Association of increased plantar pressures with peripheral sensorimotor and peripheral autonomic neuropathy in Type 2 diabetic patients.

AIM: Diabetic polyneuropathy plays a highly significant role in the pathogenesis of the diabetic foot syndrome. It was the objective of this study to investigate the association of different forms of neuropathy (cardiac autonomic, sensorimotor and peripheral autonomic) with elevated plantar pressures in diabetic patients. METHODS: A total of 103 Type 2 diabetic patients was investigated. High plantar pressure was diagnosed when the total peak pressure was greater than 500 N/m2. Thirty-three participants were identified as patients with high-risk pressure and 70 patients had a mean peak pressure lower than 500 N/m2. All patients underwent a complete medical examination including determination of neuropathy, vascular status and foot pressures. RESULTS: Peripheral sensomotoric (p<0.012) and peripheral autonomic neuropathy (p<0.05) were significantly found more often in patients with high plantar pressures. There was no apparent association between autonomic cardial neuropathy and enhanced foot pressure (p=0.175). CONCLUSIONS: Our data clearly point to a correlation of diabetic neuropathy and higher plantar pressures. Interestingly, while there was a strong association between peripheral measures of neuropathy, no higher incidence of cardiac neuropathy in patients with increased foot pressure profiles was found. We strongly recommend that patients with clinical signs and indices of peripheral neuropathy be monitored by pedobarography for early detection and prophylactic shoe care for preventing the development of a diabetic foot ulcer.

Effects of preventative footwear on foot pressure as determined by pedobarography in diabetic patients: a prospective study.

AIMS: This study analysed the effects of specially manufactured insoles on foot pressures in diabetic patients during a 1-year prospective observation period. METHODS: We studied 81 type 2 diabetic patients without foot lesions. Using pedobarography three different regions of interest were examined: maximum peak pressure (MPP) of the total foot area, heel region and head of metatarsal bone I-III. Eighteen patients with high risk pressure (MPP of total foot 474 +/- 183 kPa; heel region 278 +/- 147 kPa, metatarsal 389 +/- 222 kPa) received optimal insole support. Sixty-three patients as a control group (MMP of total foot 367.7 +/- 157 kPa; heel 263.1 +/- 127 kPa, metatarsal 339.9 +/- 171 kPa) received conventional footwear. RESULTS: After insole support a 30% pressure reduction of total foot MMP (474 +/- 183 kPa vs. 290 +/- 106 kPa) was achieved in the treatment group. After 6 months (324 +/- 127 kPa) and 1 year (380 +/- 190 kPa) a pressure reduction was found. Between the 6- and 12-month controls plantar pressures again increased. In the control group a significant increase of all peak pressures occurred. CONCLUSIONS: Early insole support is successful in reducing plantar pressure. A repeated adjustment should be performed every 6 months to prevent foot pressure increases. The comparison of foot pressure development between the two groups showed constant levels in the treatment group. In the control group a marked increase of the pressure values was found. Identification and subsequent support of patients with high ulceration risk may help to reduce the high amputation rate.

Induction of DNA double-strand breaks in mammalian cells and yeast.

Induction of DNA double-strand breaks (dsb) and their distribution are dependent on the energy deposition pattern within the cell nucleus (physical structure) and the ultrastructure of the chromosomes and its variation by the cell cycle and gene activities (biological structure). For electron radiation very similar RBE-values are observed for mammalian and yeast cells (AlK, 1.5 keV, 15 keV/micrometer: 2.6 in mammalian cells and 2.2 in yeast; CK 0.278 keV, 23 keV/micrometer: approx. 2.5 in mammalian cells and 3.8 in yeast). In contrast, the RBE-values for the induction of dsb of 4He2+ and light ions in the LET range from about 100 keV/micrometer up to 1000 keV/micrometer are significantly higher for yeast cells compared to mammalian cells. For example, the RBE-value of alpha-particles (120 keV/micrometer) is about 1.2 for mammalian cells whereas for yeast the RBE-value is about 2.5. The yeast chromatin has less condensed fibres compared with mammalian cells. Since a single CK photoelectron can induce only one dsb, the different condensation of the mammalian and yeast chromatin has no influence. However, particles may induce more than one dsb when traversing a chromatin fibre. The probability for the induction of closely neighboured dsb is higher the more condensed the chromatin fibres are. Since small DNA fragments (50 bp up to several kbp) are lost by standard methods of lysis, the underestimation of dsb yields increases with fibre condensation, which is in accordance with the observes dsb yields in mammalian cells and yeast. In order to obtain relevant yields of dsb (and corresponding RBE-values) the measurement of all DNA fragments down to about 50 bp are needed.

