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Acute acalculous cholecystitis. An increasing entity.

Acute acalculous cholecystitis was observed to increase in frequency between 1950 and 1979, an increase that was statistically significant. The greatest part of this increase occurred between 1965 and 1979. Acute acalculous cholecystitis was also found to be associated with a higher mortality rate, more than twice that of acute calculous cholecystitis. Acute acalculous cholecystitis occurred in a variety of clinical settings including bacterial sepsis, severe trauma including surgical trauma and burns, multiple transfusions, and severe debilitation. The lesion in the gallbladder consists of intense injury of blood vessels in the muscularis and serosa similar to those induced experimentally by in vivo activation of factor XII dependent pathways. Possibly because of the intensity of vascular injury, acute acalculous cholecystitis with minimal clinical manifestations may rapidly progress to gangrene with perforation. Undelayed surgical treatment, which has become more widely accepted over the past 50 years, is essential. It may have also contributed to the increased recognition of this clinical entity.

Adult↗

Transesophageal echocardiographic guidance of transseptal left heart catheterization during radiofrequency ablation of left-sided accessory pathways in humans.

UNLABELLED: Radiofrequency ablation (RFA) of left-sided accessory pathways can be achieved using catheters introduced by a retrograde or transseptal approach. Transesophageal echocardiography (TEE) has previously been demonstrated to be safe and efficacious in guiding transseptal puncture in patients during mitral valvuloplasty (MV). This study was undertaken to assess the feasibility, safety, and clinical utility of TEE during transseptal puncture and RFA of left-sided accessory pathways. METHODS: TEE was performed during transseptal puncture in 30 patients (41 +/- 12 years, 19 females), 15 patients during attempted RFA of a left-sided accessory pathway and 15 patients during attempted balloon MV. RESULTS: There was no difference in age, sex distribution, or procedural complications when MV patients were compared to RFA patients. At baseline, left atrial dimension was increased and congestive heart failure was more common when MV patients were compared to RFA patients (P < 0.05) Adequate baseline two-dimensional and Doppler TEE images were obtained in all patients. One patient sustained mild esophageal bleeding during the TEE. Positioning of the transseptal catheter in the fossa ovalis was facilitated and confirmed by TEE in 29 of 30 cases. One case of cardiac perforation occurred and was associated with inadequate TEE localization of the fossa ovalis. Thrombus was detected on the transseptal catheter by TEE in two cases prior to systemic heparinization. In both cases, thrombus was removed without embolic event. CONCLUSIONS: TEE safely guides transseptal puncture in patients undergoing RFA of left-sided accessory pathways. TEE markers of the fossa ovalis facilitate puncture and may reduce the risk of cardiac perforation particularly in patients with a normal size left atrium. TEE may be especially valuable for identifying thrombus during transseptal puncture.

Adolescent↗

Immunohistochemical demonstration of plasticity in GABA neurons of the adult rat dentate gyrus.

The distribution of GABA fibers within the dentate gyrus was immunohistochemically examined following lesions of the entorhinal cortex in the adult rat. A major change in the pattern of the GAD immunoreactive fibers within the molecular layer, characterized by a marked increase in the density of fibers in the outer molecular layer, was observed. This change in the lamination of the dentate GABA fibers following entorhinal lesions appeared very similar to the changes which occur in acetylcholinesterase staining following entorhinal denervation of the dentate. These results provide morphological support for the sprouting of GABA fibers in the dentate gyrus in response to perforant path destruction.

Acetylcholinesterase↗

Characteristics of CA1 activation through the hippocampal trisynaptic pathway in the unanaesthetized rat.

The hippocampal CA1 field is activated by the entorhinal cortex mainly through the hippocampal excitatory trisynaptic circuit. Field responses of the CA1 region were evoked by ipsilateral CA3 or perforant path volley (mono- or trisynaptic activation, respectively) in paralyzed, locally anaesthetized rats and studied as a function of the stimulus patterns presented. The relationship of these responses with the concomitant EEG was also explored. Results showed that mono- and especially trisynaptically evoked responses were progressively enhanced by increasing the stimulus frequency from 0.1 to 1.0 Hz. At specific intensities the trisynaptically evoked population spike (PS) was present only with a rather fixed frequency of stimulation (approximately 0.5 Hz). PS was produced in 100% of the responses using 0.7 Hz, indicating the existence of a threshold-like level for this stimulus parameter. The frequency of presented paired pulses differentially affected pair-pulse facilitation of mono- and trisynaptically evoked excitatory postsynaptic potentials (EPSP): higher frequency decreased the former and increased the latter. All evoked responses studied (i.e. EPSP and PS) showed steep increments and decrements in amplitude, clearly developing several clusters. Moreover, the amplitude distribution of trisynaptic PS often varied spontaneously from maximal to negligible values, showing an all-or-none distribution. Clustering was interpreted as evidence of the existence in the hippocampus of functional neuronal aggregates. All-or-none distribution of trisynaptic PS was found to be associated with the EEG pattern, PS amplitude being maximal during irregular EEG activity and minimal during theta rhythm. Present results suggest that (1) the entorhinal cortex may exert modulatory actions on CA1 by a mechanism widely based on the frequency of the input; (2) information transfer from the entorhinal cortex to other brain areas throughout the hippocampus is biased by hippocampal EEG; and (3) electronic coupling may be functionally predominant in the hippocampus.

