[Non-cystic fibrosis bronchiectasis: diagnosis and treatment]. / Non-CF-Bronchiektasen: Diagnostik und Therapie.

Bronchiectasis is the term used for irreversibly dilated airways. Exact epidemiological information on the frequency of bronchiectasis is not available, but the morphological findings are increasingly detected and the associated syndrome is more frequently diagnosed due to improved imaging techniques and increased awareness among chest physicians. The workup of these patients includes a wide panel of investigations guided by patient history and clinical presentation. Despite thorough evaluation the aetiology frequently remains unclear. Chronic infection with Pseudomonas aeruginosa is associated with a severe course of the disease and its detection has impacts on the therapeutic management. Chest physiotherapy, mucoactive substances and antibiotics are the mainstay of therapy. In this review the evaluation of bronchiectasis and the recent therapeutic insights for non-cystic fibrosis bronchiectasis are discussed.

[Rheumatoid arthritis and interstitial lung alterations - a clear case, isn't it?]. / Rheumatoide Arthritis und interstitielle Lungenver-änderungen - Ein klarer Fall! Oder eben doch nicht?

In a patient with rheumatoid arthritis (RA) and asymptomatic, diffuse reticulo-nodular lung parenchymal alterations with upper lobe predominance, a Caplan syndrome (CS) was diagnosed. According to the size of the pulmonary nodules, classification into two subtypes of the CS has been proposed: the classic (Caplan) type and the silicotic type. Patients with CS often present with considerable x-ray or computertomographic changes but relatively few symptoms. However, in case of respiratory symptoms, infectious complications or pneumotoxic side effects of the immunsuppressive/immune-modulating pharmacotherapy for RA must be encountered in the differential diagnosis.

Effectiveness of a procalcitonin algorithm to guide antibiotic therapy in respiratory tract infections outside of study conditions: a post-study survey.

All published evidence on procalcitonin (PCT)-guided antibiotic therapy was obtained in trials where physicians knew that they were being monitored, possibly resulting in higher adherence to the PCT algorithm. This study investigates the effectiveness of PCT guidance in an observational quality control survey. We monitored antibiotic therapy and algorithm adherence in consecutive patients with respiratory tract infections admitted to the Kantonsspital Aarau, Switzerland, between May 2008 and February 2009. The results were compared to the site-specific results of the former ProHOSP study. Overall and more pronounced for patients with community-acquired pneumonia, the median duration of antibiotic treatment in this survey was shorter than the ProHOSP control patients (6 vs. 7 days, P = 0.048 and 7 vs. 9 days, P < 0.001). In 72.5% of patients, antibiotics were administered according to the prespecified PCT algorithm. No significant differences concerning adverse medical outcome could be detected. This study mirrors the use of PCT-guided antibiotic therapy in clinical practice, outside of trial conditions. If algorithm adherence is reinforced, antibiotic exposure can be markedly reduced with subsequent reduction of antibiotic-associated side effects and antibiotic resistance. The integration of the PCT algorithm into daily practice requires ongoing reinforcement and involves a learning process of the prescribing physicians.

[Scepticism is warranted or when the CT scan reveals to be a pitfall]. / Gesunde Skepsis tut Not oder: wenn das Spiral-CT in falscher Sicherheit wiegt....

We report the case of a 72-year old woman with known metastatic breast cancer who presented to the emergency department with progressive dyspnea on exertion and chest pain. The diagnosis of pulmonary embolism could be established by pulmonary scintigraphy after computed tomography and ultrasound of the lower extremities had been negative in spite of a moderate clinical pretest probability (Wells score). This case shows that even if we manage suspected pulmonary embolism using algorithms combining clinical probability, computed tomography and ultrasound we must remain aware of eventually missing the diagnosis and carry on investigating cases with elevated clinical probability.

[Pulmonary nodules in a patient on long-term steroid treatment]. / Pulmonale Rundherde unter Steroid-Dauertherapie.

We report on a patient who was chronically treated with steroids. She simultaneously developed pulmonary nocardiosis as well as a soft tissue infection and osteomyelitis by mycobacterium abscessus. Both infections are rare, but more frequently occur in immunocompromised hosts. The patient was healed after 12 month of adequate antibiotic treatment.

