[Telemedical prenotification in acute stroke treatment : Experiences from the Stroke Angel initiative from 2004 until the present]. / Telemedizinische Voranmeldung in der akuten Schlaganfallversorgung : Erfahrungen der Stroke-Angel-Initiative von 2004 bis heute.

OBJECTIVE: The Stroke Angel initiative investigates the implementation of telemedicine for improvement of preclinical communication between emergency medical services (EMS) and stroke units in cases of acute stroke. MATERIAL AND METHODS: Stroke Angel is a technical system for the telemedical prenotification of patients in cases of suspected stroke at a stroke unit by the EMS. Within the framework of an observational study, the team has been investigating the effects of the system on door-to-computed tomography (CT) and door-to-needle times as well as the lysis rate in the neighboring regions of Rhön-Grabfeld and Bad Kissingen since 2005. RESULTS: The system supports the acute treatment of neurological emergencies and functions as a catalyst for the interlinking of medical institutions in the region as well as for communication between emergency physicians/EMS and hospital physicians. The use of a computer-based data collection enables a continuous improvement process leading to an acceleration of internal clinical procedures and an increase of the lysis rate with the mortality rate staying constant. CONCLUSION: Telemedicine is applicable in the preclinical care of acute stroke and, thanks to the computer-based data collection, leads to an increase in process transparency, which helps to improve the internal clinical processes in and around a stroke unit.

A comparison study of amitriptyline and nortriptyline with plasma levels.

Forty-one depressed outpatients were treated for six weeks after random assignment to amitriptyline hydrochloride (N = 22) or nortriptyline hydrochloride (N = 19). On a mean daily dose of 119 mg, amitriptyline-treated patients had a mean tricyclic level (amitriptyline plus nortriptyline) of 120 ng/ml. Nortriptyline-treated patients on a mean dose of 117 mg/day had a mean nortriptyline level of 141 ng/ml. The two drugs were equally effective in the treatment of depression. The correlation between the Hamilton Score and the mean tricyclic level was negative in the amitriptyline-treated patients (r = -0.54, P less than .025) and positive in the nortriptyline-treated patients (r = -0.49, P less than .05). Patients treated with amitriptyline or nortriptyline with plasma levels within the therapeutic range, defined in other laboratories, had a better response, as measured by the Hamilton Score (P less than .001), Zung Score (P less than .01), and percent recovered (P less than .001), than those above or below the therapeutic range.

Sampling time, dosage schedule, and nortriptyline plasma levels.

Steady-state nortriptyline plasma levels were determined in eight patients at 9 AM, 12 PM, 3 PM, and 6 PM during treatment with nortriptyline hydrochloride administered as a single daily bedtime (hs) dose at 10 PM and repeated after changing the dosage schedule to three times a day (tid) with divided doses at 10 AM, 4 PM, and 10 PM. Overall, the mean levels were stable during the sampling period and comparable on the two schedules. As expected, the plasma level decreased at the later sampling times on the hs schedule and increased on the tid schedule. In seven of the eight patients, the differences on the two dosage schedules were less than 30 ng/ml, which is not considered clinically significant. One patient had a higher plasma nortriptyline level on the tid schedule, which was clinically significant. Standardization of sampling time is of importance when comparing plasma levels and therapeutic response in treatment studies.

Protriptyline plasma levels and antidepressant response.

Twenty-one depressed outpatients were treated for 4 wk with 20 mg/day of protriptyline. Protriptyline plasma in individuals after 4 wk ranged from 22 ng/ml to 167 ng/ml. There was a negative correlation (-0.50, less than 0.05) between the severity of depression measured by the Hamilton Rating Scale (HRS) and the wk 4 protriptyline concentration. Patients with plasma levels above 70 ng/ml (wk 4) had better outcomes measured by the HRS (p less than 0.05) and the Zung Self-Rating Depression Scale (p less than 0.05) and had greater percent decreases on both scales (p less than 0.05) during treatment than those with lower plasma levels. An upper limit to the therapeutic plasma level range beyond which response to treatment was less satisfactory was not demonstrated in this study.

Nortriptyline plasma levels and therapeutic response.

