[Vibrio vulnificus, an increasing threat of sepsis in Germany?] / Vibrio vulnificus, eine zunehmende Sepsisgefahr in Deutschland?

BACKGROUND: The prevalence of Vibrio vulnificus heavily depends on the temperature and salinity of the sea water. In the course of climate change an increase in cases of fatal sepsis caused by V. vulnificus at the German Baltic Sea coast could be detected. OBJECTIVE: To generate awareness for a life-threatening infection with increasing incidence in Germany. MATERIAL AND METHODS: This article presents an overview of the current state of the literature followed by an exemplary description of cases with V vulnificus sepsis caused by contact with water in the Baltic Sea, which were treated at the Medical University in Greifswald in summer 2018. RESULTS: In the presence of risk factors, such as liver and kidney diseases, immunosuppression and male sex, there is a danger of severe sepsis if damaged skin comes into contact with contaminated sea water. A pronounced organ dysfunction can frequently be found on admission. In these cases the diagnosis must be made promptly and timely surgical cleansing and antibiotic treatment should be initiated (e.g. a combination of tetracyclines and third generation cephalosporins). CONCLUSION: Sepsis due to V. vulnificus will probably increase over the coming years. Because there is a latency in some cases between infection and onset of sepsis, physicians beyond the coastal region must also be informed about this disease.

Impact of antibiotic administration on blood culture positivity at the beginning of sepsis: a prospective clinical cohort study.

OBJECTIVES: Sepsis guidelines recommend obtaining blood cultures before starting anti-infective therapy in patients with sepsis. However, little is known of how antibiotic treatment before sampling affects bacterial growth. The aim of this study was to compare the results of blood cultures drawn before and during antibiotic therapy. METHODS: Prospective clinical cohort study of septic patients. Adult intensive care unit patients with two or three blood culture sets at the beginning of sepsis between 2010 and 2017 were included. Patients with blood culture samples obtained before antibiotic therapy were compared with patients with samples taken during antibiotic therapy. Blood culture positivity, defined as presence of a microbiological pathogen, was compared between the groups. Logistic regression was performed to adjust the impact of different factors with respect to blood culture positivity. RESULTS: In total, 559 patients with 1364 blood culture sets at the beginning of sepsis were analysed. Blood culture positivity was 50.6% (78/154) among patients with sepsis who did not receive antibiotics and only 27.7% (112/405) in those who were already receiving antibiotics (p <0.001). Logistic regression revealed antibiotic therapy as an independent factor for less pathogen identification (odds ratio 0.4; 95% CI 0.3-0.6). Gram-positive pathogens (28.3% (111/392) versus 11.9% (116/972); p <0.001) and also Gram-negative pathogens (16.3% (64/392) versus 9.3% (90/972); p <0.001) were more frequent in blood culture sets drawn before antibiotic therapy compared with sets obtained during antibiotic therapy. CONCLUSIONS: Obtaining blood cultures during antibiotic therapy is associated with a significant loss of pathogen detection. This strongly emphasizes the current recommendation to obtain blood cultures before antibiotic administration in patients with sepsis.

[Sepsis detection in emergency medicine : Results of an interprofessional survey on sepsis detection in prehospital emergency medicine and emergency departments]. / Sepsis erkennen im Rettungsdienst : Ergebnisse einer interprofessionellen Befragung zur präklinischen und frühen innerklinischen Sepsiserkennung.

