Driving in Parkinson's disease - a health hazard?

BACKGROUND: The driving safety of Parkinson's disease (PD) patients has lately been questioned after several authors reported road accidents caused by sleep attacks in PD patients on dopaminergic medication. OBJECTIVES: To determine 1) whether PD patients in general and those on dopaminergic medication in particular are especially prone to cause severe road accidents and 2) whether there are PD symptoms or dopaminergic side effects with the potential to compromise driving safety. DATA SOURCE: Relevant articles were identified by electronic search of biomedical databases (1966-2002: MEDLINE, EMBASE, PASCAL, PUBMED), the Cochrane Controlled Trials Register, and reference lists of located articles. RESULTS: Despite frequent occurrence of potentially hazardous dopaminergic side effects (2-57 %) and disabling parkinsonian non-motor and motor disabilities (16-63 %), the two existing studies on accident rates suggest that PD patients are not more prone to cause road accidents than the rest of the population. Five further reports including 1346 patients and focusing on dopaminergically induced sleep attacks provided comparably low accident figures (yearly incidence: 0%-2%). Because of low figures meta-analysis was intended but finally deemed inappropriate as the methodology of included studies varied greatly and was frequently flawed. CONCLUSION: Further prospective community-based well designed studies on accident risk in PD patients are needed to provide evidence based driving recommendations.

Influence of age, gender, education and dexterity on upper limb motor performance in Parkinsonian patients and healthy controls.

Finger tapping, the most widely used test for evaluating motor dysfunction in Parkinson's disease (PD), was found to react sensitively to disease specific factors like disease severity and changes in medication. A possible interference caused by disease unrelated demographic factors--age, gender, education and dexterity--however has not yet been studied systematically. Various components of tapping performance of 187 healthy subjects and 200 PD patients were assessed by means of the BRAIN TEST, a digitalized test battery. The effects of demographic factors--above all education and age--were found to be significant. These influences generally affect different aspects of movement to a different extent, with speed and akinesia being affected more severely than dysmetria and arrhythmokinesis. Our study suggests that whenever precise assement of upper limb motor performance is needed, specific corrections for these demographic factors in both healthy controls and PD patients are necessary.

East-west differences in the organization of botulinum toxin use in nine Central European countries.

Availability and quality of expensive treatment modalities such as botulinum toxin (BTX) largely depend on organizational aspects such as costs, reimbursement by insurance companies, expertise and facilities for expert training, and the propagation of research. To investigate which determinants influence the organization of BTX' use throughout nine Central European countries (Austria, Croatia, Czech Republic, Germany, Hungary, Italy, Slovakia, Slovenia and Switzerland) we sent out questionnaires to leading BTX experts and consulted data banks of manufacturers and bulletins of international organizations. In Western European countries, there is a tendency for users to organize themselves in formal groups and to concentrate on research whereas the way how BTX is provided is diverse regarding qualifications of specialists and institutions. In the post-communist Eastern European countries, we found a tendency towards a centralized system of reimbursement and BTX treatment seems to be more in the hands of neurologists than any other specialists. Strong correlations were observed between the number of BTX centres, degree of organization of user groups and number of scientific publications, on the one hand, and parameters of healthcare performance and socioeconomic determinants, on the other. Our study suggests that in the nine countries surveyed, organizational aspects of BTX use vary considerably, whilst similarities are based mainly on socioeconomic rather than socio-demographic determinants.

Agraphia as the only symptom of migraine aura: a case report.

A 37-year-old female migraine patient is described, who suffered from episodes with pure lexical agraphia as the only symptom of migraine aura. The MRI showed multiple subcortical white matter lesions. Central inflammatory and demyelinating disorders were excluded. This case suggests that, during a migraine aura, even very circumscribed brain areas involved in complex neuro-psychological processing can be affected.

[Heparin dosage in long-term intravenous administration based on the example of vascular surgery patients]. / Heparindosierung bei intravenöser Dauerapplikation am Beispiel gefässchirurgischer Patienten.

