Die Wirkung länger dauernder Hydrochlorothiazid-Gaben auf die Plasma-Renin-Aktivität und die Aldosteron-Exkretionsrate bei Normalpersonen

Zusammenfassung Die Wirkung von Hydrochlorothiazid auf die Plasma-Renin-Aktivität (PRA) und die Aldosteron-Exkretionsrate (AER) wird bei 10 Normalpersonen untersucht. Gleichzeitig werden Bestimmungen der Serum- und Urinelektrolyte, des Hämatokrits und der Flüssigkeitsbilanz durchgeführt. In derjenigen Gruppe, die während 7 Tagen täglich 50 mg Hydrochlorothiazid (Esidrex®) erhielt, steigen die PRA am 2. und 4. Tag und die AER am 3. Tag nach Beginn der Diuretikagabe signifikant an, während am 6. bzw. am 7. Tag ein Abfall beider Parameter zur Norm einsetzt. Wesentliche Änderungen der Serumelektrolyte und des Hämatokrits werden nicht registriert. Die Stimulation des Renin-Angiotensin-Aldosteron-Systems (RAAS) kann mit einer erhöhten Natriurese und Diurese korreliert werden. Die Kaliurese steigt ebenfalls deutlich an, so daß der Na/K-Quotient im Urin unter 1 abfällt.In derjenigen Gruppe, die während 6 Wochen täglich 50 mg Hydrochlorothiazid erhielt, werden nach 2, 4 und 6 Wochen der Diuretikaverabreichung keine signifikanten Veränderungen der PRA, AER, Serumelektrolyte und des Hämatokrits festgestellt. Es entwickelt sich demnach unter längerdauernden Saluretikagaben kein sekundärer Hyperaldosteronismus.Die Wirkung sowohl einer Natriumrestriktion als auch einer saluretikainduzierten Natriumexkretion auf das RAAS wird besprochen. Schließlich werden die Möglichkeiten diskutiert, die einen Rückgang der Stimulation des RAAS trotz andauernder Diuretikagaben bewirken können.

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Summary The effect of hydrochlorothiazide on plasma renin activity (PRA) and aldosterone excretion rate (AER) were examined in 10 normal persons. At the same time, determinations of serum and urine electrolytes, of hematocrit and of fluid balance were carried out. In that group which recieved 50 mg hydrochlorothiazide (Esidrex®) daily for 7 days, the PRA rose significantly on the 2nd and 4th day and the AER on the 3rd day after the beginning of diuretic treatment. A decline to normal in both parameters set in on the 6th and 7th day, respectively. Considerable changes in serum electrolytes and hematocrit were not registered. The stimulation of the renin-angiotensin-aldosterone system (RAAS) could be correlated with elevated natriuresis and diuresis. Kaliuresis rose considerably as well so that the Na/K quotient in urine fell under 1.In that group which recieved 50 mg hydrochlorothiazide daily for a period of 6 weeks, no significant changes were noticed in PRA, AER, serum electrolytes or hematocrit after 2, 4 and 6 weeks of diuretic treatment. There was no development of secondary hyperaldosteronism under extended saluretic treatment.The effect of sodium restriction as well as saluretica-induced sodium excretion on the RAAS is discussed. Finally, the possibilities are discussed which can cause a retreat in stimulation of the RAAS despite extended treatment with diuretics.

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Diese Arbeit wurde durch die Hilfe des Schweizerischen Nationalfonds zur Förderung der wissenschaftlichen Forschung und der Stiftung zur wissenschaftlichen Forschung an der Universität Zürich ermöglicht.     

