Direct molecular versus culture-based assessment of Gram-positive cocci in biopsies of patients with major abscesses and diabetic foot infections.

Major abscesses and diabetic foot infections (DFIs) are predominant subtypes of complicated skin and skin structure infections (cSSSIs), and are mainly caused by Staphylococcus aureus and ß-hemolytic streptococci. This study evaluates the potential benefit of direct pathogen-specific real-time polymerase chain reaction (PCR) assays in the identification of causative organisms of cSSSIs. One-hundred and fifty major abscess and 128 DFI biopsy samples were collected and microbial DNA was extracted by using the Universal Microbe Detection kit for tissue samples. Pathogen-specific PCRs were developed for S. aureus and its virulence factor Panton-Valentine leukocidin (PVL), Streptococcus pyogenes, S. agalactiae, S. dysgalactiae, and the S. anginosus group. Identification by pathogen-specific PCRs was compared to routine culture and both methods were considered as the gold standard for determination of the sensitivity and specificity of each assay. Direct real-time PCR assays of biopsy samples resulted in a 34 % higher detection of S. aureus, 37 % higher detection of S. pyogenes, 18 % higher detection of S. agalactiae, 4 % higher detection of S. dysgalactiae subspecies equisimilis, and 7 % higher detection of the S. anginosus group, compared to routine bacterial culture. The presence of PVL was mainly confined to S. aureus isolated from major abscess but not DFI biopsy samples. In conclusion, our pathogen-specific real-time PCR assays had a higher yield than culture methods and could be an additional method for the detection of relevant causative pathogens in biopsies.

Polymorphisms in cytokine genes IL6, TNF, IL10, IL17A and IFNG influence susceptibility to complicated skin and skin structure infections.

Complicated skin and skin structure infections (cSSSIs) are caused by Gram-positive and Gram-negative, aerobic and anaerobic pathogens, with a polymicrobial aetiology being frequent. Recognition of invading pathogens by the immune system results in the production of pro- and anti-inflammatory cytokines, which are extremely important for intercellular communication and control of infection. This study assessed whether genetic variation in genes encoding cytokines influences the susceptibility to cSSSIs. For the association study, 318 patients with cSSSI and 328 healthy controls were genotyped for single nucleotide polymorphisms (SNPs) in cytokine genes IL1A, IL1B, IL1RN, TNF, IL10, IL17A, IL17F and IFNG. For immunological validation, peripheral blood mononuclear cells (PBMCs) from 74 healthy individuals, genotyped for SNPs of interest, were stimulated with Staphylococcus aureus or Escherichia coli and corresponding cytokine levels were determined by enzyme-linked immunosorbent assay (ELISA). Polymorphisms IL6 rs1800797, TNF rs1800629, IL10 rs1800871, IL17A rs8193036 and IFNG rs2069705 influenced susceptibility to cSSSIs. No differences in cytokine responses, stratified for genotype, were detected after PBMC stimulation. No association with cSSSIs was observed for polymorphisms IL1A rs17561 and rs1800587, IL1B rs16944 and rs1143627, IL1RN rs4251961, TNF rs361525, IL10 rs1800896, IL17A rs2275913 and IL17F rs763780. In conclusion, polymorphisms in IL6, TNF, IL10, IL17A and IFNG are associated with susceptibility to cSSSIs.

Efficacy and safety of IV/PO moxifloxacin and IV piperacillin/tazobactam followed by PO amoxicillin/clavulanic acid in the treatment of diabetic foot infections: results of the RELIEF study.

