Remineralization of early caries by chewing sugar-free gum: a clinical study using quantitative light-induced fluorescence.

PURPOSE: To determine whether sugar-free gum can provide remineralization and caries control of active enamel caries lesions compared to baseline (before gum chewing) and to a no-gum group, following daily chewing for 12 weeks by school children; to determine whether chewing frequency can affect the extent of remineralization. METHOD: A pragmatic cluster-randomized controlled clinical trial with schools as the unit of randomization was employed. Three schools in Chengdu, PR China comprised the clusters. The study was approved by the Internal Review Board of Sichuan University. 177 school children, 8-13 years old, with at least one visible white-spot lesion were enrolled in the study. Each of the three clusters was randomly assigned to one of three groups: (1) no gum; (2) chew 2 pieces of sugar-free gum for 20 minutes, 3x per day; (3) chew 2 pieces of sugar-free gum for 12 minutes, 5x per day. White-spot lesions were examined by quantitative light-induced fluorescence (QLF) at baseline and after 4, 8, and 12 weeks of treatment. RESULTS: 155 subjects completed the study. Of them, the mean values of fluorescence loss at baseline were 9.52, 9.83 and 9.17 for no-gum group, 3x per day group and 5x per day group, respectively. For the area, the mean values at baseline were 2.52, 2.61 and 2.57 mm2 for no-gum group, 3x per day group and 5x per day group, respectively. For AQ, the mean values at baseline were -27.91, -28.29 and -29.67 for no-gum group, 3x per day group and 5x per day group, respectively. To adjust for differences in groups at baseline, ANCOVA was used. After 12-weeks, for all QLF metrics, the absolute values of 5x per day group were the lowest and the no gum group was the highest; the differences among three groups were statistically significant (P < 0.05). For AQ, which was accepted as the most useful metrics of QLF system, the adjusted mean values at 12 weeks were -26.35, -19.81 and -17.58 for no-gum group, 3x per day group and 5x per day group, respectively. There were significant differences between groups.

Hepatic influence on splenic synthesis and release of coagulation activities.

Isolated rabbit liver perfusates contain one or more puromycinsensitive factors that stimulate factor VIII and IX activities in splenic perfusates. Production of coagulation activity by a complementary process involving organ perfusates suggests existence of coagulation factor precursors. An analogy is made to appearance of high factor VIII activity after plasma transfusions in von Willebrand's disease.

Testing for food-specific antibodies in saliva and blood of food allergic and healthy dogs.

An elimination diet (ED) followed by re-challenge has been the reference standard to diagnose adverse food reactions (AFR) in dogs, but can be challenging to conduct. This study investigated the accuracy of a saliva-based test for food-specific IgA and IgM and an ELISA serum test for food-specific IgE. Three groups of dogs were tested. Group 1 (n=11) included dogs with previously diagnosed and controlled AFR; group 2 (n=15) comprised dogs with allergic dermatitis at the beginning of their ED; and group 3 (n=16) was composed of clinically healthy research dogs. Saliva samples were collected from all groups and blood samples from group 1 and group 3. The results of clinical re-challenges with individual food components were compared with the test results. Specificity, sensitivity, positive and negative predictive values and likelihood ratios were determined. Forty-one dogs completed the study; one dog was lost to follow up. There was a total of 163 re-challenges. Sensitivity, positive predictive value and likelihood ratio, specificity, negative predictive value and likelihood ratios were unsatisfactory for both tests in most instances, except for IgM testing in group 2, which had moderate specificity. There was no clear difference in the number of positive reactions between the allergic dogs and healthy dogs from a research population. Based on these results, the saliva test for food specific IgA and IgM and the ELISA serum test for food specific IgE were not reliable to diagnose adverse food reactions in dogs. Until more data are available, elimination diets remain the reference standard in the diagnosis of this disease.

Movement of the feline esophagus associated with respiration and peristalsis. An evaluation using tantalum markers.