Bestimmung der Plasma-Renin-Konzentration mittels Radioimmunoassays für Angiotensin I

Zusammenfassung Ein Radioimmunoassay für Angiotensin I und seine Anwendung für die Messung der Reninkonzentration im Plasma werden beschrieben. Die zur Herstellung von Angiotensinantikörpern und radioaktiv markiertem Angiotensin sowie zur Trennung von gebundenem und freiem Hormon benutzten Verfahren werden mitgeteilt. Die Empfindlichkeit der Methode erlaubt den Nachweis von zwanzig Pikogramm Angiotensin I.Zur Messung der Reninkonzentration wurde substratfreies Plasma mit Schafsubstrat im Überschuß versetzt und in Anwesenheit von Inhibitoren von converting enzyme und Angiotensinasen bei 37°C inkubiert. Das gebildete Angiotensin wurde in 20 µl des proteinfreien Inkubationsgemisches bestimmt. Die initiale Geschwindigkeit der Angiotensinbildung wurde zur Berechnung der Reninkonzentration herangezogen. Als eine Einheit wurde die Reninmenge definiert, die ein Nanogramm Angiotensin I pro Stunde Inkubation bildet.Normalwerte unter kontrollierter natriumreicher und natriumarmer Diät wurden ermittelt.Die Empfindlichkeit der Methode erlaubt die Messung der Reninkonzentration im Plasma von Patienten mit primärem Aldosteronismus.Mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Captopril in Cushing's syndrome

Summary To analyse the role of the renin angiotensin system in the pathogenesis of hypertension in Cushing's syndrome ten patients with hypercorticism (five with pituitary hypothalamic dysfunction, three with adrenal adenomas and two with adrenal carcinomas) received a single oral dose of 25 mg captopril. Mean arterial pressure was then determined at short intervals over periods of up to 240 min. Plasma renin activity (PRA) was measured immediately before the administration of captopril. Eleven patients with severe essential hypertension, who showed a comparable distribution of basal PRA values, served as a control. Patients with elevated basal PRA values (>3 ng/ml·3 h) showed, both in the subgroup of cases with essential hypertension and in that with Cushing's syndrome, a statistically significant fall (P<0.05–P<0.001) in mean arterial pressure, the decrease being slightly more pronounced in essential hypertensives. On the other hand patients with normal PRA values (3 ng/ml·3 h) exhibited only a minor fall in mean arterial pressure reaching statistical significance (P<0.05) only after 60 min (essential hypertension) and 180 min (Cushing's syndrome), respectively. Our results document that in patients with Cushing's syndrome the effect of captopril seems to be determined by the activity of the renin angiotensin system. Thus, in a substantial number of patients with hypercorticism, the renin angiotensin system may be an important factor in the pathogenesis of hypertension, whereas in patients with low PRA values other factors like oversecretion of mineralocorticoids may be responsible for the observed blood pressure increases.     

Intensity modulated proton therapy: a clinical example

In this paper, we report on the clinical application of fully automated three-dimensional intensity modulated proton therapy, as applied to a 34-year-old patient presenting with a thoracic chordoma. Due to the anatomically challenging position of the lesion, a three-field technique was adopted in which fields incident through the lungs and heart, as well as beams directed directly at the spinal cord, could be avoided. A homogeneous target dose and sparing of the spinal cord was achieved through field patching and computer optimization of the 3D fluence of each field. Sensitivity of the resultant plan to delivery and calculational errors was determined through both the assessment of the potential effects of range and patient setup errors, and by the application of Monte Carlo dose calculation methods. Ionization chamber profile measurements and 2D dosimetry using a scintillator/CCD camera arrangement were performed to verify the calculated fields in water. Modeling of a 10% overshoot of proton range showed that the maximum dose to the spinal cord remained unchanged, but setup error analysis showed that dose homogeneity in the target volume could be sensitive to offsets in the AP direction. No significant difference between the MC and analytic dose calculations was found and the measured dosimetry for all fields was accurate to 3% for all measured points. Over the course of the treatment, a setup accuracy of +/-4 mm (2 s.d.) could be achieved, with a mean offset in the AP direction of 0.1 mm. Inhalation/exhalation CT scans indicated that organ motion in the region of the target volume was negligible. We conclude that 3D IMPT plans can be applied clinically and safely without modification to our existing delivery system. However, analysis of the calculated intensity matrices should be performed to assess the practicality, or otherwise, of the plan.     