OBJECTIVE: The aim was to compare the efficacy and safety of two antibiotic regimens in patients with diabetic foot infections (DFIs). METHODS: Data of a subset of patients enrolled in the RELIEF trial with DFIs requiring surgery and antibiotics were evaluated retrospectively. DFI was diagnosed on the basis of the modified Wagner, University of Texas, and PEDIS classification systems. Patients were randomized to receive either intravenous/oral moxifloxacin (MXF, N = 110) 400 mg q.d. or intravenous piperacillin/tazobactam 4.0/0.5 g t.d.s. followed by oral amoxicillin/clavulanate 875/125 mg b.d. (PIP/TAZ-AMC, N = 96), for 7-21 days until the end of treatment (EOT). The primary endpoint was clinical cure rates in the per-protocol (PP) population at the test-of-cure visit (TOC, 14-28 days after EOT). RESULTS: There were no significant differences between the demographic characteristics of PP patients in either treatment group. At TOC, MXF and PIP/TAZ-AMC had similar efficacy in both the PP and intent-to-treat (ITT) populations: MXF: 76.4 % versus PIP/TAZ-AMC: 78.1 %; 95 % confidence interval (CI) -14.5 %, 9.0 % in the PP population; MXF: 69.9 % versus PIP/TAZ-AMC: 69.1 %; 95 % CI -12.4 %, 12.1 % in the ITT population. The overall bacteriological success rates were similar in both treatment groups (MXF: 71.7 % versus PIP/TAZ-AMC: 71.8 %; 95 % CI -16.9 %, 10.7 %). A similar proportion of patients (ITT population) experienced any adverse events in both treatment groups (MXF: 30.9 % versus PIP/TAZ-AMC: 31.8 %, respectively). Death occurred in three MXF-treated patients and one PIP/TAZ-AMC-treated patient; these were unrelated to the study drugs. CONCLUSION: Moxifloxacin has shown favorable safety and efficacy profiles in DFI patients and could be an alternative antibiotic therapy in the management of DFI. CLINICAL TRIAL: NCT00402727.

Randomised clinical trial of moxifloxacin versus ertapenem in complicated intra-abdominal infections: results of the PROMISE study.

Antibiotic therapy for complicated intra-abdominal infections (cIAIs) should provide broad-spectrum coverage both Gram-positive and Gram-negative microorganisms. The PROMISE study compared the clinical and bacteriological efficacy and safety of moxifloxacin versus ertapenem for the treatment of cIAIs. This randomised, prospective, double-dummy, double-blind, multicentre trial was designed as a non-inferiority study. The safety and efficacy of 5-14 days of daily intravenous moxifloxacin (400mg) or ertapenem (1g) were compared in patients with cIAIs requiring surgery and parenteral antibiotic therapy. The primary and secondary endpoints included clinical and bacteriological responses at 21-28 days after the end of treatment (TOC), respectively. Of 830 enrolled patients, 699 were efficacy valid. Moxifloxacin was non-inferior to ertapenem regarding clinical success [89.5% (315/352) versus 93.4% (324/347); 95% confidence interval (CI) -7.9%, 0.4%]. There were no significant differences between groups for any of the primary causes or types of cIAI regarding clinical response. Bacteriological success was achieved in 86.5% (257/297) of moxifloxacin-treated patients and 90.2% (249/276) of ertapenem-treated patients (95% CI -9.0%, 1.5%). There were no major differences between groups regarding the frequency or types of organisms eradicated. The incidence of adverse events (AEs) was higher with moxifloxacin than ertapenem (P=0.039), however a similar number of drug-related AEs was seen in each group (P=1.000). Wound infections, nausea and increased lipase were the most commonly reported AEs with both agents. The results show that moxifloxacin is a valuable treatment option for a range of community-acquired cIAIs with mild-to-moderate severity.

Efficacy and safety of moxifloxacin in uncomplicated pelvic inflammatory disease: the MONALISA study.