Eighteen depressed outpatients were treated for 6 wk with a mean daily dose of 121 mg of nortriptyline. The mean plasma level was 138 ng/ml during treatment. Therapeutic response was monitored by the Zung Self-Rating Depression Scale and the Hamilton Depression Scale administrered by two psychiatrists blind to the tricyclic used, dose, and plasma levels. Eight patients recovered (Hamilton less than or equal to 6) by the fourth week and 12 by the sixth week. During the steady-state (wk 4 to 6) there was a positive correlation between the weekly Hamilton scores and the weekly nortriptyline levels (p less than 0.01). The 9 patients with mean plasma levels between 50 and 139 ng/ml had a better therapeutic response after 6 wk measured by percent recovered (p less than 0.005). Zung score (p less than 0.05), and Hamilton score (p less than 0.025) than the 9 patients with mean plasma levels between 140 and 260 ng/ml.

Amitriptyline plasma levels and therapeutic response.

Eighteen depressed outpatients were treated for 6 wk with amitriptyline. Clinical improvement was monitored using the Hamilton Depression Rating Scale administered by two psychiatrists blind to the tricyclic used for treatment, dosage, and plasma levels. Amitriptyline and its desmethyl metabolite, notriptyline, were assayed twice weekly by gas chromatography-mass fragmentography. For the 17 patients having total tricyclic plasma levels between 0 and 250 ng/ml, there was a negative correlation between the Hamilton score and the mean total tricyclic level (p less than 0.01) and amitriptyline level (p less than 0.005). The mean nortriptyline level did not significantly correlate with the Hamilton score. The 10 patients having mean total tricyclic levels above 95 ng/ml had lower median Hamilton scores at week 3 (p less than 0.025) and at week 6 (p less than 0.0025) than those whose tricyclics were lower. The percentage of recovered patients increases significantly as the plasma levels rise to 250 ng/ml, the maximum plasma level considered in this study.

Doxepin kinetics.

The kinetics of doxepin (DOX) hydrochloride were studied in 7 volunteers after the oral administration of 75 mg. Peak plasma concentrations of DOX ranged from 8.8 to 45.8 ng/ml and were reached within 4 hr. The disappearance of DOX was biphasic and followed first-order kinetics. The mean DOX half life (t1/2) was 16.8 hr and in individuals ranged from 8.2 to 24.5 hr. The mean apparent volume of distribution was 20.2 L/kg and ranged from 9.1 to 33.3 L/kg. The estimated first-pass metabolism of DOX ranged from 55% to 87% of the oral dose assuming complete absorption. Significant quantities of the metabolite desmethyldoxepin (DMD) were produced. Peak levels of DMD ranged from 4.8 to 14.5 ng/ml and were reached between 2 and 10 hr after administration. The mean t1/2 of DMD was 51.3 hr and in individuals ranged from 33.2 to 80.7 hr. There was no correlation between the DOX and DMD t1/2s. The amount of DMD produced correlated with the plasma concentration of DOX and appears to explain the correlation between the steady-state concentrations of DOX and DMD in patients given DOX.

Protriptyline kinetics.

The kinetics of protriptyline were examined in 8 subjects after a single oral dose of 30 mg protriptyline hydrochloride. Peak protriptyline levels ranged from 10.4 to 22.3 ng/ml and were reached 6 to 12 hr after the oral dose. The mean protriptyline half-life (t1/2) was 74.3 hr and ranged from 53.6 to 91.7 hr in individual subjects, confirming the long t1/2 of protriptyline reported by Moody and associates. The estimated first-pass metabolism of protriptyline was relatively small, ranging from 10% to 25% of the oral dose, assuming complete absorption. The mean volume of distribution was 22.5 L/kg and ranged from 15.0 to 31.2 L/kg. No relationship was found between the kinetics of protriptyline and those of doxepin studied previously in 7 of the 8 subjects.

Tricyclic antidepressant plasma levels and adverse effects after overdose.

Forty patients ingesting tricyclic antidepressant (TAD) overdoses were studied as a pharmacologic model to determine whether total tricyclic antidepressant plasma levels correlated with major adverse effects and electrocardiographic findings. Maximum TAD plasma levels were higher in patients who died (p less than 0.025) or had cardiac arrest (p less than 0.02), needed respiratory support (p less than 0.005), were unconscious (p less than 0.02), had grand mal seizures (p less than 0.001), ventricular rate larger than or equal to 120/min (p less than 0.01), cardiac arrhythmia (p less than 0.05), QRS duration larger than or equal to 100 msec (p less than 0.001), or bundle branch block (p less than 0.05). TAD plasma levels correlated with the dose ingested by history (N = 29, r = 0.58, p less than 0.001). Measurement of total TAD (free and protein-bound) appears to correlate well with biologic response.

Immunological detection of cauliflower mosaic virus gene V protein produced in engineered bacteria or infected plants.