Renovaskuläre Hypertonie

Zusammenfassung In der vorliegenden Untersuchung wurde das postoperative Blutdruckverhalten bei 35 Patienten mit renovaskulärer Hypertonie untersucht: 17 Patienten mit fibromuskulärer Dysplasie (FMD) und 18 mit arteriosklerotischen Gefäßwandveränderungen (ASS).Patienten mit FMD waren im Mittel jünger (31,8 Jahre), zeigten eine kürzere Hypertonieanamnese (1,8 Jahre) und waren prävalent weiblich (82%), während Patienten mit ASS deutlich älter waren (48,2 Jahre), eine längere Hypertoniedauer (2,6 Jahre) zeigten und bevorzugt männlich (78%) waren.In beiden Gruppen zeigte das intravenöse Pyelogramm einen vergleichbar hohen Anteil positiver Befunde (FMD=64%, ASS=61%).Postoperativ waren in der Gruppe mit FMD 47% (n=8) geheilt, 47% (n=8) gebessert und nur 6% (n=1) der Patienten geringgradig gebessert. Die vergleichbaren Werte für die Gruppe mit ASS betrugen 28, 55 und 17%. Für das Gesamtkollektiv war folglich ein guter Operationserfolg (geheilt und gebessert) in 88,5% der Fälle zu beobachten. Patienten mit ASS und postoperativ nur geringgradiger Besserung (n=3) zeigten eine auffallend lange Hypertonieanamnese (7,0±1,4 Jahre).Bei allen Patienten wurde präoperativ die seitengetrennte Bestimmung der Renin-Aktivität (PRA) im Nierenvenenblut durchgeführt und aus den Werten die PRA-Quotienten (PRA betroffene/nicht betroffene Seite) errechnet. Bei 27 Patienten wurde die Bestimmung 15 und 30 min nach intravenöser Stimulation mit 40 mg Furosemid wiederholt. PRA-Quotienten von 1,5 wurden als signifikant bezeichnet.Bei 31 Patienten mit einseitiger renovaskulärer Hypertonie wurde die Höhe des PRA-Quotienten zum postoperativen Blutdruckverhalten korreliert. Dabei zeigte sich zwischen der Gruppe der postoperativ Geheilten und der der postoperativ Gebesserten kein signifikanter Unterschied im mittleren PRA-Quotienten. Ferner ließen sich für das Gesamtkollektiv der 31 Patienten mit einseitiger renovaskulärer Hypertonie unter Ausgangs- und Stimulationsbedingungen keine signifikanten Korrelationen zwischen Höhe der PRA-Quotienten und postoperativem Blutdruckabfall ermitteln.Unsere Ergebnisse unterstützen nicht die weit verbreitete Ansicht, daß sich die seitengetrennte Bestimmung der PRA im Nierenvenenblut als Parameter für den zu erwartenden Operationserfolg bei Patienten mit einseitiger renovaskulärer Hypertonie eignet. Die Methode kann deshalb nach unserer Ansicht nicht mehr als obligater Bestandteile der präoperativen Diagnostik der renovaskulären Hypertonie empfohlen werden.     

Long-term experience in percutaneous transluminal dilatation of renal artery stenosis

Percutaneous transluminal dilatation was attempted in 65 patients with renovascular hypertension. In five cases (8 percent), percutaneous transluminal dilatation could not be performed for technical reasons. In the remaining 60 patients (35 with atherosclerotic stenosis and 25 with fibromuscular dysplasia), both mean systolic and diastolic pressure fell immediately after percutaneous transluminal dilatation and remained significantly lower for a period of up to five years. Cure rates after a mean control period of 21.6 months were higher in patients with fibromuscular dysplasia (50 percent) than in those with atherosclerotic stenosis (29 percent). Improvement of blood pressure was observed in 32 percent of patients with fibromuscular dysplasia and in 48 percent of patients with atherosclerotic stenosis. Follow-up angiography in 33 cases showed occlusion of the dilated artery in two patients and recurrence of slight renal artery stenosis in nine patients. Successful redilatation could be performed in five of these cases. Furthermore, renal vein renin determinations were only of limited diagnostic or prognostic value. These results document the good long-term effect of percutaneous transluminal dilatation in patients with renal artery stenosis. Percutaneous transluminal dilatation should, therefore, be the favored procedure in patients with renovascular hypertension.     