Prediction of hypertensive crisis based on average, variability and approximate entropy of 24-h ambulatory blood pressure monitoring.

Approximate entropy (ApEn) of blood pressure (BP) can be easily measured based on software analysing 24-h ambulatory BP monitoring (ABPM), but the clinical value of this measure is unknown. In a prospective study we investigated whether ApEn of BP predicts, in addition to average and variability of BP, the risk of hypertensive crisis. In 57 patients with known hypertension we measured ApEn, average and variability of systolic and diastolic BP based on 24-h ABPM. Eight of these fifty-seven patients developed hypertensive crisis during follow-up (mean follow-up duration 726 days). In bivariate regression analysis, ApEn of systolic BP (P<0.01), average of systolic BP (P=0.02) and average of diastolic BP (P=0.03) were significant predictors of hypertensive crisis. The incidence rate ratio of hypertensive crisis was 14.0 (95% confidence interval (CI) 1.8, 631.5; P<0.01) for high ApEn of systolic BP as compared to low values. In multivariable regression analysis, ApEn of systolic (P=0.01) and average of diastolic BP (P<0.01) were independent predictors of hypertensive crisis. A combination of these two measures had a positive predictive value of 75%, and a negative predictive value of 91%, respectively. ApEn, combined with other measures of 24-h ABPM, is a potentially powerful predictor of hypertensive crisis. If confirmed in independent samples, these findings have major clinical implications since measures predicting the risk of hypertensive crisis define patients requiring intensive follow-up and intensified therapy.

[Long-term follow up after antithyroid drug treatment in Graves' disease]. / Langzeitverlauf nach thyreostatischer Therapie bei Basedow-Hyperthyreose.

BACKGROUND AND OBJECTIVE: In Europe antithyroid drug (ATD) therapy is the preferred initial treatment for patients with a first episode of Graves' disease. Results of long-term recurrence rates following ATD therapy are conflicting. The main goal was to assess long-term recurrence rate after ATD treatment. Secondarily we tried to verify chemical and clinical findings (thyrotropin receptor antibodies (TRAb), duration of primary treatment, age and goitre size) as predictive factors. PATIENTS AND METHODS: Records of 94 patients with a first episode of Graves' disease (1990-1995) treated by ATD were retrospectively analyzed. 18 patients were lost for follow up investigations, the remaining 76 (65 women, 11 men, age 16-76 years) patients were followed for 99 (+/- 22) months (mean +/- SD). To verify the predictive factors a logistic regression analysis was done. RESULTS: Among the 76 patients 16 underwent near-total resection (n = 5) or radioiodine therapy (n = 11) after initial ATD treatment. Sixty patients were treated during 19 +/- 16 months (mean +/- SD) with ATDs and were euthyroid when treatment was stopped. Thirteen of the 60 patients (21.7%) remained in remission after discontinuation of ATD therapy, in 42 patients (70%) hyperthyroidism recurred, in four patients (6.7%) ATD could not be stopped, one patient (1.7%) had a persistent hypothyroidism after discontinuation of ATD. Relapse rate was inversely correlated with duration of primary ATD treatment (p < 0.05), but not with TRAb titer at the time of diagnosis nor at the time of ATD discontinuation. Also, no correlation could be noticed with goitre size at the time of diagnosis. An inverse correlation of the age at the time of diagnosis with relapse rate was of only borderline significance (p = 0.055). CONCLUSIONS: Initial successful treatment with ATD is followed by a high recurrence rate in our population. Two possible negative predictors of relapse are short duration of primary ATD treatment and young age at the time of diagnosis. TRAb titer at the time of diagnosis or at the time of ATD discontinuation and goitre size seem to have no influence on the outcome.

[Endocrine crises]. / Endokrine Krisen.

