The use of acupuncture in controlling the gag reflex in patients requiring an upper alginate impression: an audit.

BACKGROUND: A pronounced gag reflex (GR) can be a problem to both the acceptance and delivery of dental treatment. Despite a range of management strategies, some patients cannot accept even simple dental treatment. The aim of this study was to evaluate the use of acupuncture point CV-24 in controlling a profound gag reflex during dental treatment requiring an upper alginate impression. METHOD: Members of the British Dental Acupuncture Society were invited to take part in an audit of the role of acupuncture point CV-24 in controlling the gag reflex. They were issued with patient inclusion criteria, a standardised procedure instruction sheet and a recording form. All patients fulfilling the inclusion criteria had an upper dental alginate impression taken (or an attempt made at it) before acupuncture, and a second upper alginate impression taken immediately after acupuncture of point CV-24. The GR assessment was undertaken prior to insertion of the acupuncture needle using the Gagging Severity Index (GSI); and after the acupuncture and impression taking using the Gagging Prevention Index (GPI). Both the GSI and GPI were recorded at three stages of the dental impression taking procedure, ie, when the empty impression tray was tried in the mouth, when the loaded tray was inserted into the mouth, and on completion of the impression taking. RESULTS: Twenty-one dentists submitted 64 case reports of which 37 fulfilled the inclusion criteria. Prior to acupuncture all 37 patients (20 females and 17 males with a mean age of 46.8 years) were unable to accept the impression taking. After acupuncture of point CV-24, an improvement of between 51-55% (mean 53%) for the three stages of impression taking was noticed. Thirty patients (81%) were able to accept the impression taking, whereas seven (19%) remained unable to tolerate the procedure. Assessed by the GSI and GPI, there was a significant decrease in GR scores at all three stages of the impression taking procedure (median 3 vs 1; 4 vs 2; 4 vs 2; p < 0.0001). Thus before acupuncture, the patients had moderate to severe GR and after acupuncture the GR had reduced to a level which only complicated dental treatment slightly. CONCLUSION: Our results indicate that acupuncture of point CV-24 is an effective method of controlling severe GR during dental treatment including impression taking. However, the results of the current audit need to be tested in a randomised controlled study in order to substantiate the effectiveness of this method.

Size of neocortical neurons in control subjects and in Alzheimer's disease.

The aim of the present study was to estimate mean neuronal volume and absolute size distributions of the neocortical neurons in brains from controls and AD patients using stereological methods based on unbiased principles to determine whether changes in absolute cell size are part of the neuropathological pattern of Alzheimer's disease. The neocortex of 8 patients with Alzheimer's disease (AD), mean age 81.1 (68-94) y was compared with 9 nondemented controls, mean age 80.9 (65-101) y. The brains came from Johns Hopkins University Hospital (JHUH) in Baltimore, USA, the Netherlands Brain Bank (NBB), and from a large brain repository in Denmark. The rotator method was used to obtain an estimate of cell volumes providing absolute size distributions of the volume of both cell perikaryon and cell nuclei. The geometric mean volume of cell nuclei in neocortical neurons was 328 microm3 (interindividual CV = 0.15) in the Alzheimer group compared with 277 microm3 (interindividual CV = 0.17) in controls which was a statistically significant increase (P = 0.049). The perikaryal volume was 1117 microm3 in the Alzheimer group compared with 999 microm3 in controls which was a nonsignificant difference (P = 0.20). There was a highly significant correlation between the nuclear and perikaryal volumes in all individuals. The average slope of the regression lines was significantly higher in the Alzheimer patients than in the controls, illustrating that nuclear hypertrophy was more pronounced in the largest neurons.

[Non-specific symptoms and primary hyperparathyroidism]. / Ukarakteristiske symptomer og primaer hyperparatyreoidisme.

Primary hyperparathyroidism is diagnosed with increasing incidence. Many patients are misinterpreted as being asymptomatic, but they do indeed suffer from a broad variety of non-specific symptoms. Investigations show that patients with primary hyperparathyroidism may be lethargic, apathic, demented and depressed. Many suffer from bone and joint pain. Surgical treatment can be done with few complications and a high cure rate, resulting in reversal of symptoms. Since symptoms do not correlate with S-Ca++ or S-parathyroid hormone and since the symptoms can be attributed to many other causes, we need more research to find those patients, who will benefit from surgical treatment.

[Primary hyperparathyroidism with serum parathyroid hormone within the normal range]. / Primaer hyperparatyreoidisme med S-parathyreoideahormon i normalområdet.

