Mandibular elongation by automatic distraction osteogenesis: the first application in humans.

We report the case of a 65-year-old man who was the first person to have the right ramus of his mandible lengthened by 20mm by automatic continuous distraction osteogenesis. The device consists of two units: a component that is implanted into the bone, and an external component that is distant from the surgical site and mounted on a battery-driven portable syringe driver or infusion pump. A non-compressible drive cable connects the two.

The time-dependent mechanical properties of skin.

The mechanical properties of the skin were investigated by applying a torsional deformation to a circumscribed area. Results of the tests indicate that the skin is nonlinear and time dependent. The dynamic response shows that the phase angle is insensitive to frequency below 1 Hz; the peak torque amplitude increases slowly above 0.004 Hz. A self-consistent description is presented utilizing continuous relaxation spectra. The technique describes the stress relaxation data and predicts the form of the dynamic response.

Dipyridamole inhibits red cell-induced platelet activation.

We have recently shown that red blood cells can induce spontaneous platelet aggregation (SPA) in whole blood ex vivo, which could be inhibited by dipyridamole. Since this drug, at therapeutic doses is not an effective inhibitor of platelet aggregation in platelet rich plasma, the inhibition of platelet interaction with the red cell was thought to be the mechanism of its action. Values for the percentage fall in the single platelet count due to SPA in whole blood after 3 and 6 min rollermixing were: control 15 +/- 2.2 and 42 +/- 2.9; 6 microM dipyridamole 6 +/- 1.1 (P less than 0.001) and 31 +/- 2.6 (P less than 0.01); 12 microM dipyridamole 2 +/- 0.9 (P less than 0.0005) and 22 +/- 2.3 (P less than 0.0005) (mean +/- SEM, n = 10). Electron microscopic observation revealed that the aggregation involves an initial platelet adhesion to the red blood cell; the adherent platelets then become activated and serve as foci for the growing aggregates. Dipyridamole appeared to inhibit the initial platelet adhesion to the red cell (the principal trigger mechanism for SPA) which may mimic the initiation of thrombosis in some situations in vivo. The inhibitory effect of dipyridamole on the platelet-red cell interaction suggests that this drug has antithrombotic potential in situations where red blood cells have a trigger role in platelet activation and may explain why the drug has been more effective in some situations than in others.

Red blood cells mediate spontaneous aggregation of platelets in whole blood.

The influence of red blood cells on spontaneous platelet aggregation (SPA) has been studied ex vivo. Platelet aggregation was quantified by measuring the fall in single platelet count using a new whole blood platelet counter. When aliquots of whole blood and autologous platelet rich plasma (PRP) were roller-mixed at 37 degrees C, a marked fall in platelet count occurred in whole blood due to SPA but platelet count remained almost unchanged in PRP. When blood from healthy young controls, aged 20-35 years, was compared with healthy old controls, aged 48-80 years, and patients with thrombotic complications, the extent of SPA was in the order: thrombotic patients greater than old controls greater than young controls. Prostacyclin and the new stable prostacyclin analogue Iloprost, at 8 nM effectively inhibited SPA. 2-Chloroadenosine (10 microM) which is an inhibitor of ADP-induced platelet aggregation was also an effective inhibitor of SPA. Acetylsalicylic acid (56 microM) and the thromboxane A2 receptor blocker BM13.177 (0.5 microM) only partially inhibited SPA. ADP from red blood cells is suspected to mediate red cell-induced SPA. However, the possibility that the red cells have an important physical role in SPA cannot be ruled out.

Effect of dipyridamole on spontaneous platelet aggregation in whole blood decreases with the time after venepuncture: evidence for the role of ADP.

Spontaneous platelet aggregation (SPA) was studied in human whole blood at 3, 5, 10, 20, 30, 40, and 60 minutes after venepuncture. Using a whole blood platelet counter, SPA was quantified by measuring the fall in single platelet count upon rollermixing aliquots of citrated blood at 37 degrees C. The extent of SPA increased with the time after venepuncture, with a correlation coefficient of 0.819. The inhibitory effect of dipyridamole (Dipy) on SPA was studied: (a) 10 microM at each time interval; (b) 0.5-100 microM at 3 and 30 minutes and (c) 15 microM in combination with 100 microM adenosine, 8 microM 2-chloroadenosine (2Clad, an ADP receptor blocker) and 50 microM aspirin. There was a rapid decrease in the inhibitory effect of Dipy with the time after venepuncture; the correlation coefficient was -0.533. At all the concentrations studied, Dipy was more effective at 3 minutes than at 30 minutes after venepuncture. A combination of Dipy with adenosine, 2ClAd or aspirin was a more effective inhibitor of SPA than either drug alone. However, when 15 microM Dipy and 10 microM Ad were added together, the inhibitory effect of Dipy was not increased significantly, suggesting that Dipy inhibits platelet aggregation independent of Ad. The increase in SPA with the time after venepuncture was abolished when blood was taken directly into the anticoagulant containing 5 microM 2ClAd. It is suggested that ADP released from the red blood cells is responsible for the increased platelet aggregability with the time after venepuncture and makes a serious contribution to the artifacts of in vitro platelet function studies.