Pituitary apoplexy, diabetes insipidus, thyroid storm, myxedema coma, parathyrotoxic crisis, hypocalcemia tetany, pheochromocytoma and Addison crisis, diabetic ketoacidosis, diabetic hyperosmolar nonketotic coma, hypoglycemia and carcinoid crisis are the most important endocrine crises. Some of them are common, others very rare. All physicians nevertheless need to have at least a basic knowledge of all of them, since symptoms and signs of endocrine crises overlap with those of other severe disease states, and the failure to recognise endocrine crises as such and to begin rapidly the specific therapy can have fatal consequences.

[Nasal polyps and osteolyses]. / Nasenpolypen und Osteolysen.

A 38-year-old man presented with a 2-month history of progressive leg pain. An x-ray film of both tibial bones showed multiple osteolysis. At the same time, nasal polyps were present. A biopsy of the tibial bone remained unclear. A carcinoma was not found. A biopsy of the nasal polyps revealed a Rosai-Dorfman-Destombes disease.

Urinary iodine concentration during pregnancy in an area of unstable dietary iodine intake in Switzerland.

We prospectively investigated urinary iodine concentration (UIC) in pregnant women and in female, non-pregnant controls in the canton of Berne, Switzerland, in 1992. Mean UIC of pregnant women [205 +/- 151 microg iodine/g creatinine (microg l/g Cr); no. = 153] steadily decreased from the first (236 +/- 180 microg l/g Cr; no. = 31) to the third trimester (183 +/- 111 microg l/g Cr, p < 0.0001; no. = 66) and differed significantly from that of the control group (91 +/- 37 microg l/g Cr, p < 0.0001; no. = 119). UIC increased 2.6-fold from levels indicating mild iodine deficiency in controls to the first trimester, demonstrating that high UIC during early gestation does not necessarily reflect a sufficient iodine supply to the overall population. Pregnancy is accompanied by important alterations in the regulation of thyroid function and iodine metabolism. Increased renal iodine clearance during pregnancy may explain increased UIC during early gestation, whereas increased thyroidal iodine clearance as well as the iodine shift from the maternal circulation to the growing fetal-placental unit, which both tend to lower the circulating serum levels of inorganic iodide, probably are the causes of the continuous decrease of UIC over the course of pregnancy. Mean UIC in our control group, as well as in one parallel and several consecutive investigations in the same region in the 1990s, was found to be below the actually recommended threshold, indicating a new tendency towards mild to moderate iodine deficiency. As salt is the main source of dietary iodine in Switzerland, its iodine concentration was therefore increased nationwide in 1998 for the fourth time, following increases in 1922, 1965 and 1980.

Intermediate results of health related quality of life after vertical banded gastroplasty.

OBJECTIVES: The purpose of this study is to evaluate (a) health-related quality of life (HRQL) after vertical banded gastroplasty (VBG) (Mason) and (b) predictors of HRQL. SUBJECTS: Eighty-two consecutive patients were assessed preoperatively and then after 6, 12 and 24 months. Patients filled out questionnaires for subjective appraisal of HRQL (physical well-being, mood, physical performance, perceived health, social support and coping/adjustment). RESULTS: The greatest improvement in weight and HRQL was seen within 6 months of surgery. Twenty-four months after VBG weight reduction (P<0.05), perceived health (P<0.05), physical well-being (P<0.05), physical performance (P<0.05), mood (P<0.05), coping/adjustment (P<0.05) continued to be better than before surgery. Preoperative binge eating was the most important predictor of HRQL. CONCLUSION: Two years after VBG weight loss and a significant improvement of HRQL can be found. HRQL and weight loss are not associated in terms of outcome, indicating that weight loss alone may not be enough to improve HRQL.

Nuclear localization of epidermal growth factor and epidermal growth factor receptors in human thyroid tissues.