BACKGROUND: Sepsis is associated with a high mortality, which can be reduced by starting screening, diagnostics and treatment as early as possible. Due to multiple educational programs and increased awareness, a decreased sepsis mortality on intensive care units has been achieved. Many patients with sepsis are admitted by the prehospital emergency service to hospital emergency departments. Thus, prehospital emergency services and emergency departments provide an opportunity to start screening, diagnosis and treatment earlier. OBJECTIVES: To detect sepsis it is paramount that emergency personnel are aware of the disease and have a profound knowledge regarding symptoms, screening and diagnostics. The objective of this survey was to examine the state of knowledge regarding sepsis among staff working in emergency medicine. MATERIAL AND METHODS: To assess the awareness and knowledge, a paper-based, anonymous survey was conducted among prehospital and emergency department personnel from May to August 2017 in northeastern Germany. Testing of significance was carried out using the χ2-testand Fisher's exact test. RESULTS: Out of 411 persons polled 212 answered (response rate 51.6%) and 24 questionnaires were incomplete and thus excluded. A total of 188 questionnaires were included covering 55 emergency physicians, 23 nurses, 82 paramedics and 19 emergency dispatchers. On a 4-point Likert scale 100% of emergency doctors, 96% of nurses, 84% of paramedics and 84% of emergency dispatchers considered early initiation of sepsis treatment to be important. Additionally, 92% of emergency physicians and 65% of nurses had attended educational programs on sepsis within the last year, which is significantly higher than among paramedics (19%, p < 0.01) and emergency dispatchers (21%, p = 0.025). In addition, 38% of paramedics and 47% of emergency dispatchers had never attended lectures on sepsis. The quick sequential (sepsis-related) organ failure assessment (qSOFA) was known by 80% of emergency doctors, thus, significantly more often than by nurses (26%), paramedics (29%) and emergency dispatchers (29%, p < 0.01). The emergency personnel were asked to tick all symptoms they associated with sepsis from a display of 14 symptoms. Among all occupation groups the majority selected "increased body temperature", "drop in blood pressure" and "altered breathing". In relation to "increased body temperature" the symptom "altered mental status" was selected significantly more frequently by emergency doctors than by nurses and paramedics (p = 0.02 and p < 0.01, respectively). The combination of at least all 3 qSOFA parameters was selected significantly more often by emergency doctors (62%) than by nurses (13%) and paramedics (10%, p = 0.017 and p < 0.01, respectively). CONCLUSION: Although emergency personnel rated an early initiation of sepsis treatment as important, sepsis knowledge was limited. While the majority of emergency doctors and many nurses had attended educational programs on sepsis within the last year, an alarmingly high percentage of paramedics and emergency dispatchers had never received sepsis education. Emergency personnel are mostly unfamiliar with the qSOFA score and did not associate an altered mental status with sepsis. In light of the high sepsis morbidity and mortality, further achievements might be made by initiating sepsis screening and diagnostics in the prehospital setting. Analogous to advancements in intensive care units, increased educational programs for emergency personnel might lead to an earlier detection and improved prognosis of sepsis.

Continuing chronic beta-blockade in the acute phase of severe sepsis and septic shock is associated with decreased mortality rates up to 90 days.

BACKGROUND: There is growing evidence that beta-blockade may reduce mortality in selected patients with sepsis. However, it is unclear if a pre-existing, chronic oral beta-blocker therapy should be continued or discontinued during the acute phase of severe sepsis and septic shock. METHODS: The present secondary analysis of a prospective observational single centre trial compared patient and treatment characteristics, length of stay and mortality rates between adult patients with severe sepsis or septic shock, in whom chronic beta-blocker therapy was continued or discontinued, respectively. The acute phase was defined as the period ranging from two days before to three days after disease onset. Multivariable Cox regression analysis was performed to compare survival outcomes in patients with pre-existing chronic beta-blockade. RESULTS: A total of 296 patients with severe sepsis or septic shock and pre-existing, chronic oral beta-blocker therapy were included. Chronic beta-blocker medication was discontinued during the acute phase of sepsis in 129 patients and continued in 167 patients. Continuation of beta-blocker therapy was significantly associated with decreased hospital (P=0.03), 28-day (P=0.04) and 90-day mortality rates (40.7% vs 52.7%; P=0.046) in contrast to beta-blocker cessation. The differences in survival functions were validated by a Log-rank test (P=0.01). Multivariable analysis identified the continuation of chronic beta-blocker therapy as an independent predictor of improved survival rates (HR = 0.67, 95%-CI (0.48, 0.95), P=0.03). CONCLUSIONS: Continuing pre-existing chronic beta-blockade might be associated with decreased mortality rates up to 90 days in septic patients.

