Review & meta-analysis: isopropanolic black cohosh extract iCR for menopausal symptoms - an update on the evidence.

A systematic literature search revealed 35 clinical studies and one meta-analysis comprising 43,759 women, of which 13,096 were treated with isopropanolic Cimicifuga racemosa extract (iCR). Compared to placebo, iCR was significantly superior for treating neurovegetative and psychological menopausal symptoms, with a standardized mean difference of -0.694 in favor of iCR (p < 0.0001). Effect sizes were larger when higher dosages of iCR as monotherapy or in combination with St. John's wort (Hypericum perforatum [HP]) were given (-1.020 and -0.999, respectively), suggesting a dose-dependency. For psychological symptoms, the iCR+HP combination was superior to iCR monotherapy. Efficacy of iCR was comparable to low-dose transdermal estradiol or tibolone. Yet, due to its better tolerability, iCR had a significantly better benefit-risk profile than tibolone. Treatment with iCR/iCR+HP was well tolerated with few minor adverse events, with a frequency comparable to placebo. The clinical data did not reveal any evidence of hepatotoxicity. Hormone levels remained unchanged and estrogen-sensitive tissues (e.g. breast, endometrium) were unaffected by iCR treatment. As benefits clearly outweigh risks, iCR/iCR+HP should be recommended as an evidence-based treatment option for natural climacteric symptoms. With its good safety profile in general and at estrogen-sensitive organs, iCR as a non-hormonal herbal therapy can also be used in patients with hormone-dependent diseases who suffer from iatrogenic climacteric symptoms.

Ultra-thin resin embedding method for scanning electron microscopy of individual cells on high and low aspect ratio 3D nanostructures.

The preparation of biological cells for either scanning or transmission electron microscopy requires a complex process of fixation, dehydration and drying. Critical point drying is commonly used for samples investigated with a scanning electron beam, whereas resin-infiltration is typically used for transmission electron microscopy. Critical point drying may cause cracks at the cellular surface and a sponge-like morphology of nondistinguishable intracellular compartments. Resin-infiltrated biological samples result in a solid block of resin, which can be further processed by mechanical sectioning, however that does not allow a top view examination of small cell-cell and cell-surface contacts. Here, we propose a method for removing resin excess on biological samples before effective polymerization. In this way the cells result to be embedded in an ultra-thin layer of epoxy resin. This novel method highlights in contrast to standard methods the imaging of individual cells not only on nanostructured planar surfaces but also on topologically challenging substrates with high aspect ratio three-dimensional features by scanning electron microscopy.

Comparing Nalmefene and Naltrexone in Alcohol Dependence: Are there any Differences? Results from an Indirect Meta-Analysis.

BACKGROUND: The mu-opioid antagonist naltrexone is one of the few approved pharmacotherapies for the treatment of alcohol dependence. Recently, the mu-opioid antagonist and partial kappa agonist nalmefene was approved by the European Medicines Agency for the reduction of alcohol consumption in adult patients with alcohol dependence. To date, no head-to-head studies have compared the efficacy and safety of naltrexone and nalmefene in reducing alcohol consumption. METHODS: An indirect meta-analysis of randomized controlled studies on these 2 medications was conducted. A random effects model was used to measure effects and compare the 2 medications. 4 placebo-controlled studies with nalmefene and 13 with naltrexone were included. RESULTS: A statistically significant advantage of nalmefene towards naltrexone in the 2 patient-relevant outcome efficacy criteria, quantity and frequency of drinking, was found. Both drugs had a benign safety profile. CONCLUSIONS: This indirect meta-analysis indicates an advantage of nalmefene over naltrexone. Nalmefene is an effective and well-tolerated medication for the reduction of alcohol consumption. Additional data are necessary to demonstrate possible advantages of nalmefene over naltrexone in the treatment of alcohol dependence.

Tolerability of a new fast updosed immunologically enhanced subcutaneous immunotherapy formulation with an optimized allergen to adjuvant ratio under routine practice conditions: a noninterventional observational study.