Antiserum was prepared against a synthetic peptide corresponding to the C-terminal 25 amino acids (aa) of the protein encoded by cauliflower mosaic virus (CaMV) gene V, which is thought to be a reverse transcriptase involved in viral DNA replication. This antiserum was used to detect the expression of CaMV gene V either in Escherichia coli JM103 transformed by an expression vector containing CaMV gene V or in CaMV-infected plants. In both cases, an 80-kDal protein has been detected.

Dosage schedule and plasma levels of doxepin and desmethyldoxepin.

Plasma levels of doxepin and its metabolite desmethyldoxepin were determined in 7 depressed patients treated with doxepin hydrochloride in 3 divided doses at 1000, 1600, and 2200 hours (t.i.d.), and repeated after changing the dosage schedule to a single daily bedtime (h.s.) dose at 2200 hours. Doxepin and its metabolite were measured at 9000, 1200, 1500, and 1800 hours. None of the individual patients showed clinically significant changes in their plasma concentration of tricyclic antidepressant on the 2 dosage schedules. No difference in the clinical condition of the patients was detected on the 2 dosage schedules using the Zung Self Rating Depression Scale, however patients experienced more morning sedation while on the single h.s. dosage. This study provides pharmacological support for the prescription of doxepin on a once daily basis.

Imipramine and desipramine plasma levels: relationship to dosage schedule and sampling time.

Tricyclic antidepressant plasma levels were determined after administration if imipramine (11 patients) and desipramine (ten patients) as a single daily bedtime dose or in divided doses. Plasma levels of the tricyclics were relatively stable on both dosage schedules due to the long plasma half-lives of these drugs. No difference was found between the two dosage schedules and the therapeutic effectiveness or the severity of side effects. The majority of patients preferred the single dose schedule. These findings support the use of a single daily dose of imipramine and desipramine.

Contribution to the pharmacokinetics of amitriptyline.

The clinical pharmacokinetics of amitriptyline were studied in four volunteers after the oral administration of 75 mg. Peak amitriptyline plasma concentrations ranged from 10.8 to 43.7 ng/ml. The disappearance was biphasic and followed first-order kinetics. The mean elimination half-life was 36.1 hours. The mean estimated first-pass metabolism of amitriptyline was 60 per cent. Significant quantities of the metabolite, nortriptyline, were produced although peak concentrations ranged from only 5.9 to 12.3 ng/ml. The relationship between these findings to clinical practice and earlier reports is discussed.

Brofaromine (CGP 11 305 A): estimation of plasma concentrations by a biologic technique as compared to liquid chromatography.

In an open clinical trial 13 depressives significantly improved under the reversible and selective type-A monoamine oxidase (MAO) inhibitor brofaromine. The inhibitory potency of deproteinated plasma on a crude MAO preparation from human placenta was measured as a parameter for plasma brofaromine. There were no significant differences in plasma MAO inhibitory potency between responders (improvement greater than 50%; n = 5) and non-responders. MAO inhibitory potency significantly (p less than 0.05) increased parallel to the increase of the dosage from 50 mg b.i.d. to t.i.d. confirming the validity of this technique. The biologic assay, however, overestimated brofaromine by a factor of two in acute kinetic experiments with healthy volunteers as compared to a chromatographic technique, although both methods significantly correlated (r = 0.928).

Symptoms as predictors of response to amitriptyline and nortriptyline -- the plasma level variable.

Data collected to define therapeutic plasma levels for amitriptyline and nortriptyline were re-analyzed to test endogenous and non-endogenous symptoms as response predictors while controlling for plasma level variable. The selection criteria limited the range of historical predictors. Initial symptom quality was not predictive of outcome for the entire group of 44 patients or for the 27 with therapeutic plasma levels. Delusions were not associated with poor outcome. The authors conclude that historical components of the endogenous--non-endogenous distinction (e.g., premorbid personality, stability of symptoms over time, quality of remissions) may be more important as response predictors.

Southeast Asian renal exchange list.