Patients with primary hyperparathyroidism (PHPT) often suffer from muscle and bone pain, are often easily fatigued and may show depressive signs. We present a case of a 50 year-old man with PHPT with muscle pain and fatigue. After parathyroidectomy the symptoms resolved. Preoperatively he had a normal serum-parathyroid hormone (PTH) and an increased ionized serum-calcium. Postoperatively the PTH level increased, though still within the normal range.

Transport of protons and lactate in cultured human fetal retinal pigment epithelial cells.

Monolayer cultures of human fetal retinal pigment epithelial (RPE) cells were examined for ultrastructural characteristics and junctional integrity by means of electron microscopy. Intracellular pH (pHi) and cell volume changes were measured using the fluorescent dye BCECF. The EM studies indicate that the RPE cells preserve in vivo morphology before and after loading with BCECF. Monolayer cultures were placed in a perfusion chamber in which the solution facing the retinal cell membrane could be changed rapidly. Removal of Na+ or the addition of amiloride caused intracellular acidifications. pHi recovery from an NH4+-induced acid load was blocked by sodium removal or amiloride addition. These results suggest the presence of a Na+-H+ exchange mechanism in the retinal cell membrane. When Cl- was replaced isotonically by lactate or pyruvate the cells acidified. The intracellular acidifications were saturable, reversibly reduced with the inhibitor probenecid (2 mM), and the lactate-induced acidifications were reversibly inhibited by equimolar concentrations of pyruvate. These results indicate the presence of a H+-lactate cotransport mechanism in the retinal membrane. When Cl- was replaced by lactate the cells not only acidified, they also swelled. The data are compatible with water transport induced by the H+-lactate cotransporter.

Short-term results after aortic valve replacement with stentless xenografts in elderly patients.

OBJECTIVE: Our aim was to chart the short-term results of the first 75 of our patients who had undergone first-time aortic valve replacement (AVR) with stentless xenografts. DESIGN: Our study included a complete follow-up (mean/max. 1.5/3.7 years) of the first 75 patients (42 males, 33 females; mean age 74, range 61-84 years) who underwent a first AVR with stentless xenografts. RESULTS: Forty-three percent of patients were in functional class II and 57% in classes III-IV preoperatively. Coronary artery bypass grafting (CABG) was performed in 33 patients. Early mortality (< or = 30 days) was 6.7%, with no significant relation to CABG or age. Crude survival was 81% (95% confidence interval, CI: 71-91 %) at 3 years. Using a multivariate analysis, we identified a low left ventricular ejection fraction as a predictor of early and late mortality. Late survival (early mortality excluded) was comparable with the survival of a matched Danish background population. There were six embolic events (all cerebral: 3 minor, 1 major, 2 fatal), while two patients underwent redo-AVR because of either endocarditis (fatal) or aortic regurgitation caused by malaligned commissures. There were no other valve-related complications. Cumulative freedom was 89% (95% CI: 79-99%) for embolism and 86% (95% CI: 76-96 %) for all complications at 3 years. At the end of the study, 64% of the survivors were in functional class I, 34% were in class II and 2% in class III. CONCLUSIONS: Considering the age composition of our patients, and compared with international results, our early mortality rates were acceptable. The absence of late excess mortality compared with the background population and the functional status at end-of-study may indicate the potential haemodynamic advantages of stentless aortic valves, at least in the short term.

NOS activity in brain and endothelium: relation to hypercapnic rise of cerebral blood flow in rats.

We examined whether attenuation of the hypercapnic increase of cerebral blood flow (CBF) associated with nitric oxide synthase (NOS) inhibition is related to local neuronal or aortic endothelial NOS activity or local endothelial/neuronal NOS-dependent vasodilation. Halothane-anesthetized rats were ventilated, and CBF was measured by laser-Doppler flowmetry over the parietal and cerebellar cortex. Intravenous N omega-nitro-L-arginine (L-NNA; 30 mg/kg) inhibited brain and aortic NOS activity by 67-70%. Topical L-NNA (1 mM) inhibited brain NOS activity by 91-94%, whereas aortic NOS activity remained constant. In contrast, intravenous L-NNA attenuated the hypercapnic CBF rise much more efficiently than topical L-NNA. 7-Nitroindazole, another NOS inhibitor, attenuated endothelial and neuronal NOS activity equally well and inhibited the hypercapnic CBF increase as effectively as L-NNA. Topical L-NNA and 7-nitroindazole abolished local endothelial NOS-dependent vasodilation after 15 min, whereas hypercapnic CBF was only slightly reduced. L-NNA injected into the tissue abolished neuronal NOS-dependent vasodilation, whereas hypercapnic CBF was unchanged. The findings suggest that local NOS activity, whether neuronal or endothelial, is unimportant for the hypercapnic rise of CBF.