The outer, lateral esophageal walls in the distal half of the esophagus in each of five cats were labeled with small tantalum wires. About 8 wk later, esophageal motion associated with respiration and peristalsis, induced by injecting barium boli (5 ml each) into the proximal esophagus, was recorded on cine and serial biplane roentgenograms while recording intraluminal esophageal pressures simultaneously by manometry. Esophageal motion was also evaluated without a manometric tube in place. The coordinates for each marker were digitized and a computer was used to plot marker position against time. During respiration, the markers passively made a shallow, 2-10 mm excursion on the longitudinal esophageal axis. This movement was synchronous with thoracic and diaphragmatic movement and changes in intraluminal esophageal pressure. Immediately after the onset of peristalsis, the markers made a pronounced oral movement of 10 mm or more above their mean respiratory position, as if to engulf the bolus. Markers in opposing esophageal walls approximated one another and commenced an aboral movement as the bolus tail, which was essentially co-incident with onset of the manometric pressure complex, passed the marker sites. The markers returned to their respective rest positions essentially coincident with passage of the pressure complex peak and then moved below their respective rest positions. The aboral excursion occurred predominantly after the bolus had emptied into the stomach. The magnitude and duration of oral excursion was significantly greater for the distal than for the more proximal markers; conversely, the magnitude and duration of aboral excursion was greater for the proximal than for the more distal markers. During the peristaltic sequence, the labeled portion of the esophagus shortened from 26 to 46% of its resting length. No evidence of esophageal torque was shown. These findings suggest that both the longitudinal and circular esophageal musculature play an active and important role during peristaltic transport of a bolus through the esophagus.

Mechanism of gastroesophageal reflux in recumbent asymptomatic human subjects.

We investigated the mechanism of gastroesophageal reflux (GER) in 10 health volunteer subjects. Continuous recordings of intraluminal esophageal pH and pressure were obtained on two consecutive nights from 6:00 p.m. to 6:30 a.m. in each subject. During each study, the subject remained recumbent, except to eat a standardized meal after 1 h of basal recording. A manometric assembly with seven recording lumens monitored: (a) lower esophageal sphincter (LES) pressure via a sleeve device 6.5 cm in length, (b) esophageal-body motor activity, (c) swallowing activity in the pharynx, and (d) gastric pressure. An electrode 5 cm above the LES recorded esophageal pH. Sleep was monitored by electroencephalogram. All subjects showed wide variations of basal LES pressure. GER was not related to low steady-state basal LES pressure, but rather occurred during transient 5-30 s episodes of inappropriate complete LES relaxation. The inappropriate LES relaxations were usually either spontaneous or immediately followed appropriate sphincter relaxation induced by swallowing. The majority of GER episodes occurred within the first 3 h after eating. During the night LES relaxation and GER occurred only during transient arousals from sleep or when the subjects were fully awake, but not during stable sleep. After GER the esophagus was generally cleared of refluxed acid by primary peristalsis and less frequently by secondary peristalsis. Nonperistaltic contractions were less effective than peristalsis for clearing acid from the esophagus. We conclude that in asymptomatic recumbent subjects GER is related to transient inappropriate LES relaxations rather than to low steady-state basal LES pressure and also, that primary perstalsis is the major mechanism that clears the esophagus of refluxed material.

Relationship of sphincter of Oddi spike bursts to gastrointestinal myoelectric activity in conscious opossums.

The oppossum sphincter of Oddi (SO) exhibits peristaltic spike bursts with accompanying contraction waves that originate proximally in the sphincter of Oddi and propagate toward the duodenum. In this study we recorded myoelectrical activity of the opossum SO and upper gastrointestinal tract in six conscious animals using chronically implanted electrodes. Biopolar electrodes were implanted in the gastric antrum, duodenum, SO segment, jejunum, and ileum. During fasting the frequency of SO spike bursts, scored as number per minute, showed a cyclic pattern consisting of four phases (A to D). Phase A had a low spike burst frequency of approximately 2/min that lasted approximately 20 min. In phase B, the spike burst frequency increased progressively during a 40-45 min interval culminating in a short interval of phase C activity characterized by a maximal spike burst frequency of approximately 5/min. During phase D, the spike bursts decreased over 15 min to merge with the low frequency of phase A and the cycle repeated. Cycle length of the interdigestive SO cycle, 87+/-11 SD min, was virtually identical with that of the interdigestive migrating myoelectric complex (MMC) of the upper gastrointestinal tract. The onset of phase C activity in the SO began 1-2 min before phase III of the MMC activity in the duodenum. Feeding abolished the cyclic pattern of spike burst activity in the SO as well as in the upper gastrointestinal tract. After feeding the SO spike bursts occurred at a frequency of 5-6/min for at least 3 h. We conclude that: (a) During fasting, the oppossum SO exhibits cyclic changes in its spike burst frequency; (b) Maximal spike burst frequency of the SO occurs virtually concurrent with passage of phase III MMC activity through the duodenum and; (c) Feeding abolishes the interdigestive cyclic spike burst pattern of the SO as well as that of the gastrointestinal tract.

