EFFECT OF DIFFERENT FLOW PATTERNS ON THE WRIGHT RESPIROMETER

The problems of using the Wright respirometer for measurementsat small rates of flow associated with small volumes are discussed.Accuracy is very dependent on the wave form of the flow passingthrough it.     

Immunosuppressive Effects of Emodin: An In Vivo and In Vitro Study

Objective

We sought to investigate the immunosuppressive effects of emodin and its potential in vivo and in vitro mechanisms.

Methods

In vitro immunosuppressive effects of emodin were analyzed by its ability to suppress the response of human peripheral blood mononuclear cells to phytohemagglutinin (PHA) and to mixed lymphocyte culture (MLC). We examined changes in interleukin (IL)-2 and IL-4 in within MLC supernates. The in vivo immunosuppressive effects of emodin were analyzed using a skin transplantation model in mice. We also investigated the mean survival time (MST) and plasma IL-2 levels.

Results

In vitro experiments: Responses of mononuclear cells to PHA and MLC were suppressed by emodin treatment. Decreased production of IL-2 along with promoted secretion of IL-4 was also observed by emodin treatment during MLC. In vivo experiments: The emodin-treated group showed prolonged MST of skin grafts and decreased serum IL-2 production.

Conclusions

Emodin showed immunosuppressive activities both in vivo and in vitro. The potential immunosuppressive mechanism of emodin's may be suppression of lymphocyte proliferation and influences on cytokines.     

A New Magnetically Suspended Centrifugal Pump: In Vitro and Preliminary In Vivo Assessment

Abstract: To overcome problems derived from the shaft within the conventional centrifugal pump, we have been developing a new centrifugal pump, namely a magnetically suspended centrifugal pump (MSCP), which has no shaft and operates as a noncontacting and bearingless pump. The impeller is suspended magnetically between the magnetic bearing and the driving motor. Hemolysis tests were performed in comparison with the Biopump (BP80, BioMedicus). The index of hemolysis (IH) was significantly lower in the MSCP than in the Biopump. In addition, a smaller gap in the MSCP induced lower hemolysis. In preliminary studies using mongrel dogs, the layer of thrombus adherent to the impeller was observed in a few hours, which impaired the pumping efficiency. However, by using an impeller coated with silicone, no aggregations of platelets or fibrin on the impeller were observed in 24 h of continuous pumping. In conclusion, the MSCP had a gentler influence on blood cells than the Biopump, and the impeller coated with silicone may contribute to the long-term pumping of the MSCP.     

INTERACTION BETWEEN THIOPENTONE AND SODIUM VALPROATE: An In Vitro and In Vivo Study

The effect of sodium valproate on the binding of thiopentoneto serum protein was studied in vitro. In the absence of valproatethe unbound fraction of thiopentone was 15.2±0.64%, butwith concentrations of valproic acid in excess of the therapeuticrange, it increased to 22.42±1.65%. Scatchard plots forthiopentone in the absence and presence of valproate were investigatedalso. The barbiturate was bound by one group of binding siteswith the association constant, K₂ = 2.81 x 10³ litre mol^–1and the number of binding sites (n) = 2.3. There was a markeddecrease in this association constant in the presence of valproicacid (K_a = 1.82 x 10^* litre mol^–1), but without significantchange in the number of binding sites (n = 2.13). Additionally,the effect of administration of sodium valproate i.v. on thiopentoneanaesthesia was examined in rabbits. The recovery time fromthiopentone was markedly longer in the presence of the anticonvulsantdrug (17.0 min v. 37.1 min).     

THE "STOVE-IN" CHEST: ANOTHER APPROACH TO TREATMENT

A case of "stove-in" chest is described in which the drug R1406(phenoperidine), a powerful analgesic and respiratory depressant,was used to allow the easy application of a mechanical ventilatorafter initial surgical fixation of the flail segment. It wasnoted that, under the influence of the drug, ventilation inparticular was adequate, and management in general relativelyeasy compared with previous cases. Undesirable side effectssuch as emesis and hypotension were not observed.     

