Effect of intravenous fat on cholecystokinin secretion and gallbladder motility in man.

During total parenteral nutrition (TPN) gallbladder bile stasis and hypomotility have been well documented. Little is known, however, about the effect of the separate components of TPN on gallbladder motor function. Inasmuch as fat, administered intraduodenally, is a potent stimulus of cholecystokinin (CCK) secretion and gallbladder contraction we have investigated whether intravenous (IV) fat affects gallbladder motility. Six healthy volunteers were studied on two separate occasions, during infusion of Intralipid 10%, 200 mL/h or saline infusion (control) for 3 hours, to evaluate the effect of IV infusion of fat on (1) plasma CCK concentration and gallbladder volume and (2) CCK-induced gallbladder emptying. Intravenous infusion of Intralipid resulted in significant increases in serum triglycerides from 0.9 +/- 0.1 to 5.1 +/- 1.3 mmol/L (at 90 min). During fat infusion no significant changes in plasma CCK and gallbladder volume were noted when compared with basal values or to the control experiment. During IV fat, concomitant infusion of 0.25, 0.5, and 1.0 Ivy dog unit (IDU) per kilogram per hour of CCK-33 resulted in a significant reduction in gallbladder volume from 26 +/- 6 cm3 (basal) to 15 +/- 4 cm3 (p less than .05), 6 +/- 2 cm3 (p less than .05) and 2.5 +/- 1 cm3 (p less than .05), respectively. No significant differences in CCK-induced gallbladder emptying were observed between IV fat and saline infusion (control). It is concluded that, in contrast to intraduodenal fat, IV infusion of fat does not affect (1) basal plasma CCK and gallbladder volume and (2) CCK-induced gallbladder contraction.     

Analysis of observed behaviors displayed by depressed patients during a clinical interview: relationships between behavioral factors and clinical concepts of activation.

In 61 drug-free depressed patients, relationships were studied between observed behaviors and measures of common clinical concepts of activation. The behaviors were observed during a clinical interview and analyzed with ethological methods. Activation was assessed by means of self-ratings (Thayer, AD-ACL) and global judgement (Hamilton, retardation, agitation). Various aspects of patients' speaking and listening behaviors were recorded and analyzed, such as looking, head movements, yes-nodding and no-shaking, leg movements, gesturing, and body and object touching. A factor analysis was applied, enabling grouping of behaviors without using a priori concepts. Five factors reflected different aspects of a conversation: restlessness (leg and hand movements), speech, active listening (head movements and intensive body touching, during listening), speaking effort (looking, gesticulating, head movements, during speaking), and eagerness (yes-nodding and no-shaking). Significant positive relationships were found between the speech factor, the speaking effort factor and the restlessness factor on the one hand, and activation on the other. The eagerness factor was related negatively with activation. The results give insight into the organization of behavior during an interview, and show how this is related to clinical concepts of activation.     

Non-invasive evaluation of hemodynamic, tremorogenic and biochemical effects in response to beta-adrenoceptor stimulation

1, 4, 12 and 24 micrograms SOM 1397 CL, a new beta 2-adrenergic bronchodilator, were administered by inhalation to 10 healthy volunteers in a double-blind, placebo-controlled, within-subject crossover study in order to assess circulatory, tremorogenic and biochemical effects. 1 microgram SOM 1397 CL did not cause any relevant changes in the measured parameters. After administration of 4 micrograms a slight but continuous increase in tremor amplitude and c-AMP was observed. The effects on hemodynamics and other laboratory values could be considered negligible. Overdoses of 12 and 24 micrograms resulted in a dose-dependent increase in systolic blood pressure, pulse rate, tremor amplitude, alpha-AMP and lactic acid, as well as in a decrease of diastolic blood pressure and potassium. These effects may be partly attributable to beta 2-receptor stimulation. The method described in this paper can be applied as a useful tool for determination of beta 2-adrenergic activity in healthy volunteers, independent of the conventional methods which are used to evaluate efficacy of bronchodilators by the degree of bronchial muscular relaxation.     

