Pyrazolopyrimidinediones are selective agents for Helicobacter pylori that suppress growth through inhibition of glutamate racemase (MurI).

Pyrazolopyrimidinediones are a novel series of compounds that inhibit growth of Helicobacter pylori specifically. Using a variety of methods, advanced analogues were shown to suppress the growth of H. pylori through the inhibition of glutamate racemase, an essential enzyme in peptidoglycan biosynthesis. The high degree of selectivity of the series for H. pylori makes these compounds attractive candidates for novel H. pylori-selective therapy.

Somatosensory-evoked potentials during carotid artery surgery: experience in 400 operations.

A prospective study was undertaken to determine the efficacy of monitoring somatosensory-evoked potentials (SEP) during carotid artery surgery in predicting a new ischemic neurologic deficit. Three hundred seventy-six patients underwent 400 reconstructions of the internal carotid artery. The mortality rate of the entire series was 0.8%. In 383 procedures, SEP amplitudes were always present during cross-clamping of the internal carotid artery. In spite of that, three neurologic deficits occurred, but all were associated with technical failures and not related to clamping ischemia. Complete loss of SEP amplitudes was noted in 17 procedures. Five of seven patients without an indwelling shunt showed a neurologic deficit after surgery, whereas shunt insertion in 10 resulted in three neurologic deficits. It is concluded that at present SEP recording is an accurate monitoring method in detecting clamping-related cerebral ischemia during carotid artery surgery.

Paranasal sinusitis associated with nasotracheal and orotracheal long-term intubation.

The impact of nasotracheal and orotracheal long-term intubation on the development of sinusitis paranasalis was investigated in a prospective study. Daily A-scan ultrasound examinations of the maxillary sinuses were performed on 44 intensive care unit patients (20 nasally, 24 orally intubated) who required prolonged intubation (greater than 24 hours). At the end of the investigation period 19 (95%) of 20 nasotracheally and 15 (63%) of 24 orotracheally intubated patients showed pathologic antral sinus findings. In nasally intubated patients the incidence of bilateral sinusitis was significantly higher and its onset sooner. Pathologic organisms were found in the sinus aspirates in seven of 13 nasotracheally intubated patients, but only in two of nine patients with an oral tube. Thus, the nasotracheal tube can be seen as an adding factor in the development of sinusitis paranasalis.

[Possibilities and limitations of intravenous anesthesia]. / Möglichkeiten und Grenzen der intravenösen Anästhesie.

The increasing importance of intravenous anaesthesia is based on two developments, namely the synthesis of substances capable of acting selectively and over the short term, and which are rapidly eliminated (good control), and a desire on the part of the anaesthetist to have an anaesthetic whose actions can be controlled in various ways. Efforts in this area are aimed at ensuring not only a minimum of stressing of organs by the anaesthetic, but also a minimisation of risks during the intra-operative phase, and a non-problematic maximally pleasant post-operative course. There are two problems that militate against the realization of these objectives. Although the substances presented here ideally permit the realization of some of these aims, at the same time they are associated with side effects that prevent their use from ever being completely non-problematical, and which should always prompt the exercise of particular care when employing these medications. In addition, the differentiable control made possible by the use of these drugs is (partly) offset by inadequate monitoring with respect to the qualities of the anaesthetic--a fact that modifies the potential advantages of intravenous anaesthesia.

Mepivacaine plasma levels after retrobulbar anesthesia.

Plasma concentrations of mepivacaine were determined after retrobulbar anesthesia. The measured maximal blood levels that can produce systemic side effects range from 1.23 to 4.88 micrograms/ml. We therefore recommend preoperative and intraoperative monitoring of arterial blood pressure and ECG.

[Ability to cough following large upper abdominal and thoracoabdominal interventions]. / Hustenfähigkeit nach grossen Oberbauch- und thorakoabdominalen Eingriffen.