A comparison of spontaneous platelet aggregation in whole blood with platelet rich plasma: additional evidence for the role of ADP.

ADP, generated from red blood cells is believed to be responsible for the spontaneous aggregation of platelets in whole blood. This notion is based mainly on the use of enzymes which remove ADP. We have studied spontaneous platelet aggregation in whole blood and autologous platelet rich plasma obtained from 12 healthy male and female volunteers. Platelet aggregation was quantitated by measuring the fall in the number of single platelets counted using a whole blood platelet counter (Ultra Flo 100). In a rotating tube model, the mean fall in the number of platelets due to spontaneous aggregation was 56% in whole blood but, only 3% in platelet rich plasma prepared from the same blood samples. Spontaneous platelet aggregation in whole blood was unaffected by apyrase grade I, but was reduced to 15% by apyrase grade II, to 38% by creatine phosphokinase/creatine phosphate and to 9% by pyruvate kinase/phosphoenolpyruvate. The results of this study provide additional evidence that ADP generated in whole blood triggers the spontaneous aggregation of platelets.

A critical investigation into the existence of circulating platelet aggregates.

By a method of counting single platelets in diluted whole blood, platelet aggregates were quantified ex-vivo. Four groups: 20 thrombotic patients, 10 non-thrombotic patients, 10 healthy old controls and 10 healthy young controls were included in the study. Using a 19 gauge needle, with and without tubing, venous blood was taken into buffered EDTA, as a disaggregating agent and buffered EDTA-formalin, as the fixative. The amount of platelet aggregates quantified was affected by the quality of venepuncture or the rate of blood flow through the needle, but was unaffected by the presence of the tubing. There was no statistically significant difference between the four groups, in terms of the platelet aggregates quantified, but scanning electron microscopy revealed the presence of irreversible aggregates, composed of platelet red and white blood cells, in the blood of a greater number of thrombotic patients than non-thrombotic or healthy controls. Platelet aggregates were also quantified in aliquots of platelet rich plasma, and were found to be significantly greater than the corresponding values in whole blood. The difference appeared to be due to increased viscosity of the plasma, induced by the fixative which reduces platelet mobility during centrifugation. It is concluded that the platelet aggregates which disaggregate in buffered EDTA may represent an artifact of blood collection; the irreversible aggregates are suspected to represent the in vivo circulating aggregates.

The novel effect of a new prostacyclin analogue ZK36374 on the aggregation of human platelets in whole blood.

Platelet aggregation was studied at 37 degrees C in citrated whole human blood, using the Ultra Flo 100 Whole Blood Platelet Counter. Aggregation was measured as a fall in the number of single platelets following addition of an aggregating agent. At peak aggregation, the fall in the number of platelets induced by ADP (10 microM), collagen (1 microgram/ml) or thrombin (0.2 U/ml) was about 90%. When blood was incubated with the prostacyclin-analogue ZK36374, the aggregation responses to ADP, collagen and thrombin were reduced with IC50's = 0.5, 1.5 and 3 nM respectively and the corresponding IC100's were: 1, 3 and 12 nM. When ZK36374 was added at peak aggregation, the number of single platelets increased significantly due to disaggregation of preformed platelet aggregates. It is concluded that the present technique represents a rapid, sensitive and more physiological approach for investigating the effects of pharmacological agents on platelet aggregation.

Subcutaneous ancrod after operation for fractured hip--a dose-ranging and feasibility study.