Animals↗

Novel recognition site for L-quisqualate sensitizes neurons to depolarization by L-2-amino-4-phosphonobutanoate (L-AP4).

Brief exposure of rat hippocampal slices to L-quisqualate sensitizes pyramidal neurons to depolarization by L-2-amino-4-phosphonobutanoate (L-AP4). We report here experiments designed to clarify the duration, pharmacology, mechanism, and pathway specificity of this 'QUIS-effect'. The quisqualate-induced sensitization to L-AP4 decreases only 3-fold over a 4 h period. No compound besides quisqualate has been found to induce the QUIS-effect, including quisqualate analogues, potent excitatory amino acid agonists, L-glutamate, L-aspartate, and compounds known to stimulate second messenger systems in hippocampal slices. Of 43 compounds assayed here, only 5 are able to block the induction of the QUIS-effect. Although these blockers are also potent ligands at a chloride-dependent glutamate uptake site, the marked difference in rank ordering of compounds for QUIS-effect blockade and uptake site potency suggests that the QUIS-effect is not induced through this uptake site. The QUIS-effect can be induced in the CA1 region, the medial perforant path, and the lateral olfactory tract of the rat, and in the guinea pig CA1. It cannot be induced in the L-AP4-sensitive rat lateral perforant path (LPP), suggesting that the receptors for L-AP4 in the LPP may be distinct from those that are sensitized by quisqualate in the other pathways.

Action Potentials↗

Gradual angioplasty and stent implantation to treat complete superior vena cava occlusion after Mustard procedure.

A 16-year-old male was admitted with complete occlusion of the superior vena cava pathway 14 years after Mustard procedure for transposition of the great arteries. From a left subclavian vein approach, the atretic vein segment was perforated using a straight guidewire, and was followed by sequential balloon dilation. Implantation of a 30 mm Palmaz-stent through a femoral vein approach resulted in a widely patent channel of the vena cava superior into the systemic venous atrium.

Adolescent↗

Functional innervation of cultured hippocampal neurones by cholinergic afferents from co-cultured septal explants.

The rat hippocampus receives a strong cholinergic innervation from the medial septum; information about the development and function of this pathway could help to elucidate the mechanisms of memory functions. Previous electrophysiological studies have shown that septal stimulation in vivo facilitates commissural and perforant path inputs and that stimulation of intrahippocampal cholinergic fibres in vitro produces a slow depolarization of rat hippocampal CA3 pyramidal neurones and increases their excitability. We describe here a different approach to the investigation of this system, by co-culturing slices of young rat hippocampus and septum, then recording the effects of septal nucleus stimulation on single voltage-clamped hippocampal CA3 pyramidal neurones. Under these conditions acetylcholinesterase-staining (presumed cholinergic) fibres grow out from the septum into the hippocampus. Single septal stimuli produce a short-latency non-cholinergic fast excitatory postsynaptic current, whereas trains of stimuli produce a slow inward current augmented by neostigmine and suppressed by atropine; hence this has a cholinergic origin. Our experiments provide both the first demonstration that functional synapses can be established between explanted cholinergic and cholinoceptive neuronal systems from the mammalian brain in organotypic culture and the first description of cholinergic slow excitatory postsynaptic currents in the mammalian central nervous system.

Animals↗

[Penetrating keratoplasty in free form using the excimer laser--first application in a patient].