In 40 patients who underwent large abdominal or thoraco-abdominal operations, the efficacy of intentional coughing was determined by recording the peak expiratory flow rate (PEFR) of two consecutive coughs. The measurements were made preoperatively and then 1, 2, 24, and 36 hrs. postoperatively. They consisted of two series, the first one completely uninfluenced, the second one following detailed instruction and manual assistance by the therapist. Before instruction, PEFR of the first cough averaged 5070 ml/s. and statistically significantly increased to 7100 ml/s. after instruction. The postoperative values decreased to about 30% of those found preoperatively. It was not before the first postoperative day that the values began to improve to above 40%. In all instances, the absolute PEFR-values of the first cough were significantly higher by 16 to 60% than those of the second one. From the results it is concluded that, after abdominal or thoraco-abdominal surgery, continuous instruction and assistance by the personnel are crucial for the efficacy of coughing.

[Sinusitis in long-term intubated, intensive care patients: nasal versus oral intubation]. / Sinusitis bei langzeitintubierten Intensivpatienten: Nasale versus orale Intubation.

UNLABELLED: Discussion of paranasal sinusitis as a nosocomial infection in the mechanically ventilated intensive care (ICU) patient has recently been intensified. Some authors have emphasized nasotracheal intubation as a possible pathogenetic pathway. The aim of this study was to investigate the impact of nasotracheal or orotracheal intubation on the development of sinusitis in ICU patients. METHODS: In a prospective study, we followed 44 patients who required mechanical ventilation (greater than 24 h) in the ICU because of prolonged recovery from abdominal, thoracic, or posttraumatic surgery. Twenty patients were intubated nasotracheally and 24 orotracheally. Assignment to the groups was random. All were provided with a nasogastric tube and initially treated with systemic antibiotics. They received local antimicrobial prophylaxis of the nose, oropharynx, and stomach. Daily a-scan examinations of the maxillary sinuses were performed from the day of admission to the ICU until extubation, tracheotomy, death, or transfer. The average observation period was 6.9 days in the oral group and 7.1 days in the nasal group. In the case of a pathologic finding, aspiration of the antral sinus was carried out. In this study sinusitis indicated a sonographic finding; it did not necessarily imply a bacterial infection. RESULTS: At the beginning of the observation period, 6 patients in the oral group and 4 in the nasal group already had a pathologic maxillary sinus finding. At the end, in 15 of 24 in the oral group and 19 of 20 in the nasal group unilateral or bilateral sinusitis could be demonstrated. Development of bilateral sinusitis (13/20 in the nasotracheal group, 8/24 in the orotracheal group) was mainly observed after the appearance of unilateral sinusitis. The site corresponded to the site of the nasal tube in 65%. Unilateral paranasal infection was observed in nasotracheally and orotracheally intubated patients after an average of 2.8 and 2.6 days, respectively, whereas bilateral sinusitis had an average time delay of 4.5 and 5.7 days. Aspiration of the maxillary sinus was performed in 22 of 34 cases with sinusitis. Pathogenic organisms could be demonstrated in 7 of 13 nasotracheally intubated patients but only 2 of 9 with orotracheal tubes. CONCLUSION: We found that patients intubated orotracheally developed significantly less sinusitis than those intubated nasotracheally. Edema, local infection of the nasal mucosa, or mechanical obstruction of sinus drainage pathways by the tube are possible explanations. The fact that 63% of orally intubated patients had a pathologic maxillary sinus finding as well suggests that in addition to other reasons, an increased central venous pressure, positive pressure ventilation, and the supine position must be regarded as predisposing factors that increase the incidence of sinusitis. We conclude that the conditions of critically ill patients predispose to the development of sinusitis. Nasotracheal intubation is to be regarded as an additional risk, and therefore oral intubation should be preferred.

[The effect of halothane, enflurane and isoflurane on resistance and compliance in patients with asthma or chronic obstructive lung diseases]. / Die Wirkung von Halothan, Enfluran und Isofluran auf Resistance und Compliance bei Patienten mit Asthma oder chronisch-obstruktiven Lungenerkrankungen.