Epidermal growth factor (EGF) has widespread growth effects, and in some tissues proliferation is associated with the nuclear localization of EGF and epidermal growth factor receptor (EGFR). In the thyroid, EGF promotes growth but differs from thyrotropin (TSH) in inhibiting rather than stimulating functional parameters. We have therefore studied the occurrence and cellular distribution of EGF and EGFR in normal thyroid, in Graves' disease, where growth is mediated through the thyrotropin receptor (TSHR), and in a variety of human thyroid tumors. In the normal gland the staining was variable, but largely cytoplasmic, for both EGF and EGFR. In Graves' disease there was strong cytoplasmic staining for both EGF and EGFR, with frequent positive nuclei. Nuclear positivity for EGF and particularly for EGFR was also a feature of both follicular adenomas and follicular carcinomas. Interestingly, nuclear staining was almost absent in papillary carcinomas. These findings document for the first time the presence of nuclear EGF and EGFR in thyroid. Their predominant occurrence in tissues with increased growth (Graves' disease, follicular adenoma, and carcinoma) may indicate that nuclear EGF and EGFR play a role in growth regulation in these conditions. The absence of nuclear EGF and EGFR in papillary carcinomas would suggest that the role played by EGF in growth control differs between papillary carcinoma and follicular adenomas/carcinomas of the thyroid.

Graves' ophthalmopathy: natural history and treatment outcomes.

BACKGROUND: The pathogenesis of Graves' ophthalmopathy has not been yet clarified, and from a therapeutic standpoint Graves' ophthalmopathy remains an enigma. The natural course and effects of different treatment regimens are poorly documented. RESULTS: The mean observation period was 3.23 years (1-8.9 years) for all 196 patients, and 2.85 years (1-8.9 years) for the 81 patients with Graves' ophthalmopathy. The gender distribution was 77% female and 23% male in patients with Graves' disease and ophthalmopathy, and 81% female and 19% male in those patients without ophthalmopathy (p = 0.57). Seventy per cent of the patients developed Graves' ophthalmopathy within 12 months before or after the onset of the hyperthyroidism. Among the 81 patients with ophthalmopathy 53 (65%) received no therapy or only local protective agents. Twenty-five of these patients improved substantially, 26 did not change, and 2 deteriorated progressively. These results were independent of the severity of the EO (p = 0.42). Among the 11 patients initially treated with systemic corticosteroids 7 improved, 3 did not change, and 1 worsened. Five patients received initially orbital irradiation. Three improved and 2 did not change after radiotherapy. Orbital decompression was performed in 3 patients. Nine patients received a combination treatment. CONCLUSION: In conclusion, our study of a relatively large patient sample revealed the known epidemiological facts regarding Graves' disease and endocrine ophthalmopathy. The majority of patients needed no therapy or only local protective agents, and 47% improved spontaneously. Systemic corticosteroids and orbital irradiation appear to be equally effective as initial treatment in patients with more severe forms of Graves' ophthalmopathy.

[Calculating the basal metabolic rate and severe and morbid obesity]. / Berechnung des Grundumsatzes bei schwerer und morbider Adipositas.

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the currently available predictive equations for basal metabolic rate (BMR) in subjects with obesity class II and III, and to assess the contribution by the components of a two-compartment model of body composition, namely the lean body mass (LBM) and the fat mass (FM) to the prediction. A second objective was to examine the reliability of the Harris Benedict equation in obese subjects, especially with a weight > or = 120 kg. PATIENTS AND METHODS: In 43 patients (age range 18 to 61 years, 5 men, 38 women) with obesity class II and III (body mass index, BMI, mean +/- SD 45.6 kg/m2 +/- 5.4 kg/m2, range 37.1-58.6 kg/m2) basal metabolic rate BMR was determined using indirect calorimetry (Deltatrac MBM, Datex, Instrumentarium Corp., Helsinki, Finnland) and the components of body composition were determined using the bioelectrical-impedance-analysis (BIA) method (BIA, Akern-Gerät, RJL Systems, Detroit). Calculated BMR was compared with measured BMR. RESULTS: The best fitting equations for predicting BMR in these 43 severe und morbidly obese subjects were the Harris-Benedict (ratio calculated BMR to measured, BMR mean +/- SD%; correlation coefficient r = 101 +/- 12.9; 0.69), the Jensen (101.5 +/- 12.3; 0.74), the Nelson (99.3 +/- 11.4; 0.76) and the Cunningham equation (98.9 +/- 11.7; 0.74). The predictive value of the original Harris-Benedict equation was slightly different from modified Harris-Benedict equation, which was recalculated by Roza et al. (101.1 +/- 12.9; 0.69 vs. 99.7 +/- 12.8; 0.69). In the group of the 22 subjects with a body weight > or = 120 kg ratio of estimated values for BMR using original Harris-Benedict equation to measured BMR was 102.2 +/- 15.4% (mean +/- SD%, r = 0.61), respectively 93.2 +/- 14.5% (r = 0.50) when weight was set at 120 kg due to current recommendations. The ratio calculated BMR/measured BMR according to the Nelson equation in this subgroup was 101.0 (12.1/0.74). CONCLUSION: In patients with obesity class II and III the equation of Harris-Benedict predicted the average BMR with acceptable precision for clinical use and was better fitting than most of the currently available predictive equations for basal metabolic rate (BMR). However, the recalculated version (by Roza et al.) was more accurate and should therefore be used instead of the original equation: BMR (men) = 88.362 + 4.799 x (length) + 13.397 x (weight) - 5.677 x (age); BMR (women) = 447.593 + 3.098 x (length) + 9.247 x (weight) - 4.330 x (age). The Nelson equation, including not only LBM but FM as additional predictor, was the best predicting equation ([108 LBM + 16.9 FM]0.239). Harris-Benedict equation had sufficient precision also in extreme obese subjects with a body weight > or = 120 kg, so there is no need for adaptation.