Gastrointestinal involvement in acquired immunologic deficiency syndrome (AIDS)

The gastrointestinal tract is a major target organ of the acquired immunodeficiency syndrome. Opportunistic infections or Kaposi's sarcoma within the gastrointestinal tract are the two most frequent lesions. Diarrhoea, weight loss or odynophagy may be the presenting symptoms or signs for which a gastroenterological consultation is sought. In this report we present our own observations of patients with AIDS. Diagnostic and therapeutic aspects of this new syndrome are discussed.     

Stabbing energy and force required for pocket-knives to pierce ribs

Purpose

In addition to reconstructing the course of events, the medical examiner will often have to answer questions regarding the force necessary to inflict a certain injury in stabbing incidents. Several groups have examined the force needed to penetrate soft-tissue and clothing; however, no studies addressing the energy needed for penetrating ribs exist. Therefore, we decided to investigate this force on an animal model.

Method

Ribs from healthy, 8 to 10-month-old pigs were used as a substitute for human ribs. These ribs were then stabbed either transversely or longitudinally with two different pocket-knife blades, namely a Swiss Army pocket knife and a sturdier pocket knife (Classic Schnitzmesser, Herbertz Solingen) dropped from a drop-tower at defined heights and therefore defined energies.

Results

Longitudinally orientated stabs showed complete piercing of the ribs at approximately 11 Joules (J) or with a stabbing force in excess of 906 Newton (N) for both blade types. Transversely orientated stabs, however, displayed complete piercing between 11 and 16 J, or in excess of 1198 N, with the sturdy pocket knife tending to require a little more energy than the Swiss army pocket knife.

Conclusions

Young adult porcine ribs are completely pierced by pocket knife blades at energies between 11 and 16 J. Assuming the porcine ribs are comparable to those ribs of young adult humans, our results indicate that a complete penetration of the chest wall through the ribs by stabbing with a pocket knife is rather easily achieved.

     

Task difficulty in mental arithmetic affects microsaccadic rates and magnitudes

Microsaccades are involuntary, small‐magnitude saccadic eye movements that occur during attempted visual fixation. Recent research has found that attention can modulate microsaccade dynamics, but few studies have addressed the effects of task difficulty on microsaccade parameters, and those have obtained contradictory results. Further, no study to date has investigated the influence of task difficulty on microsaccade production during the performance of non‐visual tasks. Thus, the effects of task difficulty on microsaccades, isolated from sensory modality, remain unclear. Here we investigated the effects of task difficulty on microsaccades during the performance of a non‐visual, mental arithmetic task with two levels of complexity. We found that microsaccade rates decreased and microsaccade magnitudes increased with increased task difficulty. We propose that changes in microsaccade rates and magnitudes with task difficulty are mediated by the effects of varying attentional inputs on the rostral superior colliculus activity map.     

Comparative study of NMP‐preloaded and dip‐loaded membranes for guided bone regeneration of rabbit cranial defects

Guided bone regeneration (GBR) has been utilized for several decades for the healing of cranio‐maxillofacial bone defects and, particularly in the dental field, by creating space with a barrier membrane to exclude soft tissue and encourage bone growth in the membrane‐protected volume. Although the first membranes were non‐resorbable, a new generation of GBR membranes aims to biodegrade and provide bioactivity for better overall results. The Inion GTR? poly(lactide‐co‐glycolide) (PLGA) membrane is not only resorbable but also bioactive, since it includes N‐methylpyrrolidone (NMP), which has been shown to promote bone regeneration. In this study, the effects of loading different amounts of NMP onto the membrane through chemical vapour deposition or dipping have been explored. In vitro release demonstrated that lower levels of NMP led to lower NMP concentrations and slower release, based on total NMP loaded in the membrane. The dipped membrane released almost all of the NMP within 15 min, leading to a high NMP concentration. For the in vivo studies in rabbits, 6 mm calvarial defects were created and left untreated or covered with an ePTFE membrane or PLGA membranes dipped in, or preloaded with, NMP. Evaluation of the bony regeneration revealed that the barrier membranes improved bony healing and that a decrease in NMP content improved the performance. Overall, we have demonstrated the potential of these PLGA membranes with a more favourable NMP release profile and the significance of exploring the effect of NMP on these PLGA membranes with regard to bone ingrowth. Copyright © 2014 John Wiley & Sons, Ltd.