For prophylaxis of deep-vein thrombosis, 23 male and 7 female patients received intravenous 15 000 IE/24 h sodium-heparin continuously after different operations for blood-vessel surgery. The plasma heparin concentration was measured with chromogenic substrate at 0, 1, 2, 4, 8 and 12-18 hours after beginning of heparin application. Each patient's hematocrit, sex, height, weight and parameters of liver and renal function were measured at the same time. The aim of this investigation was to find a general model for intravenous heparin application which would allow the best individual therapeutic plasma heparin concentration to be obtained. At the latest eight hours after the beginning of heparin-infusion the steady state of plasma heparin concentration was reached in 100%, but only in 56.67% it equalled the therapeutical factor Xa inhibition-level of 0.10 IE/ml to 0.20 IE/ml (= 0.077 USP-E/ml to 0.154 USP-E/ml). It was found that the plasma heparin concentration correlates negatively with the plasma volume. The heparin halftime depends on the dosage. Plasma heparin concentrations from 0.04 IE/ml to 0.20 IE/ml (= 0.031 USP-E/ml to 0.154 USP-E/ml) correlate to heparin halftimes of 9 min to 38 min. With this results formulae for calculating the quantity of the bolus and the daily heparin application were obtained. As opposed to the liver function the kidney function does not have any significant effect on the plasma concentration of biological active heparin. Furthermore it was found that the actual weight is unreliable for determination of the dosage. Instead calculated weight (height minus 100) is to be used.

[Dosage and possibilities for controlling thrombosis prevention with low-dose heparin]. / Dosierungs- und Kontrollmöglichkeiten der Thromboseprophylaxe mit low-dose Heparin.

The dosage of subcutaneous heparin examined (2 X 7500 international units per day) was shown to be unsatisfactory, as the average plasma heparin level in the patients was too low for over 9 h/day. This was a result of the fact that the interval between doses was too long and the therapy regimen thus not quite right. It was not possible to adjust the dose according to body height and weight because of lack of correlation with the plasma heparin levels. Control of the dose effect by the thrombin-clotting time test only showed a weak correlation. For high-risk patients in particular, an individually adjusted dosage is mandatory. Determination of the plasma heparin level can be helpful.

[Acute right bronchial blockade following intubation with a left-swing Robertshaw tube]. / Akute Bronchialblockade rechts nach Intubation mit dem linksschwingenden Robertshaw-Tubus.

After proper insertion of an intact leftsided Robertshaw endotracheal tube an acute block of the right main bronchus occurred in two patients. The cause was seen in too short a distance between the upper tracheal and the lower bronchial cuff of the tube. In case of a greater distance between the cuff-bearing segments this problem was never encountered. A careful measurement of all Robertshaw tubes demonstrated segments of various length between the upper and lower cuffs. Information from the manufacturer Malinckrodt New York/Grossostheim revealed that this problem has been solved by standardized segments of greater length. Also the Portex company Hythe/Hamburg appears to be aware of this problem.

[The modified Kleinsasser tube: the ideal in difficult intubation]. / Das modifizierte Kleinsasser-Rohr: Ideal für die schwierige Intubation.

The modified Kleinsasser tube is commonly used for laryngeal tumour diagnosis. The tube has a semilunar cross-section with a radius of 2.5 cm and a diameter of 3 cm. Its lower third contains a cold light lamp placed so that it cannot become covered by blood or tumour masses. After insertion of the endotracheal tube into the patient the Kleinsasser tube is placed at the entrance of the larynx. Operations are done through the inner lumen of the Kleinsasser tube. The Kleinsasser tube has proved a reliable instrument for insertion of endotracheal tubes in patients whose vocal cords could not be seen by ordinary laryngoscopy, e.g. patients with a short neck and unable to recline, with severe hypopharyngeal haemorrhage, with obstruction at the base of the tongue and partial occlusion of the laryngeal entrance by tumour. After introduction the vocal cords may be inspected in their entire length and under bright light the endotracheal tube may be brought safely through the Kleinsasser tube into endotracheal position using Magill forceps as an auxiliary instrument.

[Effect of anesthesia on blood coagulation factor XIII]. / Zum Einfluss der Narkose auf den Blutgerinnungsfaktor XIII.

57 patients who had undergone surgical operations because of varicosis were examined for the influence of the mode of anaesthesia on the plasma levels of factor XIII. Within a randomized study the patients were given by alternate order halothane (NA) (n = 19), neurolept-analgesia (NLA) (n = 19) or peridural anesthesia (PA) (n = 19). Pre- and postoperatively as well as at the 1st, 3rd, 5th, and 7th p.o. day the plasma levels of factor XIII, fibrinogen (factor I) and fibrinogen-degradation-products (FDP) were measured. FDP were not found. The levels of factor XIII remained within the normal range. Fibrinogen showed an identical course: the postoperative findings were lower than the initial ones. 24 h later the levels were higher. At the 7th p.o. day the most important readings were found. In comparing the three methods of anaesthesia the most obvious differences in the data on factor XIII were in the peridural anesthesia-group, especially on the 3rd p.o. day with significant lower results than in the other groups. The modes of anaesthesia used had no visible influence on the range of factor XIII.