[Clinical management of acute head injury]. / Klinisches Management des akut Hirnverletzten.

Patients after acute head injury are susceptible to secondary insults and therefore to secondary brain injury. A comprehensive approach, starting at the site of the accident, followed by emergency diagnosis and treatment in the appropriate emergency department of the trauma centre, intensive care and specific neurorehabilitation is the only way to minimise sequelae of primary brain lesions, prevent secondary brain damage and establish optimum frame conditions with respect to recovery from non-definite brain damage.

Growth hormone regulates growth hormone receptor gene transcription in primary human thyroid cells.

In this study the regulation of GH-receptor gene (GHR/GHBP) transcription by different concentrations of GH (0, 12.5, 25, 50, 150, 500 ng/ml) with and without variable TSH concentrations (0.5, 2, 20 mU/l) in primary human thyroid cells cultured in serum-free hormonally-defined medium was studied. The incubation time was 6 h and GHR/GHBP mRNA expression was quantitatively assessed by using PCR amplification at hourly intervals. Correlating with the GH-concentrations added a constant and significant increase of GHR/GHBP gene transcription was found. After the addition of 12.5 ng/ml GH, GHR/GHBP mRNA concentration remained constant over the incubation period of 6 h but in comparison with the experiments where no GH was added there was a significant change of GHR/GHBP mRNA expression. Following the addition of 25 ng/ml GH a slight but further increase of GHR/GHBP transcription products was seen which increased even more in the experiments where higher GH concentrations were used. These data focusing on GHR/GHBP gene transcription derived from cDNA synthesis and quantitative PCR amplification were confirmed by run-on experiments. Furthermore, cycloheximide did not affect these changes supporting the notion that GH stimulates GHR/GHBP gene transcription directly. In a second set of experiments, in combination with variable TSH levels, identical GH concentrations were used and no difference in either GHR/GHBP mRNA levels or in transcription rate (run-on experiments) could be found. In conclusion, we report data showing that primary thyroid cells express functional GH-receptors in which GH has a direct and dose dependent effect on the GHR/GHBP gene transcription. Furthermore, TSH does not a have a major impact on GHR/GHBP gene regulation.

[Intensive care treatment concepts after traumatic spinal cord injury]. / Intensivmedizinische Behandlungskonzepte nach traumatischer Rückenmarksverletzung.

Spinal injuries are caused by strong traumatic impacts, followed not only by a local spinal reaction but also systemic involvement. The main problems in the early posttraumatic period are haemodynamic instability, pulmonary insufficiency and SIRS. In this period multiple risks of secondary injuries to the spinal cord or other organs exist and may develop towards life-threatening sepsis, ARDS and multi-organ failure. Optimum therapy for spinal injury patients is demanding and requires an experienced team for diagnosis as well as primary and secondary care. Close cooperation between intensive care and surgery is also important.