OBJECTIVE: To evaluate the efficacy and safety of moxifloxacin versus levofloxacin plus metronidazole in uncomplicated pelvic inflammatory disease (uPID) in Asia. DESIGN: Prospective, randomised, double-blind, double-dummy, parallel-group study. SETTING: Multicentre, multinational study in the inpatient and/or outpatient setting. POPULATION: Women (aged ≥18 years) with uPID (defined as PID with no pelvic or tubo-ovarian abscess on pelvic ultrasonography and at laparoscopic examination) and not requiring intravenous treatment. METHODS: Women received a 14-day course of either oral moxifloxacin, 400 mg once daily, or oral levofloxacin, 500 mg once daily, plus oral metronidazole, 500 mg twice daily. Additionally, a single dose of ceftriaxone, 250 mg intramuscularly, was administered to women who had a positive screening test for Neisseria gonorrhoeae. MAIN OUTCOME MEASURES: The primary measure of efficacy was clinical response at test-of-cure (TOC) (7-14 days after the last dose of study drug) in the per-protocol population. Non-inferiority of moxifloxacin to the comparator regimen was demonstrated if lower limit of 95% CI was >-15%. Other measures were clinical response during therapy and at 4-week follow up, microbiological response at TOC, and safety. RESULTS: A total of 460 women were randomised to the study. For the primary measure of efficacy (clinical cure at TOC), moxifloxacin was noninferior to levofloxacin plus metronidazole (moxifloxacin: 152/194, 78.4%; comparator 155/190, 81.6%; 95% CI -10.7 to +4.9). The most commonly isolated pathogens at baseline included Neisseria gonorrhoeae, Chlamydia trachomatis, Escherichia coli, Staphylococcus aureus, Peptostreptococcus spp., Proteus mirabilis, Streptococcus agalactiae and Klebsiella pneumoniae. Bacteriological success rates were high and comparable between treatment arms (microbiologically valid populations, moxifloxacin 27/30, 90.0%; comparator 22/26, 84.6%; 95% CI -12.7 to +20.3). Both treatments were well tolerated. CONCLUSIONS: Moxifloxacin monotherapy, 400 mg once daily for 14 days, is an effective and well-tolerated oral treatment for women with uPID.

Efficacy and safety of sequential intravenous/oral moxifloxacin vs intravenous/oral amoxicillin/clavulanate for complicated skin and skin structure infections.

BACKGROUND: Complicated skin and skin structure infections (cSSSIs) are an important healthcare concern worldwide, as they can be life-threatening and challenging to treat. cSSSIs are normally managed using a combination of surgical intervention and prompt antibiotic use. New therapeutic options, including novel antibiotics, are required to improve outcomes in terms of duration of illness and to reduce the consumption of healthcare resources. METHODS: This was a prospective, randomized, open-label, parallel-group, multinational clinical study comparing sequential intravenous/oral (iv/po) moxifloxacin, 400 mg once daily, and iv amoxicillin/clavulanate, 1,000 mg/ 200 mg three times daily followed by po amoxicillin/ clavulanate, 500 mg/125 mg three times daily, for 7-21 days in hospitalized patients. RESULTS: A total of 804 patients were enrolled (mean age 51.8 years). The most common clinical diagnosis was complicated erysipelas (32.1% moxifloxacin; 30.0% amoxicillin/ clavulanate) and major abscess (31.1% moxifloxacin; 29.3% amoxicillin/clavulanate). Overall clinical success rates at the test-of-cure (TOC) visit (14-28 days post-treatment) for the per-protocol population (primary efficacy variable) were 80.6% (254/315) for patients in the moxifloxacin group and 84.5% (268/317) for those receiving amoxicillin/clavulanate (95% confidence interval [CI] -9.41, 2.18). Similar results were obtained for the intention-to-treat population (95% CI -7.56, 4.31). In both treatment groups, the highest clinical success rates were recorded for patients with complicated erysipelas, major abscess, surgical wound infection, and cellulitis. The lowest clinical cure rates were reported for diabetic foot infection and necrotizing fasciitis. In the microbiologically evaluable population, the bacteriological success rate (eradication and presumed eradication) was 76.0% (127/ 167) in the moxifloxacin group and 81.4% (140/172) in the amoxicillin/clavulanate group (95% CI -12.96, 4.41). Staphylococcus aureus (137 isolates) and Escherichia coli (50 isolates) were the most frequently isolated skin pathogens. Adverse event rates were comparable between treatment groups. CONCLUSIONS: Treatment with sequential iv/po moxifloxacin monotherapy once daily is clinically comparable to that with iv/po amoxicillin/clavulanate three times daily in the management of cSSSIs. Moxifloxacin's simple dose regimen offers an advantage over amoxicillin/clavulanate and represents a valuable addition to current antibiotic regimens used in the treatment of cSSSIs.

Moxifloxacin for the treatment of patients with complicated intra-abdominal infections (the AIDA Study).