Assessment of N2O emissions from a fertilised vegetable cropping soil under different plant residue management strategies using 15N tracing techniques.

Combined application of plant residues and N fertilisers strongly affect soil mineral N dynamics and N2O emissions depending on the quality of the plant residues, their application methods and other management strategies. We investigated the effect of combined application of two vegetable plant residues (cauliflower and sweet corn) and 15N fertiliser on N dynamics and N2O emission in a glasshouse pot study. The experiment was conducted under two residue management practices (soil incorporation vs surface mulching) over 98days with growing basil (Ocimum basilicum) plants. We also assessed the efficacy of applying the nitrification inhibitor, 3,4-dimethylpyrazole phosphate (DMPP) to the plant residues, for reducing N loss and mitigating N2O emissions. Application of plant residues, both on the soil surface or into soil, resulted in net N mineralisation and increased cumulative N2O emission compared with the application of N fertiliser alone. Soil surface mulching of sweet corn decreased total and residue-induced cumulative N2O emission compared with the incorporation method, while it showed opposite effect on N2O emissions from cauliflower residue. The application of DMPP with sweet corn residue reduced total, residue- and fertiliser-induced N2O emissions; however its application with cauliflower residue did not show any mitigating effect on the N2O emissions. The residue application methods and the use of DMPP did not significantly affect 15N recovery by the basil plants. In contrast, soil incorporation of these residues doubled the microbial immobilisation of applied 15N into soil organic matter. Linear regression analysis of N2O emission during the experimental period indicated that in the treatments without DMPP application, soil NO3--N concentration was the most important factor in controlling the magnitude of N2O emissions, while the application of DMPP changed the dominant regulating factor from NO3--N to NH4+-N concentration.

Sampling frequency affects estimates of annual nitrous oxide fluxes.

Quantifying nitrous oxide (N2O) fluxes, a potent greenhouse gas, from soils is necessary to improve our knowledge of terrestrial N2O losses. Developing universal sampling frequencies for calculating annual N2O fluxes is difficult, as fluxes are renowned for their high temporal variability. We demonstrate daily sampling was largely required to achieve annual N2O fluxes within 10% of the 'best' estimate for 28 annual datasets collected from three continents--Australia, Europe and Asia. Decreasing the regularity of measurements either under- or overestimated annual N2O fluxes, with a maximum overestimation of 935%. Measurement frequency was lowered using a sampling strategy based on environmental factors known to affect temporal variability, but still required sampling more than once a week. Consequently, uncertainty in current global terrestrial N2O budgets associated with the upscaling of field-based datasets can be decreased significantly using adequate sampling frequencies.

Rainfall variability drives interannual variation in N2O emissions from a humid, subtropical pasture.

Variations in interannual rainfall totals can lead to large uncertainties in annual N2O emission budget estimates from short term field studies. The interannual variation in nitrous oxide (N2O) emissions from a subtropical pasture in Queensland, Australia, was examined using continuous measurements of automated chambers over 2 consecutive years. Nitrous oxide emissions were highest during the summer months and were highly episodic, related more to the size and distribution of rain events than soil water content. Over 48% of the total N2O emitted was lost in just 16% of measurement days. Interannual variation in annual N2O estimates was high, with cumulative emissions increasing with decreasing rainfall. Cumulative emissions averaged 1826.7±199.9 g N2O-N ha(-1) yr(-1) over the two year period, though emissions from 2008 (2148±273 g N2O-N ha(-1) yr(-1)) were 42% higher than 2007 (1504±126 g N2O-N ha(-1) yr(-1)). This increase in annual emissions coincided with almost half of the summer precipitation from 2007 to 2008. Emissions dynamics were chiefly driven by the distribution and size of rain events which varied on a seasonal and annual basis. Sampling frequency effects on cumulative N2O flux estimation were assessed using a jackknife technique to inform future manual sampling campaigns. Test subsets of the daily measured data were generated for the pasture and two adjacent land-uses (rainforest and lychee orchard) by selecting measured flux values at regular time intervals ranging from 1 to 30 days. Errors associated with weekly sampling were up to 34% of the sub-daily mean and were highly biased towards overestimation if strategically sampled following rain events. Sampling time of day also played a critical role. Morning sampling best represented the 24 hour mean in the pasture, whereas sampling at noon proved the most accurate in the shaded rainforest and lychee orchard.