We have conducted a dose-ranging and feasibility study of daily subcutaneous injections of ancrod (Arvin) as a potential antithrombotic method in 28 patients following operation for fractured neck of femur. Sustained, predictable fibrinogen depletion during the first post-operative week was induced by four different regimes. A total dose of 10 units/kg weight, given in divided doses starting on the day of operation, is suggested as a possible antithrombotic regime. Ancrod treatment produced a rise in fibrinogen/fibrin degradation products, prolongation of the thrombin clotting time, and a fall in plasminogen, plasma fibrinogen and corrected blood viscosity were observed in 14 control patients. Plasma fibrinogen was correlated with plasma viscosity and corrected blood viscosity. No adverse effects of treatment occurred. Subcutaneous ancrod appears to be a simple, safe, and feasible potential antithrombotic method, and merits trials of efficacy in the prevention of post-operative thromboembolism.

Mechanics of native bovine pericardium. I. The multiangular behaviour of strength and stiffness of the tissue.

Native bovine pericardial samples have recently been reported to be mechanically anisotropic in both biaxial and uniaxial tests. We present results of multiangular tensile tests conducted on strips from native pericardial samples. These tests were needed in order to establish the nature of the anisotropy, in other words identify the class of the material symmetry. We also examine the possibility of describing the multiangular behaviour of the ultimate tensile stress and stiffness of the tissue by using a theory pertinent to composite structures comprised of linear elastic elements. This application was in general successful and should contribute towards a better understanding of the mechanics and deformations of natural materials with a woven fabric (structure).

Mechanics of native bovine pericardium. II. A structure based model for the anisotropic mechanical behaviour of the tissue.

A constitutive law to describe the mechanical behaviour of native bovine pericardial samples is proposed. The model is based upon an idealization of the tissue structure and in particular makes use of the preferential orientation of the collagen and elastin fibres in the plane of the tissue along a mechanically predominant direction. This non-axisymmetric layout of the tissue fibres has been shown in the past to cause a systematic variation of the tensile strength and the stiffness with the angle of orientation. The proposed constitutive relation provided a very good fit for results collected along two orthogonal principal directions in the past in uniaxial and biaxial tensile testing modes. It also allowed a better understanding of the interaction of the various load bearing elements and was able to describe some strange features of the tissue's anisotropic mechanical behaviour.

Mobility of elderly patients in bed. Measurement and association with patient condition.

Measurements were made of the overnight mobility of a group of elderly hospital patients whose clinical status had been assessed using the Norton clinical assessment score. The number of movements on the first two nights after admission differed from subsequent nights. There was a significant correlation between mobility and patient condition on all nights except the second. Patients assessed as being at high risk of developing pressure sores made fewer movements; mobility criteria are presented for detecting these individual patients.

An assessment of red cell deformability using a simple filtration method.

We assessed the simple method of measuring red cell deformability described by Reid et al. The technique was found to be reproducible. The validity of the method as a measure of red cell deformation was confirmed by (a) marked reduction of the deformability index after fixation of red cells with glutaraldehyde, and (b) an inverse correlation of deformability index with high-shear blood viscosity (r = 0.4; P < 0.001). There was no correlation of deformability index with low-shear blood viscosity, plasma viscosity, fibrinogen, or the white cell count. In normal subjects, deformability index was similar in males and females, and in smokers and non-smokers. Patients with acute myocardial infarction, or intermittent claudication, had reduced deformability compared to controls (P < 0.01).

Platelet aggregation studies in whole human blood.

Since the development of the photometric aggregometer, platelet aggregation studies are routinely performed on platelet-rich plasma (PRP). We have studied platelet aggregation in fresh citrated whole human blood using the recently developed Ultra Flo 100 Whole Blood Platelet Counter. Aggregation of platelets in whole blood was induced with adenosine 5'-diphosphate (ADP; 0.25-10 microM), collagen (0.25-1.0 microgram/ml) and thrombin (0.05-0.2U/ml). Platelet aggregation induced by ADP and thrombin was maximum within 1 min, and that of collagen within 3 mins. Aggregation responses to low concentration of ADP and thrombin were rapidly reversible, whereas responses to collagen and high concentrations of ADP and thrombin were virtually irreversible. The aggregation of platelets was indicated by a fall in platelet count; confirmed by scanning electron micrographs which revealed the presence of large aggregates of platelets, and was prevented when blood was treated with EDTA as anticoagulant. The present technique appears to be rapid, sensitive and reliable; and allows direct measurement of platelet aggregation and disaggregation in whole blood in vitro and ex-vivo.

Further studies on the role of red blood cells in spontaneous platelet aggregation.