This prospective, randomized, open, international, multicenter study of adults with complicated intra-abdominal infections (cIAI) compared the efficacy and safety of sequential intravenous (i.v.) to oral (p.o.) moxifloxacin 400 mg once daily, with that of i.v. ceftriaxone 2 g once daily, plus metronidazole 500 mg three times daily, followed by p.o. amoxicillin/clavulanate 625 mg three times daily. The primary efficacy variable was clinical cure at test of cure (TOC) (day 28-42 after study entry) in the per protocol (PP) population. Of 595 patients in the study, 511 patients were valid for PP analysis (246 moxifloxacin, 265 ceftriaxone/metronidazole). Sequential moxifloxacin was noninferior to the comparator regimen--clinical cure rates at TOC were 80.9% versus 82.3% (moxifloxacin versus ceftriaxone/metronidazole; 95% CI -8.9, 4.2%). The incidence of adverse events was comparable between the two treatment groups. Therefore, sequential moxifloxacin monotherapy is as effective and safe as combination therapy with i.v. ceftriaxone plus i.v. metronidazole followed by oral amoxicillin/clavulanate for the treatment of cIAI.

Moxifloxacin vs ampicillin/sulbactam in aspiration pneumonia and primary lung abscess.

BACKGROUND: Aspiration pneumonia (AP) and primary lung abscess (PLA), are diseases following aspiration of infectious material from the oropharynx or stomach. An antibiotic therapy, also covering anaerobic pathogens, is the treatment of choice. In this study we compared moxifloxacin (MXF) and ampicillin/sulbactam (AMP/SUL) concerning efficacy and safety in the treatment of AP and PLA. METHODS: Patients with pulmonary infections following aspiration were included in a prospective, open-label, randomized, multicenter trial. Sequential antibiotic therapy with MXF or AMP/SUL was administered until complete radiologic and clinical resolution. RESULTS: A total of 139 patients with AP and PLA were included, 96 were evaluable for efficacy (EE, 48 patients in each treatment group). The overall clinical response rates in both groups were numerically identical (66.7%). MXF and AMP/SUL were both well tolerated, even after long-term administration [median duration of treatment (range) in days MXF versus AMP/SUL: AP 11 (4-45) vs 9 (3-25), PLA 30.5 (7-158) vs 35 (6-90)]. CONCLUSION: In the treatment of aspiration-associated pulmonary infections moxifloxacin appears to be clinically as effective and as safe as ampicillin/sulbactam; but, however, having the additional benefit of a more convenient (400 mg qd) treatment.

Moxifloxacin versus ofloxacin plus metronidazole in uncomplicated pelvic inflammatory disease: results of a multicentre, double blind, randomised trial.

OBJECTIVE: This multinational, multicentre, prospective, randomised, double blind, parallel group, non-inferiority study compared the efficacy and safety of moxifloxacin monotherapy with ofloxacin plus metronidazole in women with uncomplicated pelvic inflammatory disease. METHODS: Women from hospitals throughout 13 countries received a 14 day course of either oral moxifloxacin, 400 mg once daily (n = 384), or oral ofloxacin, 400 mg twice daily plus oral metronidazole, 500 mg twice daily (n = 365). RESULTS: Of the 741 patients in the intent to treat (ITT) population, 564 (74.2%) were valid for the per protocol (PP) analyses; 112 (19.9%) of these were included in the microbiologically valid population (MBV). Clinical resolution rates in the PP population at the test of cure visit (TOC, 5-24 days post-therapy, primary efficacy end point) were 90.2% (248/275) for moxifloxacin and 90.7% (262/289) for ofloxacin plus metronidazole (95% CI: -5.7% to 4.0%). At follow up (28-42 days post-therapy), resolution rates in the PP population were 85.8% (236/275) and 87.9% (254/289) for moxifloxacin and comparator, respectively (95% CI: -8.0% to 3.1%). Bacteriological success rates in the MBV population at TOC were 87.5% (49/56) for moxifloxacin and 82.1% (46/56) for comparator (95% CI: -8.3% to 18.8%). Against Chlamydia trachomatis and Neisseria gonorrhoeae, bacteriological success rates with moxifloxacin were 88.5% (23/26) and 100% (13/13) and for comparator 85.7% (18/21) and 81.8% (18/22), respectively. Drug related adverse events occurred less frequently with moxifloxacin (22.5% (85/378)) versus the comparator (30.9% (112/363)) (p = 0.01). CONCLUSION: In uncomplicated PID, once daily moxifloxacin monotherapy was clinically and bacteriologically as efficacious as twice daily ofloxacin plus metronidazole therapy and was associated with fewer drug related adverse events.