[Overwhelming postsplenectomy infection syndrome]. / Fulminante Pneumokokkensepsis nach Splenektomie.

The overwhelming postsplenectomy infection syndrome (OPSI) is a fulminant sepsis that is mainly caused by Streptococcus pneumoniae and is characterized by a particular high mortality. Patients whose spleen was removed due to a hematological disease are at special risk. Even after the recommended immunization against Streptococcus pneumoniae 20-30 % of these patients do not develop an adequate level of antibody response. Therefore, this particular group of patients must be trained how to behave in case of fever and need to obtain immediate specific sepsis therapy with antibiotic prophylaxis.

Pyrolysing poultry litter reduces N2O and CO2 fluxes.

Application of poultry litter (PL) to soil can lead to substantial nitrous oxide (N2O) emissions due to the co-application of labile carbon (C) and nitrogen (N). Slow pyrolysis of PL to produce biochar may mitigate N2O emissions from this source, whilst still providing agronomic benefits. In a corn crop on ferrosol with similarly matched available N inputs of ca. 116 kg N/ha, PL-biochar plus urea emitted significantly less N2O (1.5 kg N2O-N/ha) compared to raw PL at 4.9 kg N2O-N/ha. Urea amendment without the PL-biochar emitted 1.2 kg N2O-N/ha, and the PL-biochar alone emitted only 0.35 kg N2O-N/ha. Both PL and PL-biochar resulted in similar corn yields and total N uptake which was significantly greater than for urea alone. Using stable isotope methodology, the majority (~80%) of N2O emissions were shown to be from non-urea sources. Amendment with raw PL significantly increased C mineralisation and the quantity of permanganate oxidisable organic C. The low molar H/C (0.49) and O/C (0.16) ratios of the PL-biochar suggest its higher stability in soil than raw PL. The PL-biochar also had higher P and K fertiliser value than raw PL. This study suggests that PL-biochar is a valuable soil amendment with the potential to significantly reduce emissions of soil greenhouse gases compared to the raw product. Contrary to other studies, PL-biochar incorporated to 100mm did not reduce N2O emissions from surface applied urea, which suggests that further field evaluation of biochar impacts, and methods of application of both biochar and fertiliser, are needed.

Effect of different sample volumes on the DNA extraction of Aspergillus fumigatus from whole blood.

Five methods were compared, using conventional PCR, for the isolation of DNA from Aspergillus fumigatus conidia from 1-3-mL samples of whole blood. A lower detection threshold of Aspergillus conidia was achieved using 3-mL rather than 1-mL samples with three of five methods tested.

Development of an opto-electronic positioning device for serial direct digital images of oral structures.