Tumor cells carried through autotransfusion. Are these cells still malignant?

A suspension of 3 X 10(7) cells of longterm carcinoma cell lines--HLaC 78 and 79 from human laryngeal carcinoma, CaKi 1 derived from renal cell carcinoma and PC 3 from prostatic carcinoma,--was pumped with maximum pressure up to 5 times through the filters of the Bentley autotransfusion device. Following filter passage after centrifugation the untrapped cells were recovered, counted and brought in culture under appropriate conditions. As soon as monolayers were obtained 3 X 10(6) cells were transferred subcutaneously into athymic mice. The time intervals of growth in culture and of developing tumor nodules in nude mice were measured. The histological pattern of the daughter tumors in nude mice was compared with the genuine tumor. After the first filter passage 12.3% respectively 18.2% untrapped cells were found. This number dropped to 3% after the 5th passage. After the 5th passage in only 3 out of 5 experiments there were enough cells to start a culture. After the first passage cell proliferation in the culture as well as yielding tumor nodules in nude mice was markedly reduced. HLaC78 died. After the 5th passage cell growth in the culture as well as tumor growth in nude mice was reduced the more while using HLaC79. Taking CaKi 1 and PC 3 both parameters showed identical growth behaviour as compared with the original not-filter-passaged cells. The histological findings were identical with the pattern of the genuine tumors.

[Autotransfusion with the Sörensen apparatus]. / Zur Autotransfusion mit dem Sörensen-Gerät.

Since 1980 in Würzburg the Sorensen autotransfusion unit has been clinically used in 47 patients (35 vascular, 11 trauma patients, one with arterial bleeding after BII, one with aneurysm of the a. pericallosa) and tested to study its practicability, its advantages and disadvantages. Within the laboratory data there was a small decrease of hemoglobin, hematocrit and blood platelets, as well as of the "Quick" and AT-3. PTT and thrombin-time persisted unchanged, as did the results of electrolytes, parameters of renal and liver function, and the status of blood gas analysis. Free hemoglobin i.s. or i.u. was found in three patients with extremely high volume autotransfusions. The autotransfusion unit is convenient, easy to use and reliable. However, it is only suitable for the reinfusion of blood when hemorrhage is moderate and not severe. Hemothorax blood can be used only when adequate anti-fibrinolytic therapy is guaranteed. Nevertheless, the use of the Sorensen autotransfusion unit within the named diagnoses can achieve a precious contribution for saving homologous blood.

[Donor nephrectomy]. / Zur Spendernephrektomie.

Using 76 protocols of anaesthesia for donor nephrectomy from 1976 to 1982, the early selection of a possible cadaver kidney-donor and the requirements for donation are reported as well as measures of ascertaining cerebral death, possibilities to obtain the consent for donation and the course and organization of donor nephrectomy. Own experiences show that cadaver nephrectomy can be carried out without any disturbance of the routine operative program. The task of the anaesthesiologist is not specific but related to the fundamental knowledge of his specialty. Amelioration of the organization and the operative technique (in situ perfusion) shorten the amount of time, medicaments and infusions to be administered by all cooperating medical and paramedical personnel.

[Mechanical intraoperative autotransfusion]. / Maschinelle intraoperative Autotransfusion.

The cardiac effects during maximum pressure autotransfusion of blood which was anticoagulated by different methods, were studied in 2 series of 9 dogs. The animals, which were anaesthetized and splenectomized, received each 300 i.v. heparin/kg bodyweight intravenously before being subjected to repeated maximum pressure auto-transfusions of 10% of their whole blood volume. The anticoagulant employed during each autotransfusion was changed in station as follows: Heparin-(ACD-B)-Citrate-Heparin-CPD-Citrate... and so on. Criteria of cardiac efficiency, signs of insufficiency, pumpfunction (force of contraction, contractility) were all derived from the 4 phases of the aortic pressure tracing. In addition various parameters of the ECG, using the "Colletti distances", were measured. The results were proved by laboratory data. Immediately after the pre-determined bleeding (V) there was a characteristic fall of all parameters corresponding to the acute reduction in circulating blood volume, which returned to normal after the autotransfusion was completed (G). During the transitory phase S all data remained stable when heparin had been employed as the anticoagulant. Following the use of citrate, however, particularly CPD, there was an ensuing fall in all accounted for by the acute withdrawal of Ca++ which could be measured. Subsequently the circulation stabilized (ST) spontaneously and all parameters being measured returned to their original values when heparin and ACD-B had been used. With CPD, however, the force of contraction, enddiastolic pressures and propagation of electric activity of the heart were still altered.