Multiple Implants for First Molar Prosthodontics

Problems that can occur when single implants are utilized to restore first molar teeth include the frequent loosening of screws, as well as screws and/or implant breakage. These may result from torquing and rotational movements of the prosthesis during masticatory and parafunctional mandibular movements. When sufficient bone and mesio-distal restorative space is present, the placement of two implants should be considered.     

High-capacity in vitro assessment of anti-hepatitis B virus compound selectivity by a virion-specific polymerase chain reaction assay.

An integrated assessment system specific for hepatitis B virus (HBV) Dane particle DNA was developed to examine the activity of potential anti-HBV compounds in chronic HBV-producing HepG2-derived 2.2.15 cells. Cell culture, immunoaffinity purification, polymerase chain reaction, and hybrid-capture detection were performed in the microtiter format to facilitate increased throughput by automation. The high sensitivity afforded by the assay provided quantitative detection of less than 0.5 fg of extracellular HBV DNA from 25 microliters of cell culture supernatants, and drug-induced reductions in HBV titers greater than 100-fold were easily measured. Fluorometric determination of total cellular DNA from the same 96-well proliferating cell cultures allowed simultaneous evaluation of inhibition of cell growth, thus providing the ability to assess the overall selectivities of candidate compounds in a single experiment. The potent activities of three anti-HBV compounds, the (+) and (-) enantiomers of cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxythiolane-5-yl]cytosine (FTC) and D-carbocyclic-2'-deoxyguanosine (CDG), were confirmed by this method. (-)-FTC was more active than its (+) enantiomer (50% inhibitory concentrations, 0.033 +/- 0.006 and 0.723 +/- 0.160 microM [standard error of the mean; SEM], respectively), while both enantiomers demonstrated a lack of cytotoxicity at 200 microM. CDG was more potent (50% inhibitory concentration, 0.0063 +/- 0.0007 microM [SEM]) but was also significantly more toxic, inhibiting cell growth by 50% at 32 +/- 6 microM (SEM). These results demonstrate the usefulness of this immunoaffinity-based, quantitative polymerase chain reaction system as a high-capacity in vitro tool for assessment of anti-HBV compound selectivity.     

Intraoperative fiberoptic angioscopy to evaluate the completeness of pulmonary embolectomy

Intraoperative angioscopy was performed in three patients who underwent pulmonary embolectomy for massive pulmonary embolism. Angioscopy followed conventional techniques such as extracting the clot by a gallstone forceps, using a Fogarty catheter in the pulmonary tree or squeezing of the lungs. The rationale for angioscopy was to assess the result of these usual "blind" techniques. In two patients residual thrombus was detected and removed under direct visual control. Our initial experience suggests that intraoperative angioscopy appears to be useful in the detection of residual thrombus material, especially in the asanguinous, arrested heart. The small size of the angioscope allows easily access to the secondary, and up to the tertiary pulmonary branches. Clots can be visualized and extracted under direct visual control.     

Hepatic,intestinal and renal transport of 1-naphthol-β-d-glucuronide in mutant rats with hereditary-conjugated hyperbilirubinemia

Summary Recently, a mutant rat strain was described with a genetic defect for the biliary excretion of organic anions (TR^– rats). To determine the possible heterogeneity of the transport systems in liver, intestine and kidney we investigated the transport of the anion 1-naphthol--d-glucuronide (1-NG) in isolated vascularly perfused organ preparations of the rat liver, intestine and kidney of both Wistar rats and TR^– rats. 1-NG was administered as such (liver and kidney experiments) or formed intracellularly from 1-naphthol (1-N) (liver and gut experiments). Independent of the type of exposure to 1-NG, the biliary excretion was considerably impaired in TR^– rats. In the intestine the total appearance and the vascular/luminal distribution pattern of 1-NG were not significantly different from the values in control rats. Furthermore, no significant disturbance was found with respect to the renal clearance of 1-NG in the TR^– rat when compared with the Wistar rat. Thus, the genetic defect in the TR^– rat is restricted to an impaired hepatobiliary excretion of 1-NG and does not affect the excretory systems of the intestine and kidney. These results suggest that the excretion of 1-NG by the liver, intestine and kidney involves distinct organ-specific transport systems.     