A multinational, multicentre, non-blinded, randomized study of moxifloxacin oral tablets compared with co-amoxiclav oral tablets in the treatment of acute exacerbation of chronic bronchitis.

The aim of this study was to compare the efficacy and safety of once daily dosing with moxifloxacin (BAY 12-8039) with that of coamoxiclav given three times daily for the treatment of acute exacerbation of chronic bronchitis (AECB). Moxifloxacin (one 400 mg tablet daily) was administered orally for 5 days and co-amoxiclav (three 625 mg tablets daily) was given orally for 7 days. The study was randomized, non-blinded, multinational (12 countries) and multicentre (68 centres). A total of 575 patients, all with clear signs of AECB, were treated, 292 with moxifloxacin and 283 with co-amoxiclav. Of these, 512 patients were evaluable for efficacy (261 in the moxifloxacin group and 251 in the co-amoxiclav group). The primary efficacy parameter was clinical response at 14 days in the evaluable population. A clinical success was classified as resolution or improvement of symptoms. Variables used to assess clinical response included wheeze, cough, dyspnoea, sputum volume, rales and rhonchi. The success rate for moxifloxacin in the evaluable patients was 96.2% and that for co-amoxiclav was 91.6%. The 95% confidence intervals for this difference (0.4%; 8.7%) indicate equivalence in the treatments. Sputum samples were taken from patients and 140 of these contained a pathogen, Haemophilus influenzae being the most frequently isolated. Moraxella catarrhalis and Streptococcus pneumoniae were also commonly isolated pathogens. The eradication rate at 14 days in the evaluable patients was 87.7% in the moxifloxacin group and 89.6% in the coamoxiclav group. Both drugs were well tolerated with no significant differences in the numbers of drug-related adverse events or the numbers of patients withdrawing because of an adverse event. These results and the broad spectrum of antibacterial activity make moxifloxacin a promising and safe alternative to conventional therapy for the empirical treatment of AECB.

[Anesthetic complications. The incidence of severe anesthetic complications in patients and families with progressive muscular dystrophy of the Duchenne and Becker types]. / Narkosezwischenfälle. Inzidenz schwerer Narkosezwischenfälle bei Patienten und in Familien mit progressiven Muskeldystrophien vom Typ Duchenne und Becker.

UNLABELLED: During the last 30 years a great number of case reports presented severe anaesthetic complications with sudden cardiac arrest in patients with muscular dystrophies, mostly unsuspected at the time of the event. As succinylcholine was involved in the majority of the intractable incidents with lethal outcome the Food and Drug Administration (FDA) of the United States recommended a warning of the administration of succinylcholine in young children and adolescents in 1992 and an extensive international discussion on the routine use of succinylcholine in paediatric anaesthesia. Epidemiological studies on this issue are rare. We projected an inquiry about the incidence rate and type of severe anaesthetic complications in an utmost large number of patients and families with Duchenne (DMD) and Becker type (BMD) muscular dystrophy. METHODS: With the approval of the ethic committee of the university Witten/Herdecke and informed consent of the participants we investigated all patients and families who were diagnosed, controlled and treated for DMD or BMD as inpatients or outpatients in a "Muscle Centre" since 1983. The questionnaire asked for the number of patients per family, classification of the disease DMD or BMD, number and date of anaesthetics in the patients and eventual complications, anaesthetics and eventual complications in the parents, siblings and relatives and the occurrence of malignant hyperthermia (MH) in the family or relatives. Statistical assessments were done by Fisher's exact test for stratified 2 x 2 tables and Zelen's test for homogeneity of odds ratios. RESULTS: 200 out of 224 questionnaires could be evaluated. The diagnosis was confirmed by molecular genetic and immunohistochemical investigations. In 147 families it turned out to be DMD, in 53 families BMD. The 212 male and 9 female patients in the 200 families were given 444 anaesthetics. Sudden cardiac arrest occurred in 6 patients, all successfully resuscitated. Nine less severe incidents consisted of fever, symptoms of rhabdomyolysis (CK-elevation, dark coloured urine, hyperkalemia) and masseter spasm. The statistical assessment revealed that the occurrence of an event was highly dependent whether the diagnosis of muscular dystrophy was established or not (p < 0.0001, Fisher's exact test). All six cardiac arrests occurred in the 45 families with undiagnosed disease and no event happened in the 134 families with already known DMD/BMD. There was evidence that the number of anaesthetics without prior establishment of the diagnosis decreased after 1992 (p = 0.004, Fisher's exact test). CONCLUSIONS: Our results demonstrate that severe incidents and cardiac arrests occurred only in young children with undiagnosed DMD or BMD who received inhalational agents and succinylcholine. A cardiac arrest in 6 out of 200 families was found much more frequently than in the normal paediatric population (about 1:1000 to 1:3000). The decrease of events after 1992 (warning of the FDA) and disappearance of sudden cardiac arrests in our group of patients might be due to the world wide discussion on routine use of succinylcholine in children or the much earlier establishment of the diagnosis in our population. An early diagnosis of DMD and BMD and the avoidance of the triggering agents succinylcholine and volatile anaesthetics can reduce the risk of severe anaesthetic complications.