Quantitative estimation of the area of luminal and basolateral membranes of rat parotid acinar cells: some physiological applications.

Knowledge of luminal and basolateral acinar cell membrane areas of the secretory endpieces is a prerequisite for a detailed quantitative analysis of the ion transport involved in secretion of the primary saliva. In the present study, these areas were estimated in rat parotid acinar cells using standard stereological methods. A total of 480 micrographs--obtained by random sampling from eight glands from four rats--were analysed at a final magnification of 40000x. Expressed per unit cell volume, the area of the luminal acinar cell membrane was: 0.125 micron 2.micron-3 (SEM = 0.027 micron 2.micron-3, n = 4 animals) and the area of the basolateral membrane was: 1.54 microns 2.micron-3 (SEM = 0.085 micron 2.micron-3, n = 4 animals). These figures make it possible to perform a synthesis based upon different categories of experimental data, e.g. on ion fluxes, membrane potentials and single-channel conductances. Thus, we have estimated the density of open, low-conductance Cl- channels in the luminal membrane--which are not readily accessible for direct, patch-clamp analysis--to be approximately 18 channels per microns 2 in the stimulated state.

ATP-dependent closure and reactivation of inward rectifier K+ channels in endothelial cells.

This report presents the results of a patch-clamp study examining the role of intracellular ATP in the regulation of endothelial inward rectifier K+ channels. Administration of ATP to the cytosolic surface of inside-out patches reversibly activated the K+ channel within seconds. ATP (1 mM) increased the mean open probability by a factor of 3.5, primarily by increasing the number of openings. Administration of the nonhydrolyzable ATP analogue ATP-gamma-S failed to modulate channel activity. Inhibition of ATP synthesis by administration of cyanide plus iodoacetate resulted in channel closure within 1 to 6 minutes. In experiments in which ATP was coadministered with the metabolic blockers, the channel activity continued unchanged for up to 30 minutes, but when ATP was removed, the activity rapidly decayed. We propose that normal functioning of the inward rectifier K+ channel is ATP dependent. Phosphorylation of the channel molecule is probably essential for maintaining activity.

Fine structure of the blood-brain interface in the cuttlefish Sepia officinalis (Mollusca, Cephalopoda).

The blood-brain interface was studied in a cephalopod mollusc, the cuttlefish Sepia officinalis, by thin-section electron microscopy. Layers lining blood vessels in the optic and vertical lobes of the brain, counting from lumen outwards, include a layer of endothelial cells and associated basal lamina, a layer of pericytes and a second basal lamina, and perivascular glial cells. The distinction between endothelial cells and pericytes breaks down in small vessels. In the smallest microvessels, equivalent to capillaries, and in venous channels, and endothelial and pericyte layers are discontinuous, but a layer of glial cells is always interposed between blood and neural tissue, except where neurosecretory endings reach the second basal lamina. In microvessels in which cell membranes of the entire perivascular glial sheath could be followed, the glial layer was apparently 'seamless', not interrupted by an intercellular cleft, in ca 90% (27/30) of the profiles. Where a cleft did occur, it showed an elongated overlap zone between adjacent cells. The walls of venous channels are formed by lamellae of overlapping glial processes. In arterial vessels, the pericyte layer is thicker and more complete, with characteristic sinuous intercellular clefts. Arterioles are defined as vessels containing 'myofilaments' within pericytes, and arteries those in which the region of the second basal lamina is additionally expanded into a wide collagenous zone containing fibroblast-like cells and cell processes enclosing myofilaments. The 'glio-vascular channels' observed in Octopus brain are not a prominent feature of Sepia optic and vertical lobe. The organization of cell layers at the Sepia blood-brain interface suggests that it is designed to restrict permeability between blood and brain.

Electron-dense tracer evidence for a blood-brain barrier in the cuttlefish Sepia officinalis.