BACKGROUND AND OBJECTIVES: A fast updosed immunologically enhanced subcutaneous immunotherapy (SCIT) formulation with an optimized allergen to aluminium hydroxide ratio was first introduced in September 2009 in Germany. A large randomized controlled trial showed that the formulation had considerable immunologic effects and good tolerability. In this open-label, uncontrolled, noninterventional study, tolerability was investigated during routine application. PATIENTS AND METHODS: Patients with allergic rhinoconjunctivitis and/or asthma were treated with pollen and mite allergens using a 5-injection updosing schedule (AVANZ: 300, 600, 3000, 6000 and 15 000 SQ+ units) with weekly intervals, followed by a maintenance schedule with injections of 15,000 SQ+ units.Adverse events (AEs) were recorded by physicians, and symptoms and use of symptomatic medication were analyzed before the start of therapy and after an average 8-month treatment period. RESULTS: SCIT was documented by 362 allergists in 1036 patients between September 2009 and February 2011. AEs mainly consisted of local reactions during updosing (in 24.5% of patients). Systemic reactions were observed during updosing (8.4%) and maintenance therapy (1.7%), the most frequent of which was dyspnea. Overall, tolerability and the effect of treatment were rated as good or very good by 94.9% and 86.6% of patients and by 96.2% and 89.6% of physicians, respectively. CONCLUSIONS: In this open-label, noninterventional study, fast updosed immunologically enhanced SCIT (AVANZ) was well tolerated in a large group of patients.

Identifying patients with axial spondyloarthritis in primary care: how useful are items indicative of inflammatory back pain?

BACKGROUND: The value of clinical items defining inflammatory back pain to identify patients with axial spondyloarthritis (SpA) in primary care is unclear. OBJECTIVE: To identify predictive clinical parameters for a diagnosis of axial SpA in patients with chronic back pain presenting in primary care. METHODS: Consecutive patients aged < 45 years (n=950) with back pain for > 2 months who presented to orthopaedic surgeons (n=143) were randomised based on four key questions for referral to rheumatologists (n=36) for diagnosis. RESULTS: The rheumatologists saw 322 representative patients (mean age 36 years, 50% female, median duration of back pain 30 months). 113 patients (35%) were diagnosed as axial SpA (62% HLA B27+), 47 (15%) as ankylosing spondylitis (AS) and 66 (21%) as axial non-radiographic SpA (nrSpA). Age at onset ≤ 35 years, improvement by exercise, improvement with non-steroidal anti-inflammatory drugs, waking up in the second half of the night and alternating buttock pain were identified as most relevant for diagnosing axial SpA by multiple regression analysis. Differences between AS and nrSpA were detected. No single item was predictive, but ≥ 3 items proved useful for good sensitivity and specificity by receiver operating characteristic modelling. CONCLUSION: This study shows that a preselection in primary care of patients with back pain based on a combination of clinical items is useful to facilitate the diagnosis of axial SpA.

Factors associated with response in depressed elderly outpatients treated with escitalopram in a naturalistic setting in Germany.

BACKGROUND: An open, multi-centre study was designed to address the effectiveness and tolerability profile of treatment with escitalopram under naturalistic conditions, in elderly outpatients (above 65 years of age) with depression. PATIENTS AND METHODS: A total of 2 050 patients completed 8 weeks of treatment with escitalopram. Rating scales included a short version of the Montgomery-Asberg Depression Rating Scale (svMADRS), the Clinical Global Impression - Severity scale (CGI-S), and the Clinical Global Impression -Improvement scale (CGI-I) for the assessment of various clinical parameters. RESULTS: Most patients improved in their general state of health and showed a decrease in the severity of their depression. The majority (82.7%) of patients received initially 10 mg/day escitalopram. The mean svMADRS total score decreased from 31.9+/-7.9 at baseline to 14.2+/-8.5 at week 8. On completion, 63.9% of the patients were responders (> or =50% decrease of svMADRS total score from baseline) and 48.6% were remitters (svMADRS total score < or =12 at week 8). Statistically significantly more patients aged between 66 and 75 years responded to treatment and achieved remission than those aged >75 years. Logistic regression, using stepwise backward elimination, was used to model response to treatment. Statistically significant positive factors were having a current episode < or =1 month and duration of illness < or =1 year. Significant negative factors were being male, being older than 75 years, and having need of further psychotropic medication. Compared to patients diagnosed with unspecified dementia with other symptoms being predominantly depressive (F03, according to ICD-10), the response to escitalopram was significantly better for patients with depressive episodes (F32) or recurrent depressive episodes (F33), but significantly worse for patients with affective disorder (F31 or F34). The differences versus affective disorders were significant, while those for depressive episodes and recurrent depressive episodes vs. affective disorders were not significant. CONCLUSION: This observational study corroborates the effectiveness and tolerability of escitalopram treatment for elderly patients in a naturalistic treatment setting.

Efficacy and tolerance of an oral enzyme combination in painful osteoarthritis of the hip. A double-blind, randomised study comparing oral enzymes with non-steroidal anti-inflammatory drugs.