[The QT-interval during "pressure-autotransfusion" with heparin and citrate (author's transl)]. / Das QT-Intervall unter der "Druckautotransfusion" mit Heparin und Citrat.

Nine anaesthetized, splenectomized dogs, heparinized with 300 IU/kg heparin i.v. had one tenth of their blood volume returned to them by autotransfusion under pressure. The blood was mixed with 1:5 0,9% NaCl for the "Heparin-Autotransfusion", and with 1:5 ACD-B or CPD-stabilisor for the "Citrate-Autotransfusion". The blood was removed from an opening made in the left renal artery, and autotransfused with the Bentley-System. A Stathem-Element was used to monitor the aortic pressure and the tracing obtained was divided into four phases: V is at the end of the blood loss before autotransfusion, G is at the peak, S is at the trough and ST is at the phase when the aortic pressure becomes stable. In these four phases the heart rate was also measured in the normal way using needle electrodes in the extremities. Following the method of Colletti the QT intervals of the ECG (RR, QoTc, QTc, SaTc, SoTc) were measured. Immediately after the blood loss (phase V) we found no alteration in the heart rate, depolarisation, isoelectric phase or repolarisation of myocardium. In phase G during the increase in blood volume, the heart rate slowed slightly, but the QT interval was unchanged. In the following phase S, during Heparin-Autotransfusion the heart rate was slightly reduced whilst the ECG remained unchanged. During Citrate-Autotransfusion there was a reduction in heart rate, and a corresponding prolongation of the QTc and QoTc, significantly, without any relationship to the infused dose of citrate. The prolongation of the SaTc and especially of the SoTc correlated directly with the infused dose of citrate. In phase ST using CPD only SaTc and SoTc were prolonged.

[Changes in the pump function of the right ventricle during "pressure-autotransfusion" with citrate and heparin (author's transl)]. / Anderung der Pumpfunktion des rechten Ventrikels unter der "Druckautotransfusion" mit Citrat und Heparin.

Nine anaesthetized, splenectomized dogs, heparinized with 300 IU/kg bodyweight heparin i.v. had one tenth of their total blood volume returned to them by autotransfusion under maximum pressure with the Bentley-system. For the "Heparin"-autotransfusion (n = 49) 1:5 0,9% NaCl was added to the blood; whilst for the "Citrate"-autotransfusion 1:5 ACD-B(n = 28) or CPD (n = 30) stabilisor was added. Autotransfusion was performed as follows: Heparin-ACD-B- Heparin-DPD- Heparin-ACD-B etc. The pump function of the right ventricular myocardium was measured by the force of contraction (PRV, IP, SV, T1) as well as by criteria of contractility (dp/dtmax, VCEmax, KI1, KI2). Immediately after acute bleeding a reduction of the force of contraction to 50% was seen, but the contractility remained unchanged. During the maximum pressure autotransfusion of the blood the force of contraction consistently increased irrespective of the anticoagulant used. The contractility remained unchanged. In the following phase the force of contraction and the contractility normalised when heparin was employed, whilst when citrate was used there was a reduction of the force of contraction and of the contractility corresponding with the different dose of citrate of ACD-B and CPD. This short phase was followed by spontaneous stabilisation of the circulation. The force of contraction and the contractility returned to normal when heparin and ACD-B were employed, whilst a reduction of these criteria occurred when CPD was used. From these findings, the scheme of anticoagulation for citrate under clinical conditions should be modified by a prior injection of 2,000-3,000 IE of heparin i.v. and the addition of citrate in the ratio of 1:7 for ACD-B or 1:8 for CPD.

[Changes in ionized calcium and citrate levels in dogs during mechanical autotransfusion with heparin, ACD and CPD]. / Veränderungen des ionisierten Calciums und des Zitratspiegels beim Hund während maschineller Autotransfusion mit Heparin, ACD und CPD.