[Mason vertical gastroplasty in treatment of morbid obesity. Results of a prospective clinical study]. / Die vertikale Gastroplastik nach Mason zur Behandlung der morbiden Adipositas. Ergebnisse einer prospektiven klinischen Studie.

Morbid obesity (body mass index > 40 kg/m2) is a risk factor for cardiovascular, pulmonary, metabolic, neoplastic, and psychologic sequelae. In the present prospective clinical study 65 patients (11 men, 54 women) underwent vertical banded gastroplasty (Mason procedure) from June 1994 to October 1997. The median age was 41 +/- 5.3 years (range 18-69; n = 65). Preoperative body weight was 135 +/- 23 kg (96-229; n = 65), excess body weight in kg was 75 +/- 6.9 (44-155; n = 65) or in % 126 +/- 10 (78-223; n = 65) and BMI was 49 +/- 7.4 kg/m2 (39-69; n = 65). Mean hospital stay was 9.7 +/- 2.4 days (6-18; n = 65). Hospital mortality was 0% (0/65). Early complications were vomiting (30%) and problems in wound healing (15%; n = 65). Late complications (> 30 days) were incisional hernias (13.8%) and staple-line disruptions (12.3%; n = 65) with a reoperation rate of 23% (15/65). Median follow-up was 15.0 +/- 5.2 months (2-42) with a follow up rate of 100%. Mean weight loss after 12 months was 38.5 +/- 17 kg (30-98; n = 34) (P < 0.0001) and loss of excessive body weight 65 +/- 10% (57-86; n = 34), respectively (P < 0.0001). Cardiovascular risk factors (hypertension, diabetes, hyperlipidemia) were significantly improved within 12 months (n = 34). Vertical banded gastroplasty (Mason procedure)--well established for 20 years--is a good, safe therapy for morbid obesity if strict indications for operation are observed and if there is multidisciplinary long-term follow-up. Comorbid risk factors are considerably reduced and a long-term weight loss of more than 50% can be achieved without the risk of pathological metabolic changes.

Follicle-forming cat thyroid cell lines synthesizing extracellular matrix and basal membrane components: a new tool for the study of thyroidal morphogenesis.

Interactions between follicular epithelial cells and extracellular matrix (ECM) are supposed to play an important role in the development and maintenance of thyroid tissue architecture. In the present study we have therefore investigated the synthesis of ECM components by a feline thyroid cell line which is able to form follicle-like structures in vitro, and also in v-ras-transfected and control-transfected sublines. Transfections were performed by lipofection with pZSR (viral Harvey ras gene; neo) and pSV2-neo (control, neo only) plasmids. We have adapted a semisolid culture system composed exclusively of polymerized alginate and therefore devoid of ECM components. Feline cells embedded in alginate gels as single cells and cultured for up to 90 days formed cell clusters within 10 days. Follicle-like structures were formed in the original cell lines and also in the v-ras- and control-transfected cells. Differences in proliferation rates were observed, the v-ras-transfected cells growing up to two to three times faster than the non-transfected cells. Immunostaining was done using rabbit first antibodies directed against mouse collagen IV, human fibronectin, laminin (tumor Engelbreth-Holm-Swarm laminin), perlecan and other ECM components. For comparison, immunostaining was also performed on cryosections of nodular goiters of six hyperthyroid cats. The cell lines and their transfected clones stained strongly positive for collagen IV and fibronectin, and positively but less strongly for laminin and perlecan. The cat goiter tissue stained positively for collagen IV, laminin, perlecan, and fibronectin, and positive staining for S-laminin (containing the beta2-chain) was seen in blood vessel walls in this tissue. In conclusion, cat cell lines grow three-dimensionally in alginate beads over several weeks, they form follicle-like structures and express the same ECM components as the native cat goiter tissue. Transfection with v-ras does increase proliferation rate, but does not fundamentally alter formation of follicle-like structures and ECM expression. Alginate gel culture is a promising new tool for the study of follicular morphogenesis, polarity, the expression pattern of ECM components and of the interaction between thyrocytes and ECM. It avoids interference caused by gels composed of ECM components.