In Vivo Effects on Spermatogenesis and In Vitro Metabolism of 5α-Androstan-3β,17β-Diol by Testes, Prostate Glands and Seminal Vesicles

It has been shown that 17β-hydroxy-5α-androstan-3-one (dihydrotestosterone, DHT), an irreversible metabolite of testosterone, is capable of maintaining spermatogenesis and sex accessory organs of adult rats. The same property has been displayed by 5α-androstan-3α,17β-diol (3α-diol). We have studied the effects of 5α-androstan-3β,17β-diol (3β-diol) in hypophysectomized rats. This steroid is also capable of maintaining spermatogenesis as well as the accessory glands of hypophysectomized rats. These effects of 3β-diol are quantitatively better than with 3α-diol. Incubation of teased testicular tissue, prostate glands and seminal vesicles with tritiated 3β-diol showed that 3β-diol is preferentially converted to 3α-diol in the testis and DHT in the prostate glands but is not metabolized by the seminal vesicles. This would tend to indicate that the biological activity may be attributed to any one of the 5α-reduced metabolites since the testes and prostate glands can metabolize 3β-diol and the seminal vesicles could get the appropriate form of the steroid by conversion at a peripheral site with transport to the seminal vesicles. Incubation of testicular tissue with tritiated 3β-diol and a steroidal inhibitor of 3β-hydroxysteroid dehydrogenase showed 90% inhibition of 3β-diol metabolism. In vivo studies with this inhibitor are underway to assess if 3β-diol is biologically active without being converted to other steroids.     

CONTINUOUS EXTRADURAL ANALGESIA IN LABOUR: Comparison Between "On Demand" and Regular "Top-up" Injections

In a prospective comparative study 240 patients received extraduralbupivacaine, either by regular timed injections or "on demand",for pain relief during the first stage of labour. Three concentrationsof bupivacaine were used (0.5%, 0.375% and 0.25%). Quality andcontinuity of analgesia, motor blockade, spread of sensory blockade,cardiovascular changes, fetal outcome and maternal sequelaewere recorded. Overall, the analgesia provided by regular top-upinjections was superior to the on demand technique, especiallywhen 0.375% bupivacaine was used. This improved analgesia wasachieved without causing an increased incidence of operativedeliveries or deleterious sequelae, with respect to the motheror the neonate.     

An External Aortic Root Device for Decreasing Aortic Regurgitation: In Vitro and In Vivo Animal Studies

Objectives: The purpose of this study was to determine if a device placed externally around the aortic root decreases regurgitant flow in acute aortic regurgitation. Background: Aortic regurgitant flow is dependent on central aortic pressure and the aortic root and leaflet geometry. It may be possible to decrease aortic regurgitant severity by reducing aortic root size or dimension changes. Methods: Aortic regurgitation was created in eight calf heart specimens suspended in a continuous flow system. Retrograde and antegrade aortic flow and distending aortic pressure were measured at baseline and after placement of an external aortic device at the level of the aortic annulus. In two additional specimens, the incompetent aortic valve was visualized fiberoptically before and after placement of the external device. Acute aortic regurgitation was created surgically in four live calves by excising a portion of the aortic leaflets. Antegrade and retrograde flow, left ventricular pressure, and central aortic pressure were measured at baseline, after creation of aortic regurgitation, and after placement of the external device. Results: In the in vitro calf specimens, regurgitant flow decreased from 46.9 cc/sec to 15.1 cc/sec (66.0%± 21.8% decrease) after placement of the external device (p < 0.001). The regurgitant orifice area decreased from 0.13 ± 0.04 cm² to 0.04 ± 0.02 cm² after device placement (p < 0.001). Antegrade flow was reduced to a smaller extent (20.0%± 19.2% decrease) by the device (p < 0.05). Placement of the device around the aorta resulted in improved coaptation of the leaflets with a marked reduction in defect size by endoscopic visualization. Use of the external aortic device was associated with improvement in aortic regurgitant severity in three of four calves with surgically created aortic regurgitation. Concluslons: In these preliminary studies, acute experimental aortic regurgitant severity is decreased by the use of an external aortic device, probably due to reduction in aortic annular dimension changes and improved aortic leaflet apposition. Further studies are needed to determine the effectiveness of this device in chronic aortic regurgitation. (J Card Surg 1994;9:304–313)     

Flow Characteristics of the St. Jude Prosthetic Valve: An In Vitro and In Vivo Study