OBJECTIVE: The objective of this study was to establish the non-inferiority of an oral enzyme therapy (Phlogenzym-(PE)) as compared to the non-steroidal anti-inflammatory drug (NSAID) diclofenac (DC) in patients with osteoarthritis (OA) of the hip. METHODS: Ninety patients presenting with painful episodes of OA of the hip were treated for 6 weeks in one study centre in a phase III, randomised, double blind, parallel group trial. Altogether, 45 patients were treated in the PE group and 45 patients were treated in the DC group. Primary efficacy criteria were: WOMAC dimensions pain, joint stiffness and function, and Lequesne index as multiple endpoint according to O'Brien. The efficacy criteria were analysed applying the test of non-inferiority with regard to mean changes and frequencies, t-test, U test, ANCOVA and descriptive methods. RESULTS: Within the 6 weeks observation period, the adjusted changes from baseline to endpoint of the target parameters worked out as follows (adjusted differences, mean +/- SEM): WOMAC subscale pain (PE -10.3 +/- 1.2, DC -9.5 +/- 1.2), WOMAC subscale joint stiffness (PE -3.9 +/- 0.5, DC -3.6 +/- 0.5), WOMAC subscale physical function (PE -31.7 +/- 3.5, DC -29.7 +/- 3.5), Lequesne's index (PE -2.89 +/- 0.47, DC -2.27 +/- 0.47). Non-inferiority of PE as compared to DC with regard to the O'Brien's global sum of the standardised adjusted changes from baseline to endpoint in pain, stiffness, physical function, and Lequesne's index was established with p = 0.0025. PE was simultaneously non-inferior as compared to DC with regard to the 4 single endpoints: WOMAC subscale pain (p = 0.0033), WOMAC subscale joint stiffness (p = 0.0061), WOMAC subscale physical function (p = 0.0039), Lequesne's index (p = 0.0008) (closed test procedure). The equivalence tests remained insignificant due to comparatively lower effects of DC. For 71.1% of the PE patients and for 61.4% of the DC patients rates of good or very good global investigator assessments of efficacy were calculated (test of non-inferiority: p = 0.0011). In the majority of patients, tolerability was judged in both drug groups as very good or good. CONCLUSION: This trial showed significant non-inferiority from 6 weeks treatment with PE in patients with OA of the hip with regard to the WOMAC dimensions pain, stiffness and physical function, to Lequesne's index, to the investigator and patients assessments of efficacy, and to the responder rates based on pain, physical function, and patient assessment of efficacy. With regard to drug tolerability some tendencies in favour of PE were detected. However, in this study there was no real difference between PE and DC 100 mg/day, implying an equal benefit-risk relation between the substances. PE may well be recommended for the treatment of patients with osteoarthritis of the hip with signs of inflammation as indicated by a high pain level.

Quality of life is improved in breast cancer patients by Standardised Mistletoe Extract PS76A2 during chemotherapy and follow-up: a randomised, placebo-controlled, double-blind, multicentre clinical trial.

The objective of this randomised, multicentre, double-blind clinical trial was to investigate the impact of PS76A2, an aqueous mistletoe extract standardised to mistletoe lectins, on quality of life (QoL) in breast cancer patients. A total of 352 patients were randomly allocated to 2 groups receiving PS76A2 (15 ng mistletoe lectin/0.5 ml) or matching placebo twice weekly for 4 to 6 cycles of CMF (cyclophosphamide, methotrexate, fluorouracil) chemotherapy followed by 2 months follow-up. The primary efficacy end-point was the change from baseline of 3 FACT-G subscales (physical, emotional and functional well-being) during the fourth CMF cycle. Secondary measures included GLQ-8 (8 linear analogue self-assessment scales), Spitzer's uniscale and haematological variables. The main variables of safety analysis were adverse events, including injection site reactions and clinical laboratory tests. The results showed that physical, emotional and functional well-being improved upon PS76A2, but deteriorated following placebo. The treatment differences were statistically significant for the 3 subscales as well as for the summary score FACT-G, which was analysed as O'Brien's rank sum of its 3 subscales: The total score increased by 4.40 +/- 11.28, indicating a higher QoL after PS76A2, but decreased by 5.11 +/- 11.77 with placebo (p<0.0001). The GLQ-8 sum of 8 LASA scales was analysed as a summary score of GLQ-5 (sum of item nos. 1, 5, 6, 7, 8) and GLQ-3 (sum of item nos. 2, 3, 4). GLQ-5 characterises typical aspects of QoL, while GLQ-3 consists of 3 side-effects of CMF (feeling sick, numbness or pins and needles, loss of hair). GLQ-5 decreased by 42.9 +/- 125.0 upon PS76A2, indicating an improvement in QoL, but increased by 60.3 +/- 94.0 upon placebo (p<0.0001). GLQ-3 deteriorated in both groups (PS76A2: 13.9 +/- 52.4; placebo: 34.5 +/- 57.0), but the differences in favour of PS76A2 were, nevertheless, statistically significant (p=0.0007). The total score GLQ-8 improved by 28.9 +/- 154.6 after PS76A2 and deteriorated by 94.8 +/- 141.1 after placebo (p<0.0001). Spitzer's uniscale improved by 12.2 +/- 30.7 upon PS76A2 and deteriorated by 10.8 +/- 26.1 with placebo (p<0.0001). After follow-up without chemotherapy, a significant treatment difference in favour of PS76A2 was determined by means of FACT-G, GLQ-8 and Spitzer's uniscale. PS76A2 was well tolerated in this trial, with the exception of slight local reactions in 17.6% of the PS76A2 group. In conclusion, PS76A2 (15 ng mistletoe lectin/0.5 ml twice weekly) was shown to be safe and effective in improving QoL in breast cancer patients during chemotherapy and follow-up.

