +/- 1 and black female loss of 2 per cent +/- 2 (p less than 0.001); the black male population was too small for separate analysis. M/W loss greater than 10 per cent was seen in 29 per cent of white males, 19 per cent of blacks, and 48 per cent of white females (p less than 0.02). When the groups were further divided into those with duration of diabetes less than or equal to five years and those with duration greater than five years, significant reduction in M/W average loss over time was seen with white females (10.6 per cent +/- 1.2 to 3.7 per cent+/- 1.5, p less than 0.0001). Expression of this defect in bone mineralization is controlled by race and sex acting independently of each other.

Synthesis of a series of 4-benzyloxyaniline analogues as neuronal N-type calcium channel blockers with improved anticonvulsant and analgesic properties.

In this article, the rationale for the design, synthesis, and biological evaluation of a series of N-type voltage-sensitive calcium channel (VSCC) blockers is described. N-Type VSCC blockers, such as ziconotide, have shown utility in several models of stroke and pain. Modification of the previously reported lead, 1a, led to several 4-(4-benzyloxylphenyl)piperidine structures with potent in vitro and in vivo activities. In this series, the most interesting compound, (S)-2-amino-1-{4-[(4-benzyloxy-phenyl)-(3-methyl-but-2-enyl)-amino]-p iperidin-1-yl}-4-methyl-pentan-1-one (11), blocked N-type calcium channels (IC(50) = 0.67 microM in the IMR32 assay) and was efficacious in the audiogenic DBA/2 seizure mouse model (ED(50) = 6 mg/kg, iv) as well as the antiwrithing model (ED(50) = 6 mg/kg, iv). Whole-cell voltage-clamp electrophysiology experiments demonstrated that compound 11 blocked N-type Ca(2+) channels and Na(+) channels in superior cervical ganglion neurons at similar concentrations. Compound 11, which showed superior in vivo efficacy, stands out as an interesting lead for further development of neurotherapeutic agents in this series.

Intercellular adhesion molecule-1 expression in endothelial cells is activated by cytomegalovirus immediate early proteins.

BACKGROUND: Human cytomegalovirus (HCMV) infection is associated with allograft vasculopathy and rejection. One potential mechanism is vascular injury from immunologically mediated processes. HCMV infection has been shown to increase the constitutive expression of intercellular adhesion molecule-1 (ICAM-1). The objective of this study was to determine the molecular basis of HCMV enhanced ICAM-1 gene expression in endothelial cells using human umbilical vein endothelial cells (HUVECs) as a model. METHODS: HUVECS were infected with HCMV virus and the level of ICAM-1 mRNA determined over time. HUVECS were then transiently transfected with plasmid constructs containing ICAM-1 and HCMV immediate early (IE) gene sequences and the effect of IE proteins on ICAM-1 promoter expression determined. Antibodies to cytokines known to be affected by HCMV IE proteins or to modulate ICAM-1 expression were added to determine if cytokines were mediating ICAM-1 expression. RESULTS: Infection of HUVECs with HCMV resulted in a rapid rise in ICAM-1 mRNA levels, suggesting that the viral IE proteins were involved in gene activation. The HCMV IE1 and IE2 proteins synergistically activated both transfected and endogenous ICAM-1 gene expression. The addition of antibodies to interleukin-1, tumor necrosis factor-a, transforming growth factor-beta, or interleukin-6 had no effect on the IE protein-mediated increase in ICAM-1 expression. Deletion analysis of the ICAM-1 gene promoter revealed that a minimum of 370 base pairs of 5' flanking sequences was required for maximal transactivation by IE proteins; mutation analysis showed that an NFkappaB site at base pairs -187 to -178 was not required for promoter activation. CONCLUSIONS: These results demonstrate that HCMV regulates the heterologous ICAM-1 gene promoter in endothelial cells not via cellular cytokine production, but rather by a direct effect of IE proteins, and supports a model in which HCMV IE gene products interact with ICAM-1 promoter elements to increase gene expression.

Effect of temperature on synaptic function after reduced oxygen and glucose in hippocampal slices.

We performed experiments in vitro to observe electrophysiological events that may relate to the protective effect of decreased temperature during cerebral ischemia in vivo. Extracellular field potentials were recorded from area CA1 of rat hippocampal slices with reduced oxygen and 2.0 mM D-glucose, producing irreversible changes within c. 10 min (more slowly than with complete deprivation of oxygen and glucose but more rapidly than with hypoxia alone). At 36 degrees C, synaptic potentials rapidly disappeared, followed by a d.c. negative shift similar to spreading depression. Elevated oxygen and glucose were reapplied within 5 min of each negative shift (duration of hypoxia ranged from 15 to 21 min). Application of normal medium for up to 45 min after negative shifts did not allow synaptic potentials to recover. At 33 degrees C negative shifts from reduced oxygen were delayed and excitatory postsynaptic potentials recovered in one experiment. At 31 degrees C negative shifts were usually absent and synaptic potentials always recovered, even with > 50 min of reduced oxygen and glucose. At both 33 degrees C and 31 degrees C, excitatory postsynaptic potential amplitude oscillated one or more times, whether or not a negative shift occurred. Our results show that negative shifts and irreversible loss of synaptic activity from hypoxia in vitro are delayed or prevented by decreased temperature.