The St. Jude cardiac prosthetic aortic valve was evaluated in vitro and in vivo in an attempt to establish flow characteristics and to correlate them with clinical findings. In vitro, a fluid vehicle (6% Polyol V-10, 32°C) with viscosity similar to blood (0.035 dyne-sec/cm²) was used under conditions of steady flow through a flow chamber simulating the aortic root. Gradient, velocity, and shear stress were measured 5.79 mm, 26.79 mm, 44.79 mm, and 77.79 mm downstream from 25-mm and 27-mm valves using a laser-Doppler anemometer. At 417 ml/sec, the valve gradient was 6.2 mmHg with the 25-mm valve, and 5.2 mmHg with the 27-mm prosthesis. Velocity was maximum at the orifice center, and wall shear stress was low (maximum 600 dyne/cm²). In vivo, six patients with 25-mm St. Jude aortic valves were studied within 48 hours after surgery to determine cardiac output, valve flow, and gradient. The gradient was 3.3 ± 1.9 mmHg (M ± SD) at 249 ± 96 ml/sec and the effective valve area was as large as the geometric area (2.58 vs. 3.09 cm²). Thus, flow through the St. Jude valve is unobstructed and central, has low turbulence, and achieves optimal effective valve area for a given available orifice area.     

Successful Transtracheal Lung Ventilation Using a Manual Respiration Valve: An In Vitro and In Vivo Study

Background: Lung ventilation through a thin transtracheal cannula may be attempted in patients with laryngeal stenosis or "cannot intubate, cannot ventilate" situations. It may be impossible to achieve sufficient ventilation if the lungs are spontaneously emptying only through the thin transtracheal cannula, which imposes high resistance to airflow, resulting in dangerous hyperinflation. Therefore, the authors describe the use of a manual respiration valve that serves as a bidirectional pump providing not only inflation but also active deflation of the lungs in case of emergency transtracheal lung ventilation.

Methods: The effectiveness of such a valve was tested in vitro using mechanical lungs in combination with two different cannula sizes and various gas flows. The valve was then tested in five pigs using a transtracheal 16-gauge cannula with three different combinations of inspiratory/expiratory times and gas flows and an occluded upper airway.

Results: In the mechanical lungs, the valve permitted higher minute volumes compared with spontaneous lung emptying. In vivo, the arterial oxygen and carbon dioxide partial pressures increased initially and then remained stable over 1 h (arterial oxygen tension, 470.8 +/- 86.8; arterial carbon dioxide tension, 63.0 +/- 7.2 mmHg). The inspiratory pressures measured in the trachea remained below 10 cm H2O and did not substantially influence central venous and pulmonary artery pressures. Mean arterial pressure and cardiac output were unaffected by the ventilation maneuvers.     

CRICOID PRESSURE WITH OR WITHOUT THE "CRICOID YOKE"

The performance of cricoid pressure was studied in three groupsof medical personnel likely to be involved in its applicationusing the cricoid yoke and a test rig. The instrument enabledindividuals who had no previous experience in the applica-tionof cricoid pressure to achieve results as good as those obtainedby experienced anaesthetic staff. Furthermore, the instrumentimproved the consistency of the applied force in all groups,particularly if cricoid pressure was required for sustainedperiods of 30 s or more.     

DIFFICULT LARYNGOSCOPY--THE "ANTERIOR" LARYNX AND THE ATLANTO-OCCIPITAL GAP

The atlanto—occipital distance is the major factor whichlimits extension of the head on the neck. It varies widely inthe population at large. When the posterior tubercle of theatlas is already in contact with the occiput in the neutralposition, attempts to extend the head result in anterior bowingof the cervical spine, and forward displacement of the larynx.This may be a cause of difficult laryngoscopy.     

Dialyzer Ultrafiltration Coefficients: Comparison Between In Vitro and In Vivo Values

This study describes a simple, convenient method for the in vivo measurement of the ultrafiltration coefficient of hemo-dialyzers. The method is based on a scheme of isolated ultrafiltration, i.e., ultrafiltration without dialysate flow through the dialyzer. Results with this method indicate that it is more accurate than the conventional bed scale technique. Measurements on three different dialyzers demonstrate that the in vivo ultrafiltration coefficient is only between 1% and 10% lower than the corresponding in vitro value. This is in contrast to the rule of thumb used by some manufacturers that in vivo coefficients are 30% lower than in vitro values. The deviation of the in vivo value from the in vitro one seems to be higher with higher dialyzer ultrafiltration coefficients. Based on these results, it is recommended that to estimate ultrafiltration ratres in the clinical setting, the in vitro ultrafiltration coefficient be used, transmembrane pressures being corrected for the colloid osmotic pressure of plasma proteins.     