The aim of this study was to develop and test in vitro an opto-electronic positioning device for serial direct digital images of oral structures, i.e. to associate direct digital imaging with the principles of computer-aided surgery. This system registered positions of infrared light emitting diodes (LED) on carriers, establishing local coordinate systems. With LED markers attached on the sensor holder, the X-ray tube and a fix reference, the opto-electronic camera (Optotrak) registered the geometric source/detector relation. A specially designed tracking and guidance software was developed which enabled the operator to reposition the X-ray source. A graphical user interface guided the operator in aligning 2 circles to the reference axis, one indicating the origin of the beam, the other its tip. In addition, depth control was provided. An in vitro calibration was performed. A sensor holder/bite block carried the Sens-A-Ray sensor with a hair-cross. In front of the object a second hair-cross was fixed. A steel ball fixed to the center of the X-ray cone allowed to verify the alignment. The mean angulation error in the vertical plane was 0.06 degrees and 0.04 degrees in the horizontal one. Translation mean errors were small and ranged between -0.02 mm and 0.37 mm. The translation in the Z axis is negligible. This resulted in pairs of images suitable for digital subtraction. Although still in an experimental state, the results showed that opto-electronic navigation was useful to standardize projection geometry without any mechanical link and to achieve digital subtraction images based on direct digital imaging.

Angiotensin II and intracellular calcium of adult cardiac fibroblasts.

In various cardiovascular disorders, circulating or myocardial angiotensin II (Ang II) levels are increased, leading to excess collagen synthesis of cardiac fibroblasts. To characterize signal transduction mechanisms of Ang II, we examined changes in intracellular Ca2+ concentration ([Ca2+]i) of fura-2-loaded cultured adult rat cardiac fibroblasts by fluorescence photometry. [Ca2+]i was increased by Ang II via AT1 receptors in a dose-dependent manner (EC50 = 2.4 x 10(-8) mol/l) involving two distinct phases, an initial Ca2+ peak and a sustained elevated plateau phase. The initial Ca2+ peak occurred transiently and independently of the duration of Ang II application. While the magnitude of the transient Ca2+ peak did not differ in a nominally Ca(2+)-free (3 mmol/l EGTA) solution, the Ang II-mediated sustained plateau phase of [Ca2+]i was dependent on extracellular Ca2+. Thus, the initial transient Ca2+ peak appears to arise from intracellular Ca2+ stores, whereas the plateau phase involves an external Ca2+ influx. Since collagen synthesis of cardiac fibroblasts is maximally stimulated by Ang II or by fetal bovine serum (FBS), the effects of Ang II and FBS on [Ca2+]i were compared. The magnitude of the transient Ca2+ peak induced by 10(-7) mol/l Ang II was comparable to that of 10% FBS indicating that the rise in [Ca2+]i might be involved in the signal transduction pathway of Ang II-mediated collagen synthesis of cardiac fibroblasts.

Rheumatic manifestations of scurvy. A report of two cases.

Bleeding into the muscles and joints can be the presenting manifestation of scurvy, as illustrated by two case-reports. One patient presented with hemarthrosis of the tibiotalar joint due to an insufficiency fracture and was suspected to have scurvy based on the presence of purpura and hypertrophy of the gums with loss of teeth. In the other patient, multiple hematomas in the lower limbs were found at presentation and the presence of coiled hairs suggested the diagnosis. Both patients had completely eliminated fruit and vegetables from their diet. Low levels of ascorbic acid were found in serum and urine. A full recovery was achieved in both cases under ascorbic acid supplementation.

[Spironolactone: renaissance of anti-aldosterone therapy in heart failure?]. / Spironolacton: Renaissance der Antialdosterontherapie bei Herzinsuffizienz?