Motor function of the opossum sphincter of Oddi.

We studied the opossum sphincter of Oddi (SO) because in this species the SO is approximately 3 cm in length and its extraduodenal location permits recording of motor activity with negligible interference from duodenal motor activity. The SO segment of 120 animals was evaluated by one or more of the following: (a) intraluminal manometry; (b) electromyography; (c) common bile duct (CBD) flow monitored by a drop counter; (d) cineradiography of intraductal contrast medium; and (e) histologic examination. SO pull-throughs using an infused catheter of 0.6-mm o.d. invariably showed a high pressure zone (HPZ) of 18 +/- 3 SE mm Hg in the terminal 4-5 mm of the SO segment. This HPZ had a narrow lumen, 0.5-0.7 mm in diam, and prominent circular muscle. The HPZ in the terminal SO had both active and passive components. HPZ with minimal amplitude and a paucity of underlying smooth muscle were present inconstantly at the junction of the SO segment with the CBD and pancreatic duct, respectively. The dominant feature of the SO segment was rhythmic peristaltic contractions that originated in the proximal SO and propagated toward the duodenum. These contractions occurred spontaneously at a rate of 2-8/min, ranged up to 200 mm Hg in magnitude, had a duration of approximately 5 s and were not abolished by tetrodotoxin. Concurrent myoelectric and manometric recordings showed that each phasic contraction was immediately preceded by an electrical spike burst. Simultaneous recordings of cineradiography, CBD inflow of contrast medium, SO manometry, and SO electromyography indicated that rhythmic peristaltic contractions stripped contrast medium from the SO into the duodenum. During SO systole, CBD emptying was transiently interrupted, whereas SO filling occurred during the diastolic interval between SO peristaltic contractions. SO distention increased the frequency of SO peristalsis. We conclude that (a) the dominant feature of the opossum SO is rhythmic peristaltic contractions that originate in the proximal SO and propagate toward the duodenum; (b) these forceful SO peristaltic contractions are myogenic in origin and serve as a peristaltic pump that actively empties the SO segment; (c) CBD outflow occurs passively during SO diastole, but is interrupted transiently during each SO peristaltic contraction; and (d) a short HPZ with active as well as passive components exists in the distal SO segment and acts as a variable resistor to SO outflow.

Von Willebrand factor (VIII R:Ag), fibronectin, and insulin-like growth factors I and II in diabetic retinopathy and nephropathy.

We have measured plasma von Willebrand factor (VWF) as the factor VIII-related antigen, plasma fibronectin, and two of the serum somatomedins, insulin-like growth factor I (IGF I) and IGF II, in 51 diabetic patients and 25 nondiabetic control subjects. VWF was significantly higher in the diabetic group than in the controls (173 +/- 9% SEM versus 101 +/- 9%, P less than 0.001), as has been reported by others. However, within the diabetic group there was no significant difference in VWF between those patients without retinopathy, those with background or proliferative retinopathy, or those with macular edema. There was also no difference in VWF between the diabetic subjects with and those without proteinuria. These results rule against a previously advanced hypothesis that the increase in VWF in patients with diabetes is secondary to microangiopathy. No significant difference was observed in fibronectin, IGF I, or IGF II between the diabetic and control groups, between the diabetic group without retinopathy and the retinopathic subgroups, and between the diabetic subjects with and without proteinuria. In the diabetic patients, there was no correlation between diabetic control as assessed by glycosylated hemoglobin and glycosylated serum protein, and the plasma levels of VWF, fibronectin, IGF I, or IGF II. The results of this study strongly suggest that neither plasma VWF, fibronectin, IGF I, nor IGF II plays an important primary role in the pathogenesis of diabetic microvascular disease, although one or more of these factors might play a permissive role.