More than 340,000 Southeast Asians (SE Asians) have immigrated to the United States since 1971. By 1984, 76,000 SE Asians had settled in California. In areas of the U.S. with large SE Asian populations, many foods specific to those people are readily available. Approximately 5% of the total U.S. population has medical problems that lead to kidney disease. Many SE Asian refugees have prior medical problems, such as hepatitis B, that may make them at significantly higher risk for kidney disease. A modified renal exchange list (excluding milk, carbohydrate supplement, and fat group) was developed. This list, made up of foods readily available and commonly eaten by the largest group of SE Asian immigrants, the Vietnamese, categorizes foods by protein, potassium, and caloric content. A separate list, indicating the phosphorus content of these foods, is also included. Asian grocery stores were visited to identify foods available for purchase by SE Asians. The foods were identified, and nutrient composition was found in food composition tables. Because the Vietnamese diet is high in potassium and sodium, planning renal diets poses problems for both patients and dietitians. Close monitoring of diet can retard the progression of renal disease. An exchange list such as this assists both dietitians and renal patients in this important task.

Origin of the enhanced activity of lysosomal beta-galactosidase in serum and skin in progressive systemic sclerosis.

In 14 patients with progressive systemic sclerosis (PSS) the activities of acid lysosomal glycosidases (alpha-, beta-galactosidase, beta-glucosidase, beta-glucuronidase, and beta-N-acetyl-glucosaminidase) were determined fluorometrically in serum, leukocytes, and skin tissue. The beta-galactosidase was the only enzyme which exhibited a significantly elevated activity in PSS serum and skin but not leukocytes, as compared to the control. The activity patterns of the studied glycosidases in serum were similar to those found in skin, but differ from the distribution of glycosidase activities in leukocytes. In cultured dermal fibroblasts derived from PSS patients, an elevated intracellular activity of beta-galactosidase was detected. These results suggest that the increased beta-galactosidase activity in the serum originates from the skin fibroblasts.

Intrapatient variability of serial steady-state plasma tricyclic antidepressant concentrations.

Nine or 10 serial steady-state plasma measurements of amitryptyline, desipramine, desmethyldoxepin, doxepin, imipramine, nortriptyline, or protriptyline were made in 23 depressed patients. Each patient was monitored for compliance by pill counts, and sampling time was controlled carefully to determine intrapatient variability of steady-state tricyclic levels on a day-to-day basis. The coefficients of variation during serial sampling of the various ingested drugs were: amitriptyline, 21%; desipramine, 26%; doxepin, 21%; imipramine, 14%; nortriptyline, 13%; and protriptyline, 17%. The therapeutic ranges for the tricyclic antidepressants are relatively wide, so coefficients of variation of these magnitudes indicate that the position of an individual patient in relation to the optimal therapeutic range can be reliably determined on a clinical basis.

[CT of the upper ankle joint. Anatomy--pathology]. / CT des oberen Sprunggelenkes. Anatomie--Pathologie.

Diagnosis of ligament ruptures via the possibilities of conventional radiology is often insufficient. To verify CT efficiency, postmortem specimens were scanned in axial, coronal and sagittal planes and compared with anatomical findings of sections in identical planes. After the preliminary examinations we conducted a study on 32 patients. The examinations of the anterior talofibular ligament showed a correlation between CT and operative findings in 30 of 32 cases.

[Contact eczema and "standard test"--do "International Standard Test Series" coincide with Austrian local characteristics?]. / Kontaktekzem und "Standardtest"--Entsprechen "Internationale Standardtestreihen" den österreichischen Gegebenheiten?

Testing with a "standard" group of substances has proved of great value when allergic contact dermatitis is suspected and the offending agent cannot be pinpointed by careful history-taking. But internationally standardized series do not take into account locally important and individual factors, changing consumer habits or economic aspects. We have, thus, compared the suitability of two standard series, the ICDRG-European and the DKG-German standard, for Austrian purposes. 1,478 patients with a clinical diagnosis of contact dermatitis were patch tested between 11/88 and 4/90 with the ICDRG allergens; the second collective of 505 patients was tested between 5/90 and 1/91 with the DKG series. Only 12 out of the 27 substances of the ICDRG series exceeded the critical incidence of 1%; 6 were below this limit but positive in more than 0.5% and 9 hardly ever aroused positive reactions. In the DKG series, 17 out of 23 substances surpassed the limit, 2 were positive in more than 0.5%, and 4 caused virtually no reactions. However, 4 allergens with frequent sensitization rates were included neither in the ICDRG nor in the DKG series and 2 others were missing in the over-dimensioned ICDRG standard. Our results demonstrate that internationally established standard series have to adapted for the local situation in Austria, and that a constant review is essential with replacement of allergens as necessary according to changing production techniques and consumer habits. Suggestions for an "Austrian standard patch test series" are proposed on the basis of our results but in spite of being helpful in general terms interpretation of such a test in the individual patient with eczema remains problematic.