Induction of DNA double-strand breaks by 1H and 4He lons in primary human skin fibroblasts in the LET range of 8 to 124 keV/microm.

Yields of DNA double-strand breaks were determined in primary human skin fibroblasts exposed to 1H and 4He ions at various linear energy transfers (LETs) and to 15 MeV electrons as the reference radiation. The values obtained for the relative biological effectiveness (RBE) were 2.03, 1.45 and 1.36 for 1H ions at LETs of 35, 23 and 7.9 keV/microm, respectively, and 1.2, 1.18, 1.38 and 1.31 for 4He ions at LETs of 124, 76, 35 and 27 keV/microm, respectively. The data were obtained using pulsed-field gel electrophoresis of DNA released from cells using the chromosomes of the yeast Saccharomyces cerevisiae as length markers and fitting the experimental mass distributions of fragmented DNA to those obtained by computer simulation of the random breakage of human chromosomes. The RBE values for induction of DSBs in mammalian cells cannot be fitted to a common RBE-LET relationship for electrons and 1H, 4He and light ions. Comparison of the RBEs for mammalian cells with the corresponding RBEs obtained for yeast cells shows similar RBEs of electrons for yeast and mammalian cells; however, for 4He and light ions in the LET range of 100 to 1000 keV/microm, the RBEs for yeast are significantly higher compared with mammalian cells. These characteristics of the RBE-LET relationships for yeast and mammalian cells are attributed to the fraction of small DNA fragments induced by particles when traversing the higher-order chromatin structures which are different to some extent in these two cell types.

[Measurement of depth dose curves of soft x-rays in a water phantom]. / Messung von Tiefendosiskurven weicher Röntgenstrahlen im Wasserphantom.

A device is described which allows to perform dosimetry with a usual flat chamber made of plexiglas (PTW soft ray chamber) in the water phantom. The depth dose curves measured for anode potentials of 10 to 100 kV were compared to the curves measured a) in a plexiglas phantom, b) in a M3 phantom using a soft ray chamber made of M3, c) in a mixed phantom consisting of a plexiglas bottom, a soft ray chamber made of plexiglas flush with its surface, and plates or foils made of M3, polystyrene, and frapan. The results show that there is no difference between the depth dose curves measured in water and those measured in the homogeneous M3 phantom if the curve is plotted over the mass related to the surface (g/cm2). There is also no difference to the dose curve measured in the mixed phantom according to c) if M3 plates determining the depth of measurement are layed on it. With the other substances, considerable deviations are found. An example is presented in order to warn against the uncontrolled use of "plastic foils" as phantom material for soft ray depth dose curves.

Comparison of resuscitation of sheep and dogs after bupivacaine-induced cardiovascular collapse.

This study evaluated interspecies sensitivity and ability to resuscitate pentobarbital anesthetized sheep and dogs after cardiovascular toxic doses of bupivacaine. Every minute, 3 mg/kg of bupivacaine was injected into the right atrium over the course of 10 sec until cardiovascular collapse occurred. While the bupivacaine was given, the animals were made apneic for 90 sec and then ventilated with 100% oxygen. After the bupivacaine administration, cardiovascular collapse occurred in the form of electromechanical dissociation progressing to asystole in dogs, whereas in sheep the predominant rhythm was ventricular fibrillation leading to asystole. Resuscitation was performed using open chest heart massage, bretylium for treatment of ventricular tachycardia and fibrillation, and epinephrine with atropine for treatment of electromechanical dissociation or asystole. The initial dose of bupivacaine used to cause cardiovascular collapse was 3.5 +/- 1.2 mg/kg in sheep and 24.6 +/- 8.5 mg/kg in dogs (P less than 0.01). All sheep and dogs were resuscitated from the first cardiovascular collapse. The resuscitation time was 2.1 +/- 1.0 min in dogs and 36.9 +/- 15.4 min in sheep (P less than 0.01). All dogs could be resuscitated after two additional cardiovascular collapses induced by bupivacaine, but no sheep could be resuscitated after a second cardiovascular collapse. Concentrations of bupivacaine in cardiac tissue and serum levels of bupivacaine after the last resuscitation attempt were significantly greater in the dogs than in the sheep. We conclude that sheep are more sensitive to bupivacaine than dogs, but that even sheep can be resuscitated after cardiovascular collapse produced by bupivacaine.