BACKGROUND: Conventional mechanical trephination techniques limit penetrating keratoplasty to the use of circular transplants. Certain special indications, however, would profit from the application of non-circular transplants. We describe our first case, in which we applied a newly developed technique for congruent trephination of donor and recipient cornea in free form with the excimer laser in a patient. CASE REPORT AND METHOD: Excimer laser trephination was applied on the cornea of a 74-year old female patient who presented with a perforated peripheral corneal ulcer. The affected corneal tissue was replaced by an individually adapted transplant. Trephination was achieved by a 1.0 mm laser beam, which was guided along a predetermined pathway. RESULTS: Excimer laser trephination achieved completely congruent dimensions of donor button and recipient bed in a kidney shape. Laser trephination was carried out nearly down to Descemet's membrane. The cut in the remaining deep tissue was completed with a diamond knife. The postoperative course was uneventful. Follow-up at four months postoperatively showed a well healed clear transplant, which did not reach the optical axis of the cornea. CONCLUSIONS: This first application of the newly developed trephination technique represents a valuable addition in corneal transplant surgery in special indications. In the case demonstrated here, an eye with perforated corneal ulcer could be visually rehabilitated rapidly with only a minimal volume of transplanted tissue.

Aged↗

Ethanol affects hypothalamic neurons projecting to the hippocampus and inhibits dentate granule cell LTP.

In previous studies we demonstrated that ethanol inhibition of hippocampal granule cell long-term potentiation (LTP) is mediated by angiotensin II (AII), and the inhibition can be blocked by losartan, a specific AII receptor antagonist. The purpose of the present study was to demonstrate that this low-dose ethanol inhibition of dentate granule cell LTP induction is mediated by lateral hypothalamic (LH) afferents that project to the granule cells. In urethane anesthetized rats, we compared the effects of ethanol infusion, 6.0 microliter/30 min, by means of an open-ended push-pull type cannula, in both the LH and the dentate gyrus, on dentate granule cell LTP. Results demonstrate a dose-dependent inhibition of LTP induction when the LH is perfused that can be blocked by losartan, 10 mg/kg i.p.. Four doses of ethanol were used: 5, 10, 20, and 30 mM. There was no effect when the dentate gyrus was infused with 30 mM ethanol and normal granule cell LTP was observed. Also, these results demonstrate for the first time a low-dose ethanol effect on a physiological function, LTP in a specific neural pathway, directly related to the anterograde amnesia produced by ethanol on short-term memory. Therefore, these data support our hypothesis that ethanol inhibition of LTP induction at the medial perforant path-granule cell synapse can be attributed to a presynaptic release of AII and cannot be explained in terms of a direct postsynaptic effect on the granule cells.

Angiotensin II↗

Radiofrequency catheter ablation of atrioventricular accessory pathways: experience in 179 patients.

Radiofrequency catheter ablation was used to treat 179 patients aged 5 to 79 (37 +/- 17) years. Six patients had multiple accessory pathways. The total number of accessory pathways was 188, 47 conducting only retrogradely; among them, 8 had retrograde decremental properties. The location of the accessory pathways was: 81 at the left lateral position; 13 left posterior; 15 left posteroseptal; 24 posteroseptal; 16 midseptal; 16 right posteroseptal; 17 anteroseptal and 6 right lateral. All patients were symptomatic and six had congenital heart disease. Initial success was achieved in 159 patients (88.8%). Ten out the 20 patients in whom ablation failed underwent a second attempt and success was obtained in all but 3 patients. Final success was accomplished in 166 patients (92.7%). There were 14 recurrences (7.8%) all successfully ablated during a second procedure. The mean procedure duration time was 80 +/- 60 minutes, the mean radiation exposure time was 31 +/- 26 minutes and the mean number of radiofrequency applications was 9 +/- 10. Three patients developed complete atrioventricular block during the procedure requiring permanent pacing, one patient had a perforation of a previously unknown congenital aneurysm of the aorta solved by surgery and one patient had a transient amaurosis after the procedure attributed to microembolization. Radiofrequency ablation of accessory pathways is a safe and effective treatment.

Adolescent↗

B7/CD28 costimulation is critical in susceptibility to Pseudomonas aeruginosa corneal infection: a comparative study using monoclonal antibody blockade and CD28-deficient mice.

Evidence suggests that Pseudomonas aeruginosa stromal keratitis and corneal perforation (susceptibility) is a CD4(+) T cell-regulated inflammatory response following experimental P. aeruginosa infection. This study examined the role of Langerhans cells (LC) and the B7/CD28 costimulatory pathway in P. aeruginosa-infected cornea and the contribution of costimulatory signaling by this pathway to disease pathology. After bacterial challenge, the number of LC infiltrating the central cornea was compared in susceptible C57BL/6 (B6) vs resistant (cornea heals) BALB/c mice. LC were more numerous at 1 and 6 days postinfection (p.i.), but were similar at 4 days p.i., in susceptible vs resistant mice. Mature, B7 positive-stained LC in the cornea and pseudomonas Ag-associated LC in draining cervical lymph nodes also were increased significantly p.i. in susceptible mice. To test the relevance of these data, B6 mice were treated systemically and subconjunctivally with neutralizing B7 (B7-1/B7-2) mAbs. Treatment decreased corneal disease severity and reduced significantly the number of B7-positive cells as well as the recruitment and activation of CD4(+) T cells in the cornea. IFN-gamma mRNA levels also were decreased significantly in the cornea and in draining cervical lymph nodes of mAb-treated mice. When CD28(-/-) animals were tested, they exhibited a less severe disease response (no corneal perforation) than wild-type B6 mice and had a significantly lower delayed-type hypersensitivity response to heat-killed pseudomonas Ag. These results support a critical role for B7/CD28 costimulation in susceptibility to P. aeruginosa ocular infection.