Mortality of patients with severe congestive heart failure (CHF) is still high despite combined treatment with angiotensin-converting enzyme (ACE) inhibitors, diuretics, and digitalis. Further therapeutic regimens are needed which include reversal of adverse myocardial remodeling and subsequent ventricular dysfunction. One third of all patients with CHF have diastolic left ventricular (LV) dysfunction with preserved systolic function. In these patients myocardial collagen matrix is the major determinant of myocardial stiffness and therefore diastolic function. Cardiac fibroblasts, expressing mRNA for types I and III collagens which are the major fibrillar proteins of the myocardial collagen network and for matrix metalloproteinase (MMP) 1 which is the key enzyme for interstitial collagen degradation, are controlled by the renin-angiotensin-aldosterone (RAAS) system irrespective of hemodynamics and cardiac myocyte growth. In the rat with primary or secondary hyperaldosteronism, myocardial fibrosis occurs in the pressure overloaded, hypertrophied left and in the normotensive, nonhypertrophic right ventricle. In contrast, no fibrosis is found in either ventricle of rats with infrarenal aortic banding, when the RAAS is not activated, despite comparable systemic hypertension and LV hypertrophy. In cultured cardiac fibroblasts, either effector hormone of the RAAS, angiotensin (Ang) II and aldosterone (Aldo) stimulate collagen synthesis measured by 3H-proline incorporation under serum-free conditions. Aldo is able to stimulate collagen synthesis normalized per total protein synthesis in a dose-dependent manner and at concentrations (10(-9) M) which are comparable to stimulated states in vivo (e.g., CHF). While Aldo does not affect collagen degradation AngII significantly inhibits, MMP 1 activity that would lead to further accumulation of collagen in the myocardium. Specific AngII type I or Aldo receptor antagonists are able to abolish the AngII or Aldo-mediated increase in collagen synthesis, respectively. In vivo in rats with primary or secondary hyperaldosteronism, the Aldo antagonist spironolactone has been shown to prevent myocardial fibrosis in both ventricles irrespective of the development of LV hypertrophy and hypertension. Thus, in vivo and in vitro evidence could be provided that the mineralocorticoid. Aldo, plays a pivotal role in promoting myocardial fibrosis and can be antagonized by its competitive receptor blocker, spironolactone. This may be of particular clinical relevance in treating patients with CHF where the RAAS is activated leading to myocardial fibrosis with subsequent deterioration of myocardial function. Clinical trials are needed to confirm these experimental data. If the ongoing RALES mortality study will prove that survival and/or morbidity of patients with CHF are improved by combined ACE inhibitor/spironolactone treatment a renaissance of anti-aldosterone therapy in patients with CHF would occur.

The first twelve cases of computer assisted periacetabular osteotomy.

Image guided freehand navigation of surgical instruments has been applied to the Bernese periacetabular osteotomy, a complex surgical technique for the treatment of dysplastic hips. This navigation system has been introduced into the operating room and has so far been used for 12 patients. Image data from computed tomography (CT) scans are presented in various ways to support the preoperative plan and to provide optimized control of surgical action. Special attention has been paid to the implementation of a sophisticated surgeon-machine interface. This paper describes the features of this novel surgical navigation system and its introduction into the clinical environment.

Man-machine interfaces in computer assisted surgery.

The clinical potential of computer assisted surgery (CAS) has been more and more widely acknowledged since CAS systems have been introduced into the operating room (OR) theater. Especially the improvements in safety and accuracy are remarkable and strengthen the ties between surgeons and engineers. Tumor stereotaxis was introduced to neurological surgery in the early 1980s, and currently systems with and without robotic navigation are in use for specific medical indications. Recently, solutions for computer assisted orthopedic surgery were developed and applied to various anatomical regions. However, with the establishment of CAS in vivo, a new complex of problems, which was not present in the laboratory setup, was introduced: the man-machine interface. Currently, the complexity of available CAS systems requires the presence of at least one system engineer (often called the "operator") in the OR. As a consequence, there is no possibility for direct communication between the surgeon and the machine or software. Most of the program steps involved in CAS and choices to be made intraoperatively have to be transferred to the software by means of communication of the surgeon with the operator. Particularly, the establishment of a relation between the virtual object (i.e., a medical image) and the surgical object (i.e., the patient), often denoted as "matching" or "skeletal registration," requires intensive interaction of the surgeon with the computer. A literature survey revealed that no CAS system in clinical use exists without a system engineer or a comparable person, and our clinical experience indicated that the matching process is a weak point in most systems. Because it appears to be contradictory to cost-reduction efforts in health care to have a highly paid specialist in the OR, this research evaluates strategies to facilitate the man-machine interface with the final goal of establishing a direct control of the system by the surgeon or the medical personnel traditionally present at surgery. Options to be investigated include 1) a CAS control panel (virtual keyboard) as an integrated component of the existing navigation system and 2) introduction of a commercial voice-recognition system. The implementation of these strategies into the existing CAS setup at the Department of Orthopaedic Surgery at the Inselspital (University of Bern) and clinical experience gained are reported.