Amide local anesthetic alterations of effective refractory period temporal dispersion: relationship to ventricular arrhythmias.

The hemodynamic and electrophysiologic effects of bupivacaine, etidocaine, mepivacaine, and lidocaine were investigated in 32 pentobarbital-anesthetized adult mongrel dogs. Following equipotent dosing, all four agents produced similar hemodynamic effects: decrease in stroke volume and cardiac output, heart rate slowing, increase in systemic vascular resistance, and increases in pulmonary arterial pressure (PAP) and pulmonary capillary wedge pressure (PCWP). The effects of the various agents on the ECG were different. Compared with the control period, mepivacaine and lidocaine produced slight increases and etidocaine and bupivacaine much greater increases in: the area under the curve of the T-wave; lengthening of the QTU interval; and enhancement of the "slow wave" or U-wave following the T-wave. The effects of the various agents on effective refractory period (ERP) temporal dispersion were dramatically different. The ERP temporal dispersion increased to 48.3 +/- 36.0 ms following mepivacaine, 37.4 +/- 10.1 ms following lidocaine, 97.1 +/- 36.2 ms following bupivacaine, and 92.5 +/- 30.5 ms following etidocaine. Six of seven bupivacaine, six of seven etidocaine, two of eight mepivacaine, and none of eight lidocaine animals sustained a polymorphic, undulating ventricular tachycardia similar to Torsades de Pointes following burst ventricular pacing. The results of this study suggest that bupivacaine, etidocaine, and occasionally mepivacaine can result in a Torsades de Pointes-like syndrome following intravenous administration. The magnitude of ERP temporal dispersion differences between the various agents appears to explain their differential arrhythmogenicity.

Evaluation of lidocaine as an adjunct to fentanyl anesthesia for coronary artery bypass graft surgery.

A double-blind, randomized, prospective trial was conducted to evaluate intravenous lidocaine, 3 mg/kg, followed by an infusion of 0.05 mg X kg-1 X min-1, as an adjunct to fentanyl in 20 patients undergoing coronary artery bypass graft surgery. Lidocaine prevented hemodynamic abnormalities during tracheal intubation and after skin incision, but was ineffective in preventing hypertension following sternotomy. Intravenous lidocaine, 3 mg/kg, produced a decrease in mean arterial pressure after fentanyl, 30 micrograms/kg, that was unacceptable in some patients. Total fentanyl requirements for the duration of surgery were similar in the control group and in patients given lidocaine. We conclude that lidocaine, when administered as an adjunct to fentanyl in the dosage used in this study, can cause cardiovascular depression, and is of minimal benefit in preventing hemodynamic abnormalities after sternotomy during coronary artery bypass graft surgery.

Resuscitation from bupivacaine-induced cardiovascular toxicity during partial inferior vena cava occlusion.

The hemodynamic effects and ability to resuscitate animals experiencing bupivacaine cardiovascular toxicity after partial inferior vena cava occlusion were investigated in anesthetized dogs (n = 12). Partial occlusion of the inferior vena cava resulted in a 12% decrease in mean arterial pressure, a 62% decrease in cardiac output, a 66% decrease in stroke volume, and a 135% increase in systemic vascular resistance. Bupivacaine, 20 mg/kg intravenously, resulted in cardiovascular collapse in all animals. The resuscitation time for animals without partial caval occlusion was 2.1 +/- 0.5 min, whereas that for animals with partial caval occlusion was 22.2 +/- 6.9 min (P less than 0.05). Significantly increased amounts of epinephrine and NaHCO3 were required to resuscitate the animals with caval occlusion. We conclude that partial inferior vena cava occlusion can significantly alter the ability to resuscitate animals experiencing bupivacaine cardiovascular toxicity.

Bupivacaine cardiovascular toxicity: comparison of treatment with bretylium and lidocaine.

Using anesthetized dogs, this study compared treatment with lidocaine or bretylium for bupivacaine-induced cardiovascular toxicity. Pentobarbital-anesthetized and -ventilated dogs (n = 10) were given a bolus dose of bupivacaine, 4 mg/kg, and a constant infusion of 0.2 mg X kg-1 X min-1 to produce steady-state serum levels of 7.1 +/- 1.8 microgram/ml of bupivacaine. Using burst ventricular pacing, the ventricular tachycardia threshold was determined, along with hemodynamic and electrophysiologic parameters. The animals were then treated with bretylium, 20 mg/kg (n = 5), or lidocaine, 2 mg/kg, followed by a continuous infusion of lidocaine, 0.1 mg X kg-1 X min-1 (n = 5). Bupivacaine-induced alterations in cardiac output, stroke volume, heart rate, and systemic vascular resistance were corrected by bretylium but not lidocaine. Bupivacaine caused a significant lowering of the ventricular tachycardia threshold, which was consistently raised by bretylium, while lidocaine was either ineffective or caused a further lowering of the threshold. Bupivacaine caused a significant increase in the Q-TU interval and resulted in an undulating polymorphic ventricular tachycardia, similar to that seen in Torsades de Pointes.