Effects of ion channel blockade on the distribution of Na, K, Ca and other elements in oxygen-glucose deprived CA1 hippocampal neurons.

The pathophysiology of brain ischemia and reperfusion injury involves perturbation of intraneuronal ion homeostasis. To identify relevant routes of ion flux, rat hippocampal slices were perfused with selective voltage- or ligand-gated ion channel blockers during experimental oxygen-glucose deprivation and subsequent reperfusion. Electron probe X-ray microanalysis was used to quantitate water content and concentrations of Na, K, Ca and other elements in morphological compartments (cytoplasm, mitochondria and nuclei) of individual CA1 pyramidal cell bodies. Blockade of voltage-gated channel-mediated Na+ entry with tetrodotoxin (1 microM) or lidocaine (200 microM) significantly reduced excess intraneuronal Na and Ca accumulation in all compartments and decreased respective K loss. Voltage-gated Ca2+ channel blockade with the L-type antagonist nitrendipine (10 microM) decreased Ca entry and modestly preserved CA1 cell elemental composition and water content. However, a lower concentration of nitrendipine (1 microM) and the N-, P-subtype Ca2+ channel blocker omega-conotoxin MVIIC (3 microM) were ineffective. Glutamate receptor blockade with the N-methyl-D-aspartate (NMDA) receptor-subtype antagonist 3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid (CPP; 100 microM) or the alpha-amino-3-hydroxy-5-methyl-4-isoazole propionic acid (AMPA) receptor subtype blocker 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM/100 microM glycine) completely prevented Na and Ca accumulation and partially preserved intraneuronal K concentrations. Finally, the increase in neuronal water content normally associated with oxygen-glucose deprivation/reperfusion was prevented by Na+ channel or glutamate receptor blockade. Results of the present study demonstrate that antagonism of either postsynaptic NMDA or AMPA glutaminergic receptor subtypes provided nearly complete protection against ion and water deregulation in nerve cells subjected to experimental ischemia followed by reperfusion. This suggests activation of ionophoric glutaminergic receptors is involved in loss of neuronal osmoregulation and ion homeostasis. Na+ channel blockade also effectively diminished neuronal ion and water derangement during oxygen-glucose deprivation and reperfusion. Prevention of elevated Nai+ levels is likely to provide neuroprotection by decreasing presynaptic glutamate release and by improving cellular osmoregulation, adenosine triphosphate utilization and Ca2+ clearance. Thus, we suggest that voltage-gated tetrodotoxin-sensitive Na+ channels and glutamate-gated ionotropic NMDA or AMPA receptors are important routes of ion flux during nerve cell injury induced by oxygen-glucose deprivation/reperfusion.

Acute epiglottitis in children-treatment with nasotracheal intubation: report of 14 consecutive cases.

Fourteen consecutive cases of acute epiglottitis were treated by nasotracheal intubation during a ten-month period. The duration of intubation averaged 47.2 hours. No mortality or morbidity occurred. Mean hospitalization was 4.6 days. This study demonstrates the ease of maintaining an assured airway by nasotracheal intubation in cases of acute epiglottitis.

Myeloperoxidase deficiency with extensive candidal osteomyelitis of the base of the skull.

A 6-year-old girl had a 7-month history of headaches and painful torticollis. A CT scan of the mastoids showed extensive bone destruction of the base of the skull and C-1. Biopsies of the retropharyngeal area and of the anterior aspect of C-1 were performed: histopathologic findings were suggestive of mycotic infection and cultures were positive for Candida albicans. The child was treated successfully with amphotericin B. The immunologic evaluation demonstrated the absence of myeloperoxidase in the neutrophils.

The microbiology of serous and mucoid otitis media.

One hundred forty-four serous and mucoid effusions were cultured for aerobic bacteria, Mycoplasma pneumoniae, and virus. Thirty percent of all effusions yielded an unequivocally positive culture for aerobic bacteria. Although serous effusions were culture positive as often as mucoid effusions, Haemophilus influenzae was isolated predominantly from serous effusions and Staphylococcus epidermidis predominantly from mucoid samples. Only one of 73 effusions yielded a viral isolate (Herpesvirus hominis). None of 33 effusions yielded M pneumoniae, and only one of 17 effusions yielded an anaerobe (Propionibacterium). These findings suggest that aerobic bacteria may play a role in the pathogensis of serous and mucoid otitis media.

Hippocampal slices: glutamate overflow and cellular damage from ischemia are reduced by sodium-channel blockade.

We evaluated concentrations of excitatory amino acids released from slices into the superfusing solution and also evaluated extracellular field potential recordings and histological appearance of slice tissues to evaluate several sodium-channel modulating drugs as potential treatments for ischemia. The selective sodium-channel blocker tetrodotoxin (TTX, 1 microM) reduced glutamate release from deprivation of oxygen and D-glucose, while calcium-channel blockade was ineffective. Thus, during ischemia, we propose that glutamate may be released from the free cytosolic pool ('metabolic' glutamate) rather than by exocytosis. TTX (100-500 nM) and voltage-dependent sodium-channel blockers (phenytoin, 20-100 microM; lidocaine, 2-200 microM) each prevented damage to slices without blocking action potentials. The reduction of cellular depolarization and sodium loading during ischemia may explain the neuroprotective action of several sodium-channel modulating drugs in our in vitro studies and also in animal models.