The effects of short-term immunotherapy using molecular standardized grass and rye allergens compared with symptomatic drug treatment on rhinoconjunctivitis symptoms, skin sensitivity, and specific nasal reactivity.

BACKGROUND: The efficacy and safety of short-term immunotherapy with molecular standardized allergens (STI) has been demonstrated by double-blind placebo-controlled clinical trials. The aim of this study was to compare STI with symptomatic drug treatment. METHODS: Forty-eight patients with rhinoconjunctivitis to grass and/or rye pollen were treated either with STI (ALK(7), n = 24) plus anti-allergic drugs or anti-allergic drugs, alone (n = 24) in a prospective, randomized study. Symptoms and use of drugs were reported in patient diaries and titrated nasal provocation and skin prick tests were performed at baseline, before, and after season. RESULTS: Median overall symptom (P = 0.022, U test) and medication scores (P = 0.003) were significantly lower in the STI group, as was the result for a simultaneous analysis of conjunctival, nasal, and bronchial symptom scores and medication (P = 0.005). Sensitivity in the nasal provocation test decreased in the STI group but not in the drug-treated group. These differences became significant directly after STI (P = 0.027) as well as after the grass pollen season (P < 0.001). Skin sensitivity did not change in the STI group but increased in the drug-treated group after season, with a significant difference between the two groups for the erythema (P < 0.001). CONCLUSIONS: STI reduces grass pollen-induced rhinoconjunctivitis symptoms and drug use, and specific nasal reactivity and skin sensitivity, more efficiently than a standard symptomatic treatment.

Efficacy and safety of a fixed combination phytomedicine in the treatment of the common cold (acute viral respiratory tract infection): results of a randomised, double blind, placebo controlled, multicentre study.

OBJECTIVE: The common cold (acute viral respiratory tract infection) is one of the most frequent diseases in man, world-wide. Clinically relevant efficacy should include early improvement of all symptoms. Results of a clinical trial of a commercially available fixed combination herbal remedy (Radix echinaceae, Radix baptisiae, Herba thujae) are reported here. The aim of this study was to verify clinical efficacy shown in recent studies under (i) good clinical practice (GCP) quality assurance and (ii) common situations at family doctors. METHODS: Patients attending one of 15 study centres (practitioners) as a result of an acute common cold were randomised to the double-blind placebo-controlled study. Three tablets of study medication were applied t.i.d. for 7 to 9 days. Patients daily documented the intensity of 18 cold symptoms, as well as the cold overall, using a 10-point scale and estimated their general well-being using the Welzel-Kohnen colour scales. Additionally, the severity of illness was assessed by the physician on days 4 and 8 (CGI-1). The main and confirmatory outcome measure was expressed as a total efficacy value. This was gauged from the z-standardised AUC values of the primary endpoints (rhinitis score, bronchitis score, CGI-1 and general well-being). Adverse events, overall tolerability, vital signs and laboratory parameters were documented. RESULTS: 263 patients were included. For safety analysis, all patients were used. 259 patients were evaluable for primary efficacy analysis (ITT). Results were confirmed analysing only the 238 valid cases (VCs). The primary efficacy parameters showed the superiority of the herbal remedy over placebo (p < 0.05). Effect size was 20.6% of the standard deviation (90% CI: 0.04-41.1%; ITT) and 23.1% (1.7-44.5%; VC). In relation to the general well-being, the effect size was 33.9% of the standard deviation (12.5-55.3%; VC). Patients who suffered from at least moderate symptom intensity at baseline showed response rates (at least 50% improvement of the global score, day 5) of 55.3% in the herbal remedy group and 27.3% in the placebo group (p = 0.017; NNT = 3.5). In the subgroup of patients who started therapy at an early phase of their cold, the efficacy of the herbal remedy was most prominent (p = 0.014 for the primary efficacy parameter). The therapeutic benefit of the herbal remedy had already occurred