Taurolidine Inhibits Tumor Cell Growth In Vitro and In Vivo

Background: Taurolidine, a derivative of the amino acid taurine, exhibits antiendotoxin, antibacterial, and antiadherence activity. We hypothesized that Taurolidine may inhibit tumor cell growth, both in an in vitro and in vivo setting. Our aim was to examine the effect of Taurolidine on the growth of a rat metastatic colorectal tumor cell line (DHD/K12/TRb) in vitro and in vivo.Methods: In the in vitro experiments, DHD/K12/TRb cells were incubated with 5, 10, 15, 25 g/ml of Taurolidine. Cells incubated in culture medium alone were used as controls. Cell proliferation, cell viability, cell death, and cell apoptosis were measured using commercially available techniques. In the in vivo experiment, BD IX rats were randomized into two groups (n = 10/group). Group A (control) underwent laparotomy and instillation of DHD/K12/TRb tumor cells intraperitoneally followed by phosphate buffered saline (PBS). Group B received Taurolidine (100 mg/kg) instead of PBS. Animals were killed after 24 days and tumor burden assessed by counting the number of tumor nodules in the peritoneal cavity.Results: Incubation of the tumor cells with Taurolidine resulted in a 4-fold decrease in proliferation rates (25 ± 4% vs. 100 ± 28% for controls) and a 4-fold increase in cell necrosis as demonstrated by the increase in LDH release (403 ± 28% vs. 100 ± 26% for controls), at a Taurolidine concentration of 25 g/ml. A dose-dependent decrease in cell viability was also observed. In the in vivo study, local Taurolidine administration resulted in significant decreases in tumor burden (3 ± 1 nodules in Group B animals vs. 649 ± 101 nodules in Group A animals).Conclusions: Taurolidine inhibits the growth of a rat metastatic colorectal tumor cell line in vitro and in vivo and thus may have potential in the prevention of peritoneal metastases.     

METHAEMOGLOBINAEMIA FOLLOWING THE USE OF PRILOCAINE ("CITANEST")

A series of eighty-one consecutive cases is reported in whichcontinuous lumbar epidural block was performed on women in labour,prilocaine (Citanest) being the agent used. Nine cases showedcyanosis, and in seven of these spectroscopic examination ofthe blood showed methaemoglobinaemia. The relationship of prilocaineto aniline derivatives, known to cause methaemoglobinaemia,is mentioned.     

Pharmacokinetics of Certoparin During In Vitro and In Vivo Dialysis

The efficacy and safety of certoparin in the prophylaxis of clotting during hemodialysis have recently been proven. Different to other low‐molecular weight heparins (LMWHs), certoparin does not accumulate in maintenance dialysis patients for unknown reasons. The purpose of the present study was to examine the impact of the dialysis procedure on the removal of certoparin. In a subgroup of the MEMBRANE study consisting of 12 patients, the pharmacokinetics of certoparin during hemodialysis was determined by means of the anti‐Xa activity. In addition, the elimination of certoparin into continuously collected dialysate was assessed. Further, in vitro experiments with human blood‐simulating high‐flux hemodialysis and hemofiltration were performed to quantify the elimination and the sieving coefficients S_K of the two LMWHs certoparin and enoxaparin compared with unfractionated heparin (UFH). The surrogate marker middle molecules inulin and myoglobin served as reference solutes during the experiments. Finally, the adsorption of ¹²⁵iodine‐radiolabeled certoparin onto the synthetic dialysis membrane was quantified. The clinical study reconfirmed the absence of bioaccumulation of certoparin with anti‐Xa activities between <0.01 and 0.02 IU/mL after 24 h. A short plasma half‐life time of 2.0 ± 0.7 h was determined during hemodialysis. Of the total certoparin dose injected intravenously prior to hemodialysis, only 2.7% was eliminated into dialysate. The in vitro experiments further revealed only 6% of certoparin to be adsorbed onto the dialysis membrane. The anti‐Xa activities of certoparin and enoxaparin slowly declined during in vitro hemofiltration to 87.3 ± 5.5 and 82.5 ± 9.4% of baseline, respectively, while inulin and myoglobin concentrations rapidly decreased. The anti‐Xa activity of UFH remained unchanged. The S_K of both LMWH and UFH was very low in hemofiltration and particularly in hemodialysis with values ≤0.1. The elimination kinetics during hemodialysis suggests strong protein‐binding of certoparin. Different from LMWH significantly cleared by the kidneys, the relatively short half‐life time of certoparin of only 2 h during hemodialysis allows a more reliable control of the anti‐coagulatory effects and decreases the risk of bleeding complications. Dialytic removal does not significantly contribute to the clearance of certoparin in maintenance dialysis patients.     