Treatment of hypertensive emergency. Comparison of a new dosage form of the calcium antagonist nitrendipine with nifedipine capsules.

OBJECTIVE: To present the efficacy and tolerability of a new oral dosage form of the calcium antagonist nitrendipine compared to nifedipine capsules in patients with hypertensive emergency. DESIGN: Multicenter randomized double blind clinical study. SETTING: 23 study centres (hospitals) in Germany. PATIENTS: 161 patients between 20 and 70 years with acutely elevated blood pressure (systolic 200-250 mmHg, diastolic between 110-140 mmHg) with and without concomitant clinical symptoms. INTERVENTIONS: Double blind treatment with 10 mg nifedipine or 5 mg nitrendipine. Nifedipine was administered as capsules, nitrendipine was given from a small plastic tube (vial), containing 1 ml alcoholic solution. Every patient received in addition to the test medication a placebo corresponding to the other product. Patients with insufficient treatment after 45 min were given either an additional capsule of 10 mg nifedipine or a further vial containing 5 mg nitrendipine according to their group and maintaining the double dummy procedure. MEASUREMENTS AND RESULTS: Blood pressure and heart rate were measured repeatedly during 4 h, before and 90 min after beginning of the treatment a 12 channel resting ECG was recorded. At 45 min after administration the blood pressure had fallen significantly from 216.0/117.4 mmHg to 170.0/93.3 mmHg under nifedipine and from 216.9/117.3 mmHg to 177.4/94.4 mmHg under nitrendipine. 61.6% of the nifedipine patients and 58.8% of the nitrendipine patients had already reached blood pressure values < 180/100 mmHg after 45 min and in both groups 83% of these patients were still in this limit at the end of the observation period after 4 h. Tolerability was very good in both groups. CONCLUSION: The new dosage form of nitrendipine (vial with 1 ml of alcoholic solution) represents an alternative in the treatment of hypertensive emergency.

[Sensitivity and specificity of multi-frequency oscillation methods, body plethysmography and spirometry in 5-8-year-old asthmatic patients]. / Sensitivität und Spezifität von polyfrequenter Oszillationsmethode, Bodyplethysmographie und Spirometrie bei Asthmatikern im Alter von 5-8 Jahren.

We compared specificity and sensitivity of the forced oscillation technique with the standard methods of body plethysmography and spirometry in children suffering from asthma (age 5-8 yrs). We investigated 60 healthy and 66 asthmatic children by forced oscillation, plethysmography and spirometry. Mean FEV1% pred was 99.7 and 82.4% in the healthy and asthmatic subjects, respectively, and mean SRaw was 0.68 and 1.18 kPa*s, respectively. Forced oscillation and plethysmography could be measured in all children, whereas 29% of the investigated children failed to perform valid spirometry. Discriminant analysis was used to compare the optimal classification which could be obtained from the measured data with the clinical one. Fixing specificity to 95%, we computed sensitivities of 66% (forced oscillation), 68% (body plethysmography), and 76% (spirometry). We conclude that the diagnostic value of the three methods in young children with asthma is similar. However, the value of spirometry is limited by cooperation in these young children.

Effect of gamma-hydroxybutyrate on the reactivity of pial arteries before and after ischemia.