The influence of red blood cells on platelet aggregation has recently been a subject of considerable interest. We have studied the effect of red cells on spontaneously formed platelet aggregates in rotating vials at 37 degrees C. Platelet aggregation was quantified by measuring the fall in number of single platelets with a whole blood platelet counter. Autologous packed red cells, platelet rich plasma and platelet free plasma were used to reconstitute aliquots of blood with constant platelet count but 0-60% haematocrit (Hct). The fall in platelet count was minimal at zero Hct, increased markedly with the Hct in the anaemic range and less markedly in the normal to polycythaemic ranges of Hct. Scanning electron microscopic observation of whole blood showed the presence of small platelet aggregates after about 3 mins rotation and very large aggregates after about 12 mins. ADP from red cells has been implicated in triggering platelet aggregation in whole blood. Whether aggregates are formed as a result of ADP leaking from the red cells or by their jostling physical action on the platelets is discussed. The marked effect of the red cells on spontaneous platelet aggregation however, justifies the manipulation of the Hct as a useful therapeutic option in the control of thrombotic and bleeding tendencies.

The influence of model parameter values on the prediction of skin surface temperature: II. Contact problems.

A model of heat transfer and temperature distribution in the skin and superficial tissues which is based on a finite difference numerical solution of the one-dimensional multilayer coupled bioheat equation is presented. The model is used to investigate the influence of the values chosen to represent the physiological and thermal properties of the tissues on the skin surface temperature after contact with an external medium. It was found that the skin blood flow and dermal conductivity were the main cutaneous parameters which influence the contact response, but in terms of normalized temperature the response was little influenced by cutaneous metabolic heat generation and deep dermal temperature. For contact with a good conductor, the transient behaviour was sensitive to the heat transfer coefficient on the outer surface and the thickness of the contact material, but insensitive to the conductivity of the material.

The influence of model parameter values on the prediction of skin surface temperature: I. Resting and surface insulation.

A model is presented of heat transfer and temperature distributions in the skin and superficial tissues. It is based on a finite difference numerical solution of the one-dimensional multilayer coupled bioheat equation. In this paper, the model is used to investigate the influence of the values of parameters chosen to represent the physiological and heat transfer processes on the temperature of the skin under resting conditions and after insulation of the skin surface. Equilibrium resting temperatures were strongly influenced by deep body temperature especially at lower heat transfer coefficients on the skin surface, but slightly affected by the values chosen for skin blood flow and metabolic heat generation; both the heat transfer coefficients and environmental temperature strongly influenced the surface temperature. After surface insulation the temperature elevation was strongly influenced by the thermal conductivities of tissues, skin blood flow and deep boundary temperature; metabolic heat generation was only significantly at unphysiologically high values.

Modelling transient heat transfer through the skin and a contact material.

Two thermal models of the skin and superficial tissues are described, both of which incorporate the thermal effects of subcutaneous and dermal blood flow through temperature-dependent heat sources. The model which represents the dermal blood flow as the perfusion of a region of finite thickness gives rise to purely numerical solutions for the transient temperatures. Representing the dermal blood flow by a heat generating surface gives rise to a model which yields explicitly analytical expressions. Although these analytical expressions require numerical integration techniques to finally evaluate them, they are of a form which allows temperature values to be derived more efficiently than by the purely numerical method. Both models are used to predict the time-dependent temperature profiles resulting from the interaction between the tissues and thermally passive materials in intimate contact with the skin surface. The predictions of the two models are compared and the limitations of the analytical model highlighted.

Mechanical and failure behaviour of the stratum corneum.

The load-deformation-time behaviour of heat-separated human stratum corneum was investigated using a pure shear specimen geometry. The tissue displayed non-linear load-deformation behaviour and stress relaxation, although the extensibility and amount of stress relaxation was considerably less than that shown by other soft connective tissues. Controlled failure tests were carried out after an edge cut had been made in the pure shear specimen. Sources of secondary failure, either at the free edge of the specimen, or due to the presence of inhomogeneities in the tissues, were common. Analysis of the test results suggested that the fracture surface energy of stratum corneum has a mean value of 3.6 kJ m-2 which is comparable with the tougher synthetic polymers.

Mouthpiece forces produced while playing the trumpet.

A transducer for measuring the force applied to the trumpet mouthpiece during performance is described. The device allowed the players to perform on their own instrument and in their usual manner. The results of tests on 60 subjects showed that during playing the force between the mouthpiece and instrument increased with increasing loudness and ascending pitch but that there was no significant correlation between mouthpiece force and proficiency or style. The maximum force which the players could tolerate was greater for high proficiency players than for medium.