Comparison of pseudoachalasia and achalasia.

Malignancies involving the gastric cardia or distal esophagus can result in a clinical syndrome termed pseudoachalasisa that mimics idiopathic achalasia. If not promptly recognized, pseudoachalasia can result in inappropriate pneumatic dilatation of the lower esophageal sphincter segment and delay appropriate treatment of the underlying malignancy. During the past 14 years, six patients with pseudoachalasia and 161 patients with primary idiopathic achalasia were encountered. Pseudoachalasia occurred mainly in the elderly and represented about 9 percent of these patients over 60 years of age with suspected achalasia. Five of the six pseudoachalasia cases were secondary to adenocarcinoma that originated in the gastric fundus, and one was caused by a squamous cell carcinoma of the distal esophagus. Conventional esophageal manometry did not discriminate achalasia from pseudoachalasia. On the other hand, esophagogastroscopy with biopsy resulted in a diagnosis of pseudoachalasia in five of these cases and in 24 of 32 cases reported previously. Ominous endoscopic findings are mucosal ulceration or nodularity, reduced compliance of the esophagogastric junction, or an inability to pass the endoscope into the stomach. Radiographic evaluation, particularly in conjunction with amyl nitrite inhalation, was also useful in discriminating pseudoachalasia from primary achalasia. It is concluded that pseudoachalasia generally mimics idiopathic achalasia imperfectly and can usually be diagnosed prior to surgery by fastidious endoscopic and radiographic examination.

Effects of reagent and instrument on prothrombin times, activated partial thromboplastin times and patient/control ratios.

Activated partial thromboplastin times accumulated from two proficiency testing surveys were analyzed to determine simultaneously the effects of the method and reagent used. Prothrombin time results were reevaluated concomitantly for comparison. A robust two-way analysis of variance was applied to determine the effect of method and reagent on APTT results. The effect of the reagent and method on the ratio of abnormal to normal plasma clotting times was determined. We found a substantial difference in ratios for the PT using different reagents on the same instrument. There was an even larger effect of reagents on APTT ratios. Our finding of substantial reagent effects for the PT and APTT clearly support the need for standardization. We found standardization to be feasible only for the PT, and only if applied in a form consistent with the inherent error structure of the data. For the APTT, the present methodology and plasma samples did not achieve consistent standardization.

A native whole blood assay for blood-materials interaction.

A convenient, accurate, and reproducible method was developed and characterized to test the effects of particulate solids and soluble agents on native whole blood. The effects of citrate anticoagulation and of variation in flow and column parameters were characterized by ancillary experiments. The study utilized a relatively homogeneous strain of large rabbits that had received intravenous [C14]-serotonin as a platelet radiolabel. The assay induced a 4 min contact time of either the test sample or saline control with freshly drawn arterial blood and was followed by a series of hemostatic measurements, both before and after passage of the blood through a standard 1 g glass bead column. Changes induced by soluble (ADP, ellagic acid, aspirin) and particulate (collagen) agents in the reactivity of this blood to the subsequent challenge of a large area of reactive surface revealed reproducible quantitative effects on platelets and clotting. Generally comparable results were obtained with native whole human blood when the glass bead surface was adjusted (2 g) for the species difference in coagulability and platelet reactivity.

Prothrombin time proficiency testing: a robust grading method.

A robust two-way analysis of variance technique was applied to determine simultaneously the effects of method and thromboplastin on prothrombin time. A new approach to outlier detection for two-way analysis of variance was used. Focusing on the underlying error structure improved the uniformity of the grading procedure in the hematology proficiency testing program of the New York State Department of Health. The logarithm-transformed scale produced constancy of error variance and resulted in uniformity of the acceptable spread of data. The common variance was lower than that obtained by previous methods and allowed for a narrower acceptable range of reported prothrombin times by reducing the inflated standard deviation, thus improving the efficiency of the grading procedure. For proficiency testing, no advantage was found in the use of either a common thromboplastin or freeze-dried, coumadinized patient plasmas rather than artificially depleted commercial plasmas, except for special purposes.