In order to test the hypothesis that halothane is more effective and safer than enflurane and isoflurane in patients with reactive airway disease, a clinical trial was performed to compare these three agents in patients with asthma or chronic obstructive pulmonary disease (COPD). METHODS. After obtaining institutional approval and informed consent, 31 patients with bronchial asthma or COPD were studied (FEV1 less than 65% of FVC); all patients underwent extensive surgery of the paranasal sinuses. Premedication consisted of i.m. atropine and promethazine; anesthesia was induced with diazepam, fentanyl, etomidate, and succinylcholine and maintained with pancuronium and 50% N2O in O2 together with one of the volatile agents, halothane, enflurane, or isoflurane, selected at random. Patients were mechanically ventilated. On the basis of respiratory pressures, volumes, and flows, inspiratory (Rin) and expiratory (Rex) resistance and compliance (C) were calculated after induction (control), 15 min after the addition of the volatile agent (1.25 MAC), every 15 min during the surgical procedure, and at the end of the operation. RESULTS. In 1 case, airway resistance increased markedly a few minutes after administration of isoflurane. The results obtained in this patient were not included in the evaluation of the data. There were no statistically significant differences in the preoperative data or control values of Rin, Rex, and C among the three groups (n = 10 each). With the respective inhalational agents, Rin increased maximally between 3% (halothane) or 8% (enflurane) and 21% (isoflurane), Rex between 16% (halothane, enflurane) and 29% (isoflurane). For the most part, however, these changes were not statistically significant as compared with controls. Intergroup comparisons failed to reveal any statistically significant differences either. In all groups C decreased continuously to about 90% of control. DISCUSSION. The results show that in patients with asthma or COPD, airway resistance remains virtually unchanged during surgery and anesthesia under halothane or enflurane anesthesia. With isoflurane, however, the resistance may rise by a slight but not statistically significant extent. Furthermore, marked bronchospastic reactions occurred in 2 patients in the isoflurane group. Thus, the three volatile anesthetics studied were not found to be unequivocally safe and effective in preventing increases in bronchomotor tone. However, pharmacodynamic effects other than those on respiration (e.g., cardiovascular actions, arrhythmogenic threshold, metabolism, toxicity) must additionally be taken into consideration.

[Somatosensory evoked potentials in carotid surgery]. / Somatosensorisch evozierte Potentiale in der Karotischirurgie.

During carotid surgery a monitoring device that will identify patients with inadequate cerebral perfusion and impending cerebral damage after carotid clamping is desirable. Such patients may benefit from cerebral protective measures, which should be applied selectively as their use can also lead to complications. METHODS. In order to evaluate the reliability of somatosensory evoked responses as a means of detecting patients with insufficient collateral perfusion after carotid cross clamping, a prospective study involving 482 operations for reconstruction of supraaortic vessels was performed. Somatosensory evoked potentials (SEPs) were recorded from a cervical (C2-Fz) and a parietal (C3'/C4'-Fz) electrode above the ipsilateral hemisphere following stimulation of the contralateral median nerve. RESULTS. In 22 procedures (4.6%) complete flattening of the cortical SEP occurred after carotid cross clamping. In 7 of 9 cases in which no indwelling shunt was used despite electrical silence neurological deficits were found postoperatively. The SEP amplitude was restored in 12 of the remaining 13 patients with complete loss of the SEP after shunt insertion. Only 3 of these patients demonstrated neurological impairment. During 460 operations evoked potentials were always present. Nevertheless, 5 neurological sequelae were noticed despite unchanged SEP after carotid artery clamping. All deficits, however, were caused by embolization and were unrelated to reduced blood flow after carotid cross clamping. CONCLUSIONS. Our results confirm the reliability of SEP monitoring for the detection of significant cerebral ischemia after carotid clamping. In absence of the cortical SEP immediate shunt placement is necessary to avoid neurological deficits. On the other hand, the risks attendant on indiscriminate cerebral support (embolism after shunt placement, cardiac ischemia due to induced hypertension) can be avoided in the presence of cortical potentials. This allows protection of the heart and the brain by anesthetic management and enables the surgeon to perform endarterectomy with no hurry, to avoid technical failure. SEP data may also be helpful in decision making on reoperation to look for sources of embolization. In conclusion, advanced monitoring by somatosensory evoked responses may help to improve the outcome of carotid surgery.

[Need for standardized pain therapy in pediatric oncology patients]. / Zur Notwendigkeit einer standardisierten Schmerztherapie bei pädiatrisch-onkologischen Patienten.

Pain-management in pediatric-oncological patients is an interdisciplinary task. The working group pain--therapy of GPO tries to work up an analgesic concept for this group of patients. Pre-existing experience in the therapy with sustained release Morphine and Metamizol should be considered. The documentation-system is just worked up, we ask all pediatric oncological groups to cooperate.