Damage from oxygen and glucose deprivation in hippocampal slices is prevented by tetrodotoxin, lidocaine and phenytoin without blockade of action potentials.

In vitro ischemia (IVI) was simulated with rat hippocampal slices in medium lacking D-glucose, equilibrated with 95% nitrogen, 5% carbon dioxide. Within 5-8 min, synaptic potentials disappeared and a DC negative shift (5-15 mV) occurred. Prolonged application of 95% oxygen and D-glucose 12 min later did not allow synaptic potentials to recover. Slices pretreated with sodium channel blocking drugs allowed synaptic potentials to recover after IVI. Tetrodotoxin (TTX, 100-600 nM), the anticonvulsant phenytoin (5.0 to 100 microM) and the local anesthetic lidocaine (2.0 to 200 microM) each delayed or prevented negative DC shifts from IVI. Histological examination showed that drug treatments also prevented CA1 pyramidal cell damage from IVI. Neuroprotection occurred without blocking synaptic potentials or presynaptic fiber volleys, suggesting relevance for treatment of brain ischemia.

Treatment with conotoxin, an 'N-type' calcium channel blocker, in neuronal hypoxic-ischemic injury.

Therapeutic efficacy of calcium channel blockers in stroke remains controversial, but previously used agents bind almost exclusively to L-type calcium channels. The newly-discovered N-type calcium channel is specific to neurons, and therapy involving blockade of this site has not been previously attempted. We assessed the neuroprotective effect of omega-conotoxin GVIA (CgTx), a blocker of N-type calcium channels, using both in vitro hypoxic injury to rat cortical neurons and an in vivo model of reversible spinal cord ischemia in the rabbit. In cell cultures, CgTx inhibited hypoxia-induced 45Ca accumulation and neuronal injury minimally, compared to the NMDA antagonist ketamine. In vivo, the duration of spinal cord ischemia which produced permanent paraplegia in 50% of control animals (ET50) was 24.0 +/- 2.6 min. Animals treated 2 h prior to ischemia with 0.5 nmol CgTx in the subarachnoid space had an ET50 of 26.9 +/- 1.8 min (P = 0.36). Animals treated 24 h prior to ischemia (all had persistent systemic tremor) had a ET50 of 28.9 +/- 1.8 min (P = 0.13). We conclude that pharmacologic modulation of the N-type calcium channel does not provide a significant protective effect against neuronal hypoxic-ischemic injury.

A model of subretinal neovascularization in the pigmented rat.

We produced krypton laser photocoagulation lesions of mild to moderate whiteness in the posterior retinas of one eye of 23 pigmented rats, and identical appearing argon laser burns in the fellow eyes. We observed foci of subretinal neovascularization, histopathologically markedly similar to that which occurs in several human retinal diseases, in the krypton laser treated eyes of 6 of the 14 rats that were followed for one to three months after photocoagulation. No such lesions were observed in the argon laser treated fellow eyes, nor in krypton or argon laser treated eyes examined earlier than one month after photocoagulation. The photocoagulation damaged only the choriocapillaris, the retinal pigment epithelium (RPE), and the photoreceptor layer. In the acute lesions, we did not observe ruptures in Bruch's membrane. The neovascularization was surrounded by multiple layers of RPE cells, a histopathologic finding that has also been reported in some human eyes with subretinal neovascularization in age-related macular degeneration. These observations suggest that the RPE cells may be modifying the proliferative behavior of adjacent choroidal capillaries. This model differs from previous models of subretinal neovascularization in primates, and may be useful for additional studies of this important pathological process.

Retinovitreal neovascularization in the Royal College of Surgeons rat.

Retinovitreal blood vessels, which we have previously reported in the dystrophic retinas of approximately 20% of older (greater than 15 months of age) spontaneously hypertensive (SHR) rats, also occur in about 20% of retinal dystrophic Royal College of Surgeons (RCS) rats greater than 1 year of age. We have demonstrated previously that these vessels, in the SHR rat, have the anatomic characteristics of retinovitreal neovascularization as it has been described in vasoproliferative retinopathies in humans (1). We now provide strong evidence that the endothelial cells and pericytes of the retinovitreal vessels that occur in RCS rats are proliferating, since they demonstrate by autoradiography significantly increased nuclear labeling with [3H]-thymidine over intra-retinal or choroidal vessels, or the abnormal vessels that grow within the retinal pigment epithelium in these dystrophic retinas. One important difference between the neovascularization that occurs in these rats and that which is observed in various human retinal vascular diseases is the frequent association of the new vessels in dystrophic rat retinas with surrounding cords of proliferating retinal pigment epithelium. The retinovitreal vessels in these strains of dystrophic rats represent a new animal model that may be useful for studying the fundamental processes underlying new blood vessel growth in the retina.