Renin-angiotensin system and myocardial collagen matrix: modulation of cardiac fibroblast function by angiotensin II type 1 receptor antagonism.

BACKGROUND: Left ventricular hypertrophy is an adaptive process to increased loading of the left ventricle. This condition becomes pathologic with impaired myocardial function if the various tissue compartments of the myocardium (myocyte, interstitial and vascular compartments) are inhomogeneously altered, particularly if myocardial fibrosis occurs. In arterial hypertension, myocardial fibrosis is known to occur in association with activated circulating or local renin-angiotensin systems and includes reactive perivascular and interstitial fibrosis in both the pressure-overloaded hypertrophied left ventricle and the normotensive non-hypertrophied right ventricle. Therefore, it appears that hemodynamics are not primarily responsible for the adverse myocardial collagen matrix remodeling in hypertensive heart disease. Accordingly, we studied the interaction between cultured adult rat cardiac fibroblasts, which express messenger (m)RNAs for types I and III collagens, the major fibrillar collagens in the heart, and angiotensin II (Ang II), the effector hormone of the renin-angiotensin system. OBJECTIVES: Specifically, we sought to determine whether Ang II stimulates total collagen synthesis and the expression of type I collagen mRNA in cultured adult rat cardiac fibroblasts, and to investigate the effects of Ang II on intracellular Ca2+ levels. MATERIALS AND METHODS: Adult rat cardiac fibroblasts were cultured in Dulbecco's Modified Eagle's Medium + 10% fetal calf serum and incubated for 24 h with Ang II with or without specific Ang II type 1 or type 2 receptor antagonists. Collagen synthesis was measured using a 3H-proline incorporation assay, and type I collagen mRNA was determined using reverse-transcriptase polymerase chain reaction. Intracellular Ca2+ transients were measured by fast fluorescence photometry using the fluorescent dye fura-2-acetoxymethylester. RESULTS: We found a 76% increase in type I collagen mRNA in cultured cardiac fibroblasts after a 24-h incubation with Ang II, and this was abolished by simultaneous incubation with the Ang II type 1 (AT1)-receptor antagonist candesartan. Likewise, total collagen synthesis was stimulated by Ang II in a dose-dependent manner, and this stimulation was also counteracted by candesartan. Additionally, incubation with Ang II resulted in a significant dose-dependent increase in intracellular Ca2+ transients which was also abolished by treatment with candesartan. CONCLUSIONS: Ang II stimulates collagen synthesis in cultured adult rat cardiac fibroblasts via AT1 receptors, most likely using Ca2+ as a second messenger. These findings suggest a direct interaction between Ang II and cardiac fibroblasts in mediating myocardial fibrosis in arterial hypertension, leading to pathologic left ventricular hypertrophy with initially impaired diastolic and ultimately reduced systolic function of the left ventricle. The AT1-receptor antagonist candesartan cilexetil, which is the prodrug of the active compound candesartan, may prove valuable in preventing or regressing myocardial fibrosis in hypertensive heart disease.

Development and implementation of a quality assurance program for mammography.

As a pilot study for a national campaign to promote the use of screening mammography, the Virginia Division of the American Cancer Society conducted a breast cancer awareness project with mammography screening. An important part of the program was the development of a quality assurance program for mammography. Guidelines were established for equipment, image recorders, processing, dose, and patient positioning. A survey of information about the mammographic equipment was conducted, and the mammograms from each facility were reviewed. A total of 63 mammographic units in 56 facilities statewide were included in the month-long program during which approximately 9,000 women were screened.