Pharmacokinetics and pharmacodynamics of ketamine enantiomers in surgical patients using a stereoselective analytical method.

In a randomized, double-blind study, we have examined the stereoselective disposition and pharmacodynamic characteristics of ketamine in surgical patients after i.v. administration of S(+)-ketamine 1 mg/kg body weight (25 patients) or racemic ketamine 2 mg/kg body weight (25 patients). S(+)-Ketamine was not inverted to R(-)-ketamine. After racemate administration we observed statistically significant (P < 0.01) smaller clearance and volume of distribution for R(-)-ketamine compared with S(+)-ketamine. In contrast, the pharmacokinetic variables of S(+)-ketamine were not significantly different between treatment groups. Systolic and diastolic arterial pressure and heart rate increased significantly (P < 0.005) in both groups. At 1, 3 and 15 min after S(+)-ketamine administration, significantly greater increase in systolic and diastolic pressures were observed compared with the racemate group. There was no correlation between the changes in haemodynamic variables and plasma catecholamine concentrations, which remained unaffected after administration of the medications.

[Effect of isoflurane on respiratory mechanics]. / Der Einfluss von Isofluran auf die Atemmechanik.

The effects of the inhalational anaesthetic, isoflurane, on two major parameters of respiratory mechanics--resistance and compliance--were studied in a total of 30 patients. With increasing inspiratory concentrations of isoflurane, resistance was measured in 5 spontaneously breathing patients using the oscillation method. In 16 mechanically ventilated patients resistance and compliance were calculated from airway pressure, gas flow, and tidal volume. In 9 patients with asthma or COPD the course of resistance and compliance was recorded intraoperatively. An increase in resistance of up to 117% of the initial volume occurred during spontaneous respiration, and was caused by a decrease in tidal volume. During mechanical ventilation with constant tidal volume, no definite changes in resistance or compliance were seen with increasing isoflurane concentrations. In the patients with elevated airway resistance there were only minor, statistically non-significant changes in resistance and compliance. The results show that the effects of isoflurane on respiratory mechanics do not differ from those of halothane or enflurane. Therefore, isoflurane may be considered appropriate for use in patients with impaired airway resistance.

[Dosage-problems in controlled sodium nitroprusside hypotension in oto-rhino-laryngological surgery (author's transl)]. / Dosisprobleme mit Natriumnitroprussid bei kontrollierter Hypotension in der Hals-, Nasen- und Ohrenchirurgie.

During a study of 130 patients undergoing hypotensive anaesthesia for oto-rhino-laryngological surgery the most important dose problems with sodium nitroprusside (S.N.P.) were characterized. In 14% of the cases more than 15 mcg/kg body weight/min S.N.P. were required. Our data show, that the smallest S.N.P. consumption occurs during neuroleptanalgesia in combination with 0.3--0.8 Vol-% enflurane. On the other hand, during neuroleptanalgesia alone, in several cases toxic amounts of S.N.P. would have been necessary to produce adequate hypotension. In such cases about 0.5 mg/kg body weight dihydralazine must be employed as a supporting agent for hypotension. The influence of this drug on the manoeuvrability of the low pressure state and on the administration of S.N.P. was investigated. Although, the equivalent amount of sodium thiosulfate (S.T.) did not increase the S.N.P. sensibility, its routine use is reconviended, since the combination of S.Th, and even higher doses of S.N.P. were tolerated without metabolic acidosis. As an alternative substance after long-term use of S.N.P. nitroglycerine should be used.

Stereoselective high-performance liquid chromatographic determination of the enantiomers of ketamine and norketamine in plasma.

An enantioselective high-performance liquid chromatographic assay for the quantitation of the enantiomers of ketamine and its major metabolite norketamine in human plasma is described (assay I). The procedure involved extraction of the compounds from alkalized plasma into cyclohexane. Stereoselective separation was achieved with a prepacked alpha 1-acid glycoprotein column without any derivatization procedure. A second assay using a conventional reversed-phase column to determine total (racemic) ketamine and norketamine is also described. Because of interfering plasma peaks (assay II) the cyclohexane solution was reextracted into 1 M hydrochloric acid. The detection wavelength was 215 nm for all substances. The limit of quantification of the method was ca. 40 ng/ml in plasma. The assays were sensitive and reproducible. The method was demonstrated to be sensitive for stereoselective pharmacokinetic studies of ketamine after clinical doses.