Non-thrombogenicity of clean glass revealed by native whole blood assay in bead columns.

The previously described native whole blood assay for materials in solution or suspension has been adapted to materials in a bead column configuration. These experiments showed that the glass itself accounts for little or none of the high blood-reactivity observed with conventional glass bead columns. Columns composed solely of soft glass that was "cleaned" by heat treatment (500-595 degrees C 18 hr, electric oven) were benign toward flowing native whole blood for all variables measured (platelet count and platelet-free plasma [C14]-serotonin content, platelet factor 3 and factor XII activities, and recalcification time) with the standard contact protocol. In addition, the effluent successfully maintained perfusion of the isolated kidney, a measure of the ability of platelets to support vascular integrity. Prolonged (30 min) normothermic contact with citrated whole blood increased the subsequent reactivity of initially clean glass toward whole blood albeit to a level much less than that of conventional glass bead columns.

Spontaneous atrial thrombosis in aged Syrian hamsters. II. Hemostasis.

Coagulation and fibrinolysis were studied in a colony of aged Syrian hamsters with spontaneous atrial thrombosis, and the results are consistent with concomitant consumption coagulopathy. In comparison to age- and sex-matched hamsters from the same colony, those with atrial thrombi had significantly prolonged prothrombin and partial thromboplastin times, reduced levels of factors II, VII, VIII and X activities and plasminogen; and concentrations of fibrinogen-fibrin split products in excess of 80 microgram/ml. Hematocrits of the thrombosed animals were significantly decreased, total plasma proteins were increased, leukocyte counts were within normal limits, and platelet counts were about half those of the controls. Thrombosed hamsters had significantly reduced plasma albumin content, increased alpha1-, beta-, and gamma-globulins, and reduced A/G ratios. Aged sick hamsters demonstrable thrombi also had reduced coagulation and fibrinolytic activities and platelet counts, but their fibrinogen levels were markedly elevated, and fibrinogen-fibrin split products were either absent or present in trace amounts. This suggests an earlier and/or less acute form of the thrombotic process.

Rectal balloons: complications, causes, and recommendations.

Nine previously unreported rectal injuries caused by barium-enema examinations have been reviewed. In each case, the injury occurred in conjunction with inflation of a rectal balloon. Analysis of the clinical material suggested that certain mechanical properties of balloon catheter tips might transfer mechanical stress to the rectal wall and contribute to the observed injuries. Careful manometric evaluation of in vivo rectal balloons suggest that significant anatomic differences in patients may be clinically important. Further experimental bench studies revealed undesirable mechanical properties in many commercially available rectal balloon catheters. These mechanical problems include low compliance, asymmetrical inflation, strong lateral and anterior displacement of a firm catheter tip into the restraining wall, and self-obstruction of the balloon deflation outlet by the inflated baloon. Many of these problems were clinically confirmed by careful in vivo observations and by evidence collected from the nine cases of rectal injury. A series of practical prophylactic procedures are recommended.

Requirements for accurate manometric recording of pharyngeal and esophageal peristaltic pressure waves.

The frequency characteristics and wave form of peristaltic pressure complexes occurring in the pharynx and esophagus of normal subjects were studied. For each of five subjects, five peristaltic waves were selected for analysis from the proximal and distal pharynx as well as the proximal, middle, and distal esophagus. Thus, 25 peristaltic waves were analyzed from each of the five regions studied, giving a total of 125 in all. After digitization of the peristaltic waves, pressure values were entered into a computer algorithm that performed a Fourier transformation to determine frequency content and wave slope. The computer analysis revealed that a frequency response flat to 5 Hz was adequate to record 98% of esophageal peristaltic waves with 98% accuracy. In contrast, recording accuracy up to 48 Hz was needed for high-fidelity recording in the pharynx. Rates of pressure change were substantially greater for pharyngeal peristaltic pressure complexes compared with esophageal peristaltic complexes. The results suggest that appropriately designed infused-catheter systems can readily meet the requirements for accurate recording of peristaltic pressure waves in the esophagus but not in the pharynx. Consequently, different instrumentation, such as an intraluminal strain gauge probe, is needed for accurate manometric recording of pharyngeal peristalsis.