Hemicholinium-3 impairs spatial learning and the deficit is reversed by cholinomimetics

The effects of hemicholinium-3 (HC-3) on spatial discriminaton learning were studied. Rats were equipped with indwelling cannulae in the right lateral ventricle and, following recovery, were trained on a two platform spatial discrimination task in a water maze. In this task a visible escape platform remains in a fixed position in the pool during a single training session, whilst the location of an identical float (which affords no escape) is randomly varied. For each session the location of the fixed escape platform was changed and the rats were retrained to criterion following pretreatment either with artificial cerebrospinal fluid (CSF) or HC-3 (2.5, 5.0 g/rat/ICV) 1 h before training. Each rat received every treatment according to a latin square design. The results showed that spatial learning was dose dependently impaired by HC-3, choice accuracy being reduced to chance levels by the higher dose. There was no evidence of motoric difficulty, as choice latencies were not significantly increased. Experiments were then conducted to test for reversal of the deficit using a range of psychotropic drugs. Rats were treated with CSF or HC-3 (5 g/rat ICV) 60 min prior to testing and test drugs were injected 15 min before testing. Some doses of physostigmine (46–460 g/kg/SC) and tetrahydroaminoacridine (THA) (2.2–10 mg/kg/SC) reversed the spatial learning deficit. The muscarinic agonists arecoline (0.046–1 mg/kg/SC), aceclidine (1–10 mg/kg/SC), oxotremorine (30–100 g/kg/SC) and RS-86 (0.46, 1.0 g/kg/SC) were also effective. Pilocarpine (0.22–2.2 mg/kg/SC) showed marginal activity and isoarecoline (4.6–10 mg/kg/SC) was inactive. Nicotine (0.32, 1, 3.2 mg/kg/SC) and piracetam (10, 30, 100 mg/kg IP) were also inactive. The ₂ agonist, clonidine (46, 100 g/kg SC) and the antagonist idazoxan (32, 100 g/kg SC) were also inactive. Learning deficits were not reversed by haloperidol (20, 60 g/kg), amphetamine (0.1, 0.46 mg/kg), the selective 5-HT_1A agonist 8-OH-DPAT (30, 100 g/kg) or by the benzodiazapine antagonist ZK 93426 (1, 3.2, 10 mg/kg). The results show that forebrain Ach depletion by HC-3 impairs spatial discrimination learning and these deficits are reversed by cholinesterase inhibitors and some muscarinic receptor agonists. Some degree of pharmacological selectivity is indicated by the failure of a range of other drugs to reverse the impairments.     

Changes in Avidity and Level of Immunoglobulin G Antibodies to Mycobacterium tuberculosis in Sera of Patients Undergoing Treatment for Pulmonary Tuberculosis

Much is known about specific antibodies and their titers in patients with tuberculosis. However, little is known about the avidity of these antibodies or whether changes in avidity occur during the progression of the disease or during treatment. The aims of this study were to determine the avidity of antibodies to Mycobacterium tuberculosis in patients with pulmonary tuberculosis, to explore the value of avidity determination for the diagnosis of tuberculosis, and to study changes in levels of antibodies and their avidity during treatment. Antibody avidity was measured by an enzyme-linked immunosorbent assay with thiocyanate elution. Avidity indices and serum levels of immunoglobulin G to M. tuberculosis were determined for 22 patients with pulmonary tuberculosis before and during treatment and for 24 patients with other pulmonary diseases. Antibody levels and avidity were both significantly higher in untreated tuberculosis patients than in the controls. Avidity determination had more diagnostic potential than determination of the antibody levels. Tuberculosis patients with a long duration of symptoms had higher antibody avidity than those with a recent onset of symptoms, indicating affinity maturation of specific antibodies during active disease. In the early phase of treatment, a decrease in antibody avidity was observed for 73% of all tuberculosis patients, accompanied by an initial increase in antibody levels in 36% of these patients. These phenomena could be explained by an intense stimulation of the humoral response by antigens released from killed bacteria, reflecting early bactericidal activity of antituberculous drugs leading to the production of low-affinity antibodies against these released antigens.