Stress hormones in accident patients studied before admission to hospital.

OBJECTIVE: To assess stress hormone response in traumatised patients studied at the site of injury and on their way to hospital. METHODS: The study was prospective. Blood samples were taken from 77 patients immediately after the arrival of the emergency physician at the site of the accident (t1) and shortly before patients' admission to hospital (t2). Plasma concentrations of beta endorphin, cortisol, adrenocorticotrophic hormone (ACTH), prolactin, and growth hormone were measured. RESULTS: Trauma in out-of-hospital patients resulted in remarkably increased concentration of growth hormone within minutes. ACTH, cortisol, and prolactin were only moderately increased. No significant correlations were found between hormone levels and blood pressure or heart rate. The plasma ACTH concentration was significantly lower before admission to hospital than immediately after the accident. Plasma cortisol, prolactin, and growth hormone concentrations were not significantly different between the two points of observation. In samples taken immediately after the accident (t1), there was a positive correlation between both beta endorphin and prolactin and the injury severity score, whereas cortisol levels were negatively correlated with injury severity score, suggesting impaired cortisol release from the adrenal cortex after severe injury. At t1 ACTH was correlated with cortisol and beta endorphin. Patients with head injuries had hormone concentrations similar to those without head injuries but with a similar injury severity score from injuries in other parts of the body. CONCLUSIONS: Lower cortisol concentrations in the very severely injured might be due to failure of the adrenal cortex to respond normally to ACTH stimulation. Growth hormone seems to play a major role in the response to trauma, reflecting an immediate stress response.

Changes in the EEG power spectrum after midazolam anaesthesia combined with racemic or S- (+) ketamine.

Changes in the EEG power spectrum were studied in 50 patients (ASA status I or II), receiving either 2 mg.kg-1 of racemic ketamine or 1 mg.kg-1 of S-(+) ketamine in a randomized and double-blind manner after prior administration of 0.1 mg.kg-1 of midazolam. The patients receiving intramuscular premedication with midazolam about 45 minutes prior to induction of anaesthesia showed, in a deliberately quiet environment and mostly in the early morning, a delta dominated EEG (56% delta power) with a reduced alpha peak (17% alpha power) and an average median of 4 Hz as the baseline findings of the EEG power spectrum. The intravenous administration of midazolam led to activation of the lower beta range (13-18 Hz) and the subsequent injection of ketamine caused an increase in activity in the fast beta range (21-30 Hz), both being accompanied by a reduction of delta power from 56% to 40%. Correspondingly, an increase in the median frequency was noted. Causing nearly the same changes in EEG, S-(+) ketamine was confirmed to be twice as potent as racemic ketamine.

[Multimodal evoked potentials and heart rate variability in comatose patients--1: Method of measuring and normal values]. / Multimodal evozierte Potentiale und Herzratenvariabilität bei komatösen Patienten--Teil 1: Messmethode und Normbereiche.

Multimodal EPs and heart rate variability-measurements in comatose patients have been performed for few years at the university hospitals of Graz and Erlangen. The following data and parameters are analysed and discussed: brainstem auditory evoked potentials, mechanical evoked long-latency SEP, VEP recorded over the central and occipital region and heart rate variability (HRV). The method of data acquisition and processing is described and normative data are introduced. For the long-latency EP-components a signal-to-noise-ratio (SNR) is calculated. SNR is defined as ratio of the largest EP peak-to-peak amplitude and the mean amplitude (standard deviation) of a period prior to the stimulation. An unmeasurable or questionable EP is defined when SNR less than 2.6. For the vertex-SEP the following mean +/- standard deviation was obtained: SNR = 10.6 +/- 4.6; the vertex VEP was calculated with SNR = 7.0 +/- 3.0. The SNR of the bipolar recorded occipitally VEP was 3.9 +/- 2.0. Heart rate variability measurements in normal persons revealed the following mean +/- standard deviation at a heart rate of 67.8/min +/- 10.8/min: HRV = 7.8% +/- 2.5%.