Electron-dense tracers were used to study the permeability of the blood-brain interface in a cephalopod mollusc, the cuttlefish Sepia officinalis. Gel filtration established that horseradish peroxidase is a suitable tracer for in vivo injection, but microperoxidase is not, being subject to binding by plasma proteins. Perfusion-fixed brain vertical and optic lobes showed no endogenous peroxidatic activity. Horseradish peroxidase was injected intravenously, and allowed to circulate for 10-35 min before tissue fixation by immersion or perfusion. Horseradish peroxidase reaction product was undetectable in the bulk of the brain parenchyma. In microvessels, venous vessels and at the brain surface, horseradish peroxidase penetrated the layers of endothelial and pericyte cells, being stopped by the layer of perivascular glia. In arterial vessels, tracer restriction occurred at the level of the pericytes. In the region of tracer blockade, a gradient of tracer could be traced in the intercellular cleft, from high at the luminal end to undetectable at the tissue end. The clefts of the restricting zone were generally wide (15-20 nm), with faint periodicities or linking structures spanning the cleft, and contained a fibrillar extracellular material. Perfusion of lanthanum chloride in saline for 15 min, followed by precipitation of lanthanum phosphate during fixation, resulted in lanthanum tracer distribution similar to that of horseradish peroxidase. Horseradish peroxidase was seen filling extracellular spaces within the neuropile when the blood-brain barrier was breached by a stab wound, indicating that the interstitium itself does not restrict tracer diffusion. It is concluded that Sepia has a blood-brain barrier tight to horseradish peroxidase and ionic lanthanum. The restricting junction is not a typical zonula occludens or septate junction, but appears to reduce tracer penetration by a filtering mechanism within the extracellular cleft. The barrier is formed by perivascular glial cell processes in the microvessels and venous vessels, but by pericytes in arterial vessels. This organization suggests that a glial blood-brain barrier may be the primitive condition, and a barrier associated with vascular elements (endothelium/pericyte) a later development.

A fibre matrix model for the restricting junction of the blood-brain barrier in a cephalopod mollusc: implications for capillary and epithelial permeability.

A model is proposed for the novel restricting junction forming the blood-brain barrier in a cephalopod mollusc, the cuttlefish Sepia officinalis. The model is based on electron-microscopic findings, from both thin-section and freeze-fracture material, the distribution of electron-dense tracers, and radioisotopic measurements of permeability using small non-electrolytes. Biochemical properties of Sepia plasma proteins are also considered. It is proposed that an effective blood-brain barrier is achieved by a combination of mechanisms. As much as 90% of the Sepia brain microvessel wall is covered by a 'seamless' glial sheath, without intercellular clefts, limiting the number of potential leakage sites. The remaining clefts follow a tortuous course increasing the diffusion path to the neuropile. Entry into the clefts is reduced by a restricting junctional region at the luminal end, characterized by delicate striations spanning the cleft, and forming an effective barrier to both horseradish peroxidase and ionic lanthanum. This is a novel junctional type, different from previously-described vertebrate and invertebrate occluding junctions. It is proposed that the junction acts as a fine-mesh molecular filter, with condensed extracellular material in the cleft, cross-linked and consolidated by bound plasma protein. Cephalopod haemocyanin or its subcomponents are considered likely candidates for the bound protein. The model predicts that blood-brain barrier permeability should be sensitive to the charge structure of the extracellular matrix and the presence of protein, and is analogous to the 'fibre matrix' model of vertebrate capillary permeability. The Sepia blood-brain barrier also highlights the different strategies available for constructing a restricting cell layer, and suggests a possible evolutionary pattern underlying the present range of junctional mechanisms in vertebrate and invertebrate epithelia.

Chloride-selective channels of large conductance in bovine aortic endothelial cells.

Single-channel currents of an anionic channel in the plasma membrane of cultured bovine aortic endothelial cells have been recorded with the patch-clamp technique. The channel is selective for chloride over cations, and has an average single channel conductance of 382 picosiemens in symmetric 140 millimoles of chloride. In addition to the main conductance state it shows well-defined subconductance states of about 50, 100, 150 and 200 picosiemens. The channel is very active at membrane potentials close to 0 mV, but steps to either positive or negative membrane potentials above +/- 20 millivolt lead to a rapid inactivation of the channel. Changes in the concentrations of free calcium or adenosine tri-phosphate on the cytosolic surface do not influence channel activity. The chloride channel rarely opens at resting membrane potential, but it may help repolarize endothelial cells following depolarizing stimuli.

The three-dimensional organization of smooth endoplasmic reticulum in capillary endothelia: its possible role in regulation of free cytosolic calcium.