The effect of gamma-hydroxybutyrate (GHB) on the reactivity of pial arteries to local metabolic factors was tested in chloralose-anesthetized cats before or after a period of transient ischemia induced by air embolism. The vascular reactions were determined during the perivascular microapplication of artificial CSFs with increasing concentrations of adenosine (10(-11)-10(-3) M), H+ (pH 5.1-7.6), or K+ (0-10 mM). During nonischemic conditions the pial arterial reactivity to adenosine and H+, but not to K+, was significantly increased by GHB (250 mg/kg i.v.) when compared with the control reactivity. After cerebral ischemia the reactivity to adenosine was abolished with and without the administration of GHB prior to air embolism. The reactivity to K+ was partly preserved but not increased by GHB when compared with previous results without GHB. In contrast GHB improved the postischemic reactivity to perivascular H+ that had been found to be abolished in previous experiments without GHB. The perivascular microapplication of GHB showed no influence of GHB on the vascular diameter. An important finding of the present study is the demonstration of an increase in cerebrovascular reactivity, which may give scope for therapeutic improvement of the regulation of CBF in pathophysiological conditions.

[Anterior fontanelle as a window to the brain--normal values and timing of closure]. / Die grosse Fontanelle als Fenster zum Gehirn--Normalwerte und Verschlusszeiten.

Nowadays an exact examination of the infant's brain is possible through the anterior fontanelle by ultrasonography (US); however for that a certain minimal size of the fontanelle is necessary. In the literature standards for size and timing of closure are scarce. In the Bonn Longitudinal Study of growth and development of preterm infants in comparison with full term infants also the length (anterior-posterior diameter) and width (transversal) of the anterior fontanelle have been measured monthly from birth, and the timing of closure was registered. As a measure of fontanelle size here the width (transversal diameter) is used. For the full term infants the width (50. percentile) at birth is 2.0 cm; it decreases to 0.6 cm until the age of 12 months. The great variability of fontanelle size observed in the Bonn study is also confirmed in the literature. In the appropriate for gestational age (AGA) preterm infants the anterior fontanelle (50. percentile) increases between 32 and 40 postmenstrual weeks from 1.8 to 2.5 cm and is then significantly greater than in the full term infants. At least at the age of 3 months there is no significant difference between the AGA preterm infants and the full term infants, either for the boys or for the girls. For the boys, in spite of their significantly greater head circumference there is a tendency to have a smaller fontanelle than the girls; the difference is at no age significant. For preterm as well as for full term infants timing of closure occurs somewhat earlier in the boys than in the girls.(ABSTRACT TRUNCATED AT 250 WORDS)

Factors predicting the therapeutic outcome of duodenal ulcer treatment with H2-receptor antagonists.

In a prospective trial 37 duodenal ulcer patients were treated daily with 1 g cimetidine. Personal and clinical data were obtained for all patients, acid secretion studies performed before and during treatment, and pharmacokinetic parameters of cimetidine determined. The healing rate after 4 weeks was 64.9% (24 patients). Non-Responders included a higher proportion of smokers, patients with a history of ulcer and previous treatment with H2-receptor antagonists than Responders. Basal acid output (BAO) and peak acid output (PAO) values were not different between the two groups, nor was the reduction of BAO and PAO under cimetidine. However, more Responders had complete suppression of BAO than Non-Responders. A correlation existed in both groups between cimetidine plasma concentration and PAO suppression but not with BAO suppression. Regular drug intake (compliance) was found in about 90% in both groups. Cimetidine bioavailability parameters were identical in both groups, but Non-Responders had a higher peak concentration and a shorter time of peak concentration. Discriminant analysis enabled a prediction of treatment response in 89.2% of the patients by using five factors: time of peak concentration of cimetidine, previous H2-receptor-antagonist treatment, peak concentration, smoking, and alcohol use. Prediction of treatment response is increased by use of drug related variables.

[Reference values of sodium, potassium, calcium, chloride and inorganic phosphate excretion in 24-hour urine of healthy children]. / Referenzwerte der Natrium-, Kalium-, Kalzium-, Chlorid- und anorganischen Phosphat-Ausscheidung im 24 h-Urin gesunder Kinder.

Excretion of sodium, potassium, calcium, chloride and inorganic phosphate was determined in 24 h urine of 157 healthy children (ages 6-14 years). The diet was not controlled. The statistical age- and sexspecific investigation of the results (mval/24 h, mval/24 h/mg creatinine) showed significant differences.