Animals↗

Bidirectional modulation of exocytosis by angiotensin II involves multiple G-protein-regulated transduction pathways in chromaffin cells.

Angiotensin II (AngII) receptors couple to a multitude of different types of G-proteins resulting in activation of numerous signaling pathways. In this study we examined the consequences of this promiscuous G-protein coupling on secretion. Chromaffin cells were voltage-clamped at -80 mV in perforated-patch configuration, and Ca(2+)-dependent exocytosis was evoked with brief voltage steps to +20 mV. Vesicle fusion was monitored by changes in membrane capacitance (DeltaC(m)), and released catecholamine was detected with single-cell amperometry. Ca(2+) signaling was studied by recording voltage-dependent Ca(2+) currents (I(Ca)) and by measuring intracellular Ca(2+) ([Ca(2+)](i)) with fura-2 AM. AngII inhibited I(Ca) (IC(50) = 0.3 nm) in a voltage-dependent, pertussis toxin (PTX)-sensitive manner consistent with G(i/o)-protein coupling to Ca(2+) channels. DeltaC(m) was modulated bi-directionally; subnanomolar AngII inhibited depolarization-evoked exocytosis, whereas higher concentrations, in spite of I(Ca) inhibition, potentiated DeltaC(m) fivefold (EC(50) = 3.4 nm). Potentiation of exocytosis by AngII involved activation of phospholipase C (PLC) and Ca(2+) mobilization from internal stores. PTX treatment did not affect AngII-dependent Ca(2+) mobilization or facilitation of exocytosis. However, protein kinase C (PKC) inhibitors decreased the facilitatory effects but not the inhibitory effects of AngII on stimulus-secretion coupling. The AngII type 1 receptor (AT1R) antagonist losartan blocked both inhibition and facilitation of secretion by AngII. The results of this study show that activation of multiple types of G-proteins and transduction pathways by a single neuromodulator acting through one receptor type can produce concentration-dependent, bi-directional regulation of exocytosis.

Adrenal Medulla↗

Endothelin-1 and photoreleased diacylglycerol increase L-type Ca2+ current by activation of protein kinase C in rat ventricular myocytes.

The amphotericin B-perforated whole-cell patch clamp technique was used to determine the modulation of L-type Ca2+ channels by protein kinase C (PKC)-mediated pathways in adult rat ventricular myocytes. Application of 10 nM endothelin-1 (ET-1) increased peak Ca2+ current (ICa) by 28.2 +/- 2.5 % (n = 13) and slowed current decay. These effects were prevented by the endothelin receptor antagonist PD145065 (10 microM) and by the PKC inhibitor chelerythrine (8 microM). To establish if direct activation of PKC mimicked the ET-1 effect, the active and inactive phorbol esters (phorbol-12-myristate-13-acetate and 4alpha-phorbol-12, 13-didecanoate) were tested. Both phorbol esters (100 nM) resulted in a small (approximately 10%) increase in ICa, suggesting PKC-independent effects. Bath application of dioctanoylglycerol (diC8), a diacylglycerol (DAG) analogue which is capable of directly activating PKC, caused a gradual decline in peak ICa (50.4 +/- 6.2 %, n = 5) and increased the rate of current decay. These effects were unaffected by the PKC inhibitor chelerythrine (8 microM). Intracellular photorelease of caged diC8 with 3 or 10 s exposure to UV light produced a concentration-dependent increase in peak ICa (20. 7 +/- 8.5 % (n = 8) for 3 s UV and 60.8 +/- 11.4 % (n = 13) for 10 s UV), which could be inhibited by chelerythrine. Our results demonstrate that both ET-1 and intracellularly photoreleased diC8 increase ICa by a PKC-mediated pathway, which is in direct contrast to the PKC-independent inhibition of ICa produced by bath-applied diC8. We conclude that specific cellular pools of DAG are crucially important in the regulation of ICa by PKC.

Alkaloids↗