A rise in cytosolic free Ca in capillary endothelia leads to increased permeability. It has been proposed that this Ca(2+)-regulated modulation of junctional permeability of vascular endothelia involves structural elements comparable to those involved in stimulus-contraction coupling in smooth muscle. To explore this analogy the three-dimensional organization of smooth-surfaced cisternae, vesicular membrane profiles, and tight junctions was examined in endothelia of diaphragm and heart capillaries of the rat. Three-dimensional reconstructions, based on consecutive sections of the capillaries, have demonstrated a population of small, irregular membrane profiles, occurring in individual thin sections of the endothelial cytoplasm. These profiles represent an elaborate system of smooth-surfaced cisternae, structurally similar to the sarcoplasmic reticulum (SR) of smooth muscle cells. Slender processes from the cisternae are often situated in parallel to the tight junctions at a distance of about 100 nm. The great majority of the characteristic circular membrane profiles represents caveolae and racemose invaginations of the endothelial plasma membrane, often in close relation to the cisternae. It is hypothesized that the endothelial cisternae and invaginations of the cell membrane are involved in regulation of free cytosolic calcium in the same way as the SR and caveolae in smooth muscle cells. The junction-related cisternal processes may play a role in the Ca(2+)-regulated modulation of junctional permeability.

Barrier membranes at the outer surface of the brain of an elasmobranch, Raja erinacea.

This report gives the results of the first electron-microscopic examination of the cell layers covering the outer brain surface and the inner surface of the cartilaginous skull in the skate, Raja erinacea. The perivascular glial blood-brain barrier--a characteristic of elasmobranchs--extends to the outer surface of the brain. This outer barrier layer is surrounded, in turn, by a subarachnoid compartment (depth: 30-40 microns), containing loose connective tissue and blood vessels; by an arachnoid-like epithelium (10-15 cell layers), impermeable to horseradish peroxidase; and, by perimeningeal fluid, a fluid with a slow turnover rate and a protein composition different from plasma. The inside of the skull, facing the perimeningeal fluid, is covered by a multilayered (10-15 layers) cuboidal epithelium, also impermeable to horseradish peroxidase. Closely apposed cells in the luminal layer of this epithelium have apical microvilli and numerous vesicular profiles, containing material of moderate electron density. These observations may explain, in terms of structure, the regulated protein content of perimeningeal fluid and the restricted exchange of solutes between brain and perimeningeal fluid in elasmobranchs.

Postsurgical change of mandibular position in patients following Le Fort I osteotomy.

Mandibular displacement during and following maxillary osteotomy was observed. Cephalometric data obtained from radiographs produced before, immediately after, and at a minimum of 6 months after were analyzed. The displacement of the maxilla and of the mandible during and after surgery was studied, and the predictive value of maxillary displacement on the changes occurring in the mandibular region was evaluated by a stepwise regression analysis. The results indicated that as the maxilla was displaced superiorly, the mandible also displaced anterosuperiorly without significant relapse. The rotation and the vertical displacement of the maxilla during the Le Fort I osteotomy accounted for two thirds of the total mandibular change. Vertical displacement of the maxilla and mandible were significantly correlated, indicating that mandibular displacement and rotation can be predicted from maxillary displacement.

Combined orthodontic-surgical treatment of alveolar clefts.

After more than four years of postoperative follow-up, 224 patients receiving secondary bone grafting of alveolar clefts were examined. Patients were classified into three groups according to age and eruption stage of the cleft side canine tooth at surgery. Each group was then subdivided according to the diagnoses cleft lip alveolar process only, unilateral cleft lip and palate, and bilateral cleft lip and palate. The treatment results were evaluated with respect to bone level in the cleft area, gingival and periodontal condition, orthodontic treatment result, growth of the jaws after surgery, and complications. The best results were achieved when the bone grafting was performed before eruption of the cleft side canine. In half of these patients orthodontic treatment could be finished with a closed dental arch without the need for prosthodontic treatment. The sagittal growth of the jaws was unaffected by the bone grafting, whereas the anterior height of the maxilla was reduced apparently without any clinical significance.

Functional implications of structural differences between consecutive segments of microvascular endothelium.

Structural and functional data which can be ascribed to consecutive segments of the microvascular bed are reviewed and tentatively correlated. Compared to the knowledge of endothelial cells in general, little is known about segmental variations of the microvascular endothelium. The gradient in microvascular permeability has been quantified by single capillary techniques. The results conform to structural data on endothelial tight junctions which indicate that pathways through the junctions occur with increasing frequency towards the venous end of the microvascular bed. A number of compounds mediate gap formation in venular endothelium presumably via endothelial surface-receptors. It has been demonstrated that receptors to histamine are preferentially located at the luminal surface of venular endothelium. Immunocytochemical localization of metabolic activities of microvascular endothelium in situ has started; thus it has been shown that specific antibodies to xanthine oxidase bind only to endothelium of true capillaries.