Successful cardiovascular resuscitation after massive intravenous bupivacaine overdosage in anesthetized dogs.

We investigated whether anesthetized dogs (n = 6) could be resuscitated from massive cardiovascular toxic intravenous bupivacaine overdoses. Five mg/kg of bupivacaine was given into the right atrium over 10 sec every minute until cardiac collapse occurred. At the same time the bupivacaine was given, the animals were made apneic for 90 sec (to mimic the clinical situation in which seizures often render patients apneic) and then ventilated with 100% oxygen. After bupivacaine administration, cardiovascular collapse occurred in the form of ventricular tachycardia, or more commonly, electromechanical dissociation. Resuscitation was performed using open-chest heart massage, bretylium for ventricular tachycardia, and epinephrine with atropine for electromechanical dissociation and bradycardia. After successful resuscitation, each animal was again given bupivacaine as above until cardiovascular collapse occurred and resuscitation was performed again. Each dog underwent three arrests and resuscitations. The total cumulative bupivacaine dose was 64.1 +/- 26.8 mg/kg. We conclude that anesthetized dogs receiving massive cardiovascular toxic doses of bupivacaine can be resuscitated easily and consistently with appropriate therapy.

[Concept of the mean stopping power and the mean electron energy in electron dosimetry]. / Zum Konzept des mittleren Bremsvermögens und der mittleren Elektronenenergie in der Elektronendosimetrie.

In consideration of the variations of the values E,Er,EH and Ew of the energy spectrum of electrons at the measuring point in case of a given energy on the surface Eo and in the depth t of a phantom with a low Z-number, the authors present the practical realisation of a conception allowing to determine by one single conversion curve Sw,1 (Er) the energy-dose of rapid electrons in water Dw, at least within the spectrum of Eo = 5 to 42 MeV and Er = 2.2 to 42 MeV, from the cavity ion dose Jc measured absolutely or by means of a calibrated electron chamber. Sw,1 (Er) is the relative unrestricted mass collision stopping power as a function of the mean rest energy Er at the measuring point. Er can be calculated in a simple manner from Eo and t and coincides almost perfectly with the most probable energy Ew of measured electron spectra. The authors present an algorithm for the calculation of the true mean electron energy E from Eo and t with a good coincidence with the values of measured electron spectra. It is shown that, contrary to the curve with one parameter Sw,1 (Er), a relation of Sw,1 to E leads to a series of curves with two parameters Sw,1 (Eo, t). The method using a relation of Sw,1 to Er which offers the advantage of a simple practical application and good precision is presented as "conception of the mean stopping power in electron dosimetry".

[Absolute ionization dosimetry of high energy electrons with an energy of more than 15 Mev]. / Absolute Ionisationsdosimetrie schneller Elektronen oberhalf von 15 MeV.

By means of a graphite double extrapolation chamber, the self consistent dosimetry system already used for an electron energy until 15 MeV also allows an absolute determination of the cavity ion dose until 42 MeV which can be performed under practically ideal Bragg-Gray conditions with the precision of a primary standard. For the conversion into energy-dose, the relative mass collision stopping power sw,l reduced to the universal dosimetric constants W/e, G and epsilon is used which is determined by the system itself and corresponds to the theoretic relative unrestricted mass collision stopping power. A clear function for sw,l only depending on Er is achieved by a co-ordination with the mean rest energy of electrons Er, and that in any measuring depth. This function also harmonizes with the theoretical values of the relative unrestricted mass collision stopping power in the enlarged energy range. The performance specifications and influence quantities of the small parallel-plate chamber ("Electron Chamber") which also has been already used until 15 MeV as a secondary standard dosemeter and field instrument in the water, M3 or plexiglas phantom keep the same values and ranges of use. The calibration factor of the cavity ion dose is independent of the energy and remains constant also for the enlarged energy range. The measuring accuracy for the cavity ion dose and the energy-dose are unchanged.