The control of ionized calcium (Ca++), total calcium, and citrate levels in serum were determined in dogs during autotransfusion (AT) of blood stabilized with heparin, ACD (formula B) and CPD. Blood samples were taken according to the changes of aortic pressure (AOP), which was continuously monitored. Taking the values during the stable phase of AOP preceding the AT as baseline, Ca++ dropped by 27% with ACD and by 34% with CPD at the maximum decrease of AOP immediately after the AT. The corresponding increase of citrate was 174% with ACD and 521% with CPD, while total calcium remained stable. Thus cardiac depression after AT of citrated blood seems to be mainly caused by the drop of Ca++, which is significantly more pronounced with CPD, corresponding to the higher content of citrate.

[The influence of intraoperative autotransfusion (IAT) on plasmaproteins in patients with posttraumatic intraabdominal bleeding or hemorrhage during vascular surgery (author's transl)]. / Plasmaproteine unter dem Einfluss maschineller intraoperativer Autotransfusion (IAT) bei gefässchirurgischer und traumatischer intraabdomineller Blutung.

In 29 patients (12 vascular and 17 trauma cases) the effect of intraabdominal bleeding and surgical management under intraoperative autotransfusion on several plasmaproteins was examined. The following parameters were monitored immediately before and after autotransfusion as well as 24, 48, 72 hours and one week later, in the thawed serum: 1. albumen and the carrier proteins prealbumen, transferrin, retinol-binding protein, 2. acute phase reactants: c-reactive protein coeruloplasmin, haptoglobin, 3. fractions of complement: C1q, C3c, C5 and C 3-activator, 4. serum-cholinesterase. With usual treatment by infusion of electrolyte solutions during operation and the following days, and further applicated blood transfusion, plasma and fresh frozen plasma by clinical needs, while the immediate blood loss during operation was replaced by autotransfusion, there was no change in preoperative dates. Only at the 3rd day the typical picture of catabolic situation of the postoperative period was observed in vascular cases and not at all in trauma cases. Thus the changes were closely related to the preexisting disease or state of shock, without further detoriation by intraoperative autotransfusion. 7 days later a sometimes overshooting normalization of the parameters was observed. Only cholinesterase remained extremely low, especially in vascular cases.

[The effect of citrate or heparin coagulation on the dog's heart work in autotransfusion]. / Der Einfluss von Citrat- oder Heparinanticoagulation bei der Autotransfusion auf die Herzarbeit des Hundes.

During massive autotransfusion in the dog, the different anticoagulation processes have an important influence on heart work and performance. This is especially marked with citrate, depending on the amount and the transfusion rate. In spite of normovolemia both parameters show a transient decrease up to 40% - 50% with ACD and up to 60% - 70% with CPD. These different reactions may be due to the corresponding composition of each stabilizer. The effect is abolished by simultaneous use of citrate and calcium, which may prove that the observed changes are caused mainly by a depletion of ionized calcium caused by the rapid transfusion. This is comparable to the well-known citrate intoxication. In contrast both cardiac parameters decrease only about 10% with heparin anticoagulation. Heparinization seems to be preferable to citrate as regards heart work and performance during massive autotransfusion. Also the two citrate stabilizers significantly differ in their effect on both cardiac parameters, the use of ACD being favoured.

[Intraoperative autotransfusion, technical management and its influence on blood circulation, on kidney and electrolytes (author's transl)]. / Erste Erfahrungen mit der maschinellen intraoperativen Autotransfusion. Technik und Einfluss auf Kreislauf, Niere und Elektrolyte.

From February 1975 until July 1976 12 patients who elective surgery and 15 trauma victims received intraoperative autotransfusion. The effects of this method on these patients were controlled by monitoring the behaviour of circulation and of important laboratory parameters. The procedure was well tolerated: 1. Only three of 29 patients showed evidence of cardiac insufficiency (lowering of ST. elevated T-peak, low blood pressure, high central venous pressure) which disappeared after reducing the rate of infusion. --2. Blood pressure, pulse rate and central venous pressure were stable at the end of the operation. --3. There was no renal insufficiency under dopamine (210 microgram/min) and 15% manitol (250 ml i.v.). --4. Serum creatine showed only minor changes from the initial level during the time of observation. --5. The same was true for beta2-microglobulin. --6. Serum urea rose slightly during 7 days. --7. There were minor changes of electrolytes without hypocalcaemia or high potassium. --8. The observed changes showed no relation to the method of anticoagulation and to time or volume of autotransfusion.