ACUTE "TOLERANCE" TO THE CENTRAL RESPIRATORY EFFECTS OF MIDAZOLAM IN THE DOG

The effect of repeated doses of midnTinlam 0.1 mg kg^–1on efferent activity in the phrenic nerve was observed in sevenartificially ventilated dogs, anaesthetized with chloraloseand paralysed with suxamethonium. PaO₂, .PaCo₂ arterial pH andcore temperature were adjusted to constant values throughouteach experiment. The first dose of midazolam caused a relativelyprolonged reduction in phrenic activity, after complete recoverya second dose was administered and so on for four doses. Peakphrenic efferent activity returned to initial values on average69 4min after the first dose of miHnTnlam The effects of successivesubsequent doses lasted progressively shorter times (mean values49.4, 38.7 and 25.3min). In four preparations, 2 h after recoveryfrom the fourth doses a second "train" of four doses was administered.The response to the first dose of this second "train" showedthat 90% recovery had occurred from the effect of the first"train" and there wts a similar sequence of decreasing responsesto successive doses. This study demonstrated acute toleranceto the central respiratory effects of midazolam. ^*Present address: Department of Anaesthetics, Brompton Hospital,Fulham Road, London SW3 6HP.     

An In Vitro and In Vivo Study of Cytokines in the Acute-Phase Response Associated with Bisphosphonates

We studied the acute phase response, including specific cytokine production, [interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor α(TNFα)] following a single dose of Aredia (disodium pamidronate) in patients with increased bone turnover and, in vitro, the role played by specific cytokines in the acute-phase reaction which may follow the administration of aminobisphosphonates. An in vivo exploratory study was done on 24 in- and outpatients with increased bone turnover given a single intravenous dose of pamidronate 60 mg. Measurements were taken at baseline and at 24, 48, and 72 hours. The main outcome measures were changes from baseline in serum IL-1, IL-6, and TNFα. In addition, C-reactive protein (CRP), white blood cell count (WCC), lymphocyte count, and elastase concentration were measured. Symptomatic evaluation was made of fever, bone pain, and rigors. In vitro, whole blood from eight healthy volunteers was exposed to various concentrations of the three bisphosphonates—pamidronate, clodronate, and zoledronate. Measurements were taken immediately before and at 3, 6, and 10 hours after exposure to drugs. The main outcome measures were changes in serum IL-1, IL-6, and TNFα. In vivo, there was a statistically significant (P < 0.001) increase in median values of TNFα in all post-baseline measurements. Median values for IL-6 also showed a significant (P < 0.001) increase at 24 hours after dosing. There were no statistically significant changes in median IL-1 values. Few patients showed any change from baseline in total WCC or in lymphocyte count, but 62.5% of patients with normal range baseline values for CRP increased to above normal levels after treatment. Fourteen patients experienced fever; 2 reported rigors. There was no correlation between fever and changes in cytokines. There were no serious adverse experiences or premature discontinuations due to poor tolerability, and 91% of the patients expressed willingness to receive pamidronate again. In vitro, an increase in TNFα and a mild increase in IL-6 was seen with all bisphosphonates, with the greatest effects seen with the highest concentration of both pamidronate and zoledronate. No changes were observed in IL-1 with any agent. Significant changes in both TNFα and IL-6 were observed within 3 days of a single dose of pamidronate in patients treated for the first time confirming previous findings. However, the lack of change in IL-1 in vivo and in vitro does not support the hypothesis that this cytokine plays a major role in the acute phase reaction. The cellular mechanism of the interaction among aminobisphosphonates, Il-6, and TNFα requires further investigations. The results of the in vitro study are consistent with the in vivo findings. Received: 30 September 1996 / Accepted: 21 May 1997     

CONGENITAL FIBRO-OSSEOUS DYSPLASIA OF JAWS ("HIPPOPOTAMUS FACE"): An anaesthetic problem

Two brothers with "hippopotamus face" deformities presentedfor corrective surgery under general anaesthesia. In the firstpatient, blind nasal intubation was successful. In the secondpatient, trache otomy was avoided by the use of an intubatingbronchoscope.