Animal models for the evolution of thrombotic disease.

Naturally occurring hemorrhagic and thrombotic diseases of animals closely parallel their human counterparts. While such models may be particularly useful in studying the pathogenesis of human disease, it is usually more realistic to depend upon experimentally induced disease models. The species selected for use is therefore of major importance in providing meaningful extrapolation to humans, as are the experimental design and type of procedure (in vitro, ex vivo, in vivo). Regardless of the test system used when in vitro procedures are employed, these must be translated eventually to the in vivo situation. Information about the normal aging process of different species is important here and should influence selection of the species and test system. The ideal situation may not be feasible or pertain because of cost, availability, size, and investigator familiarity, or lack thereof, with the most suitable species or model.

Action of cholecystokinin-octapeptide on sphincter of Oddi basal pressure and phasic wave activity in humans.

The human sphincter of Oddi (SO) exhibits phasic wave activity over a 4 to 6 mm segment. Approximately 60% of these waves occur in an antegrade direction, 14% are retrograde, and 26% occur simultaneously. Because cholecystokinin-octapeptide (CCK-OP) stimulates the flow of bile into the duodenum, its effect on SO phasic wave contractions and contraction sequences was evaluated at ERCP manometry. An infused triple-lumen catheter of 1.7 mm outer diameter with side orifices spaced 2 mm apart was stationed in the SO segment so that all three orifices recorded phasic pressure waves. We studied 31 patients with normal ductal anatomy and normal SO pressures. In 21 of these patients CCK-OP (20 ng/kg) was given intravenously after a 2- to 3-minute baseline recording was obtained. Pressure recordings were continued for up to 10 minutes following CCK-OP administration. CCK-OP caused a significant inhibition in the frequency and amplitude of SO phasic waves as well as a significant decrease in basal SO pressure. Before CCK-OP most phasic contractions were antegrade, and after CCK-OP the sequence pattern remained unchanged. We conclude that CCK-OP reduces or transiently abolishes SO phasic contractions but that it does not change their temporal sequence. In addition, CCK-OP produces a decrease in basal SO pressure. These findings suggest that the action of CCK-OP in humans is to inhibit SO phasic activity and reduce SO basal pressure to allow increased flow of bile.

Coordination between respiration and swallowing: respiratory phase relationships and temporal integration.

The coordination of breathing and swallowing was studied in 13 young healthy adult subjects during the administration of graduated volumes of water (3, 10, and 20 ml). Simultaneous submental electromyography, respiratory plethysmography, and fiber-optic endoscopy revealed a well-timed pattern between physiological respiratory events and related swallowing events. Expiration was the phase of respiration that was most closely associated with deglutition. Respiration was usually maintained at the onset of deglutition and halted before the onset of laryngeal elevation. The apneic interval was approximately 1 s for the 3-, 10-, and 20-ml boluses. A large-volume (100-ml) straw swallow resulted in variable respiration-swallowing patterns and in statistically significant differences (P < 0.01) in the duration of apneic pause and laryngeal excursion. The expiratory phase of respiration resumed nearly 0.50 s before the completion of swallowing. Clinical implications of the findings are addressed and related to aspiration and pulmonary complications in dysphagic patients.

Clinical experience in 82 patients with pancreas divisum: preliminary results of manometry and endoscopic therapy.

Although it is clear that the majority of patients with pancreas divisum have no clinical disease, there is a subset of patients who have either unexplained abdominal pain or recurrent pancreatitis. Endoscopic therapy of the minor papilla may alter the clinical course of those patients with pancreas divisum and recurrent pancreatitis. Manometric study of the minor papilla is feasible and reveals a sphincter mechanism similar to the major papilla. Clinical response to endoscopic therapy may aid in selecting patients who might benefit from surgical sphincteroplasty. Refinement of manometric study of the minor papilla offers a potential method of detecting functional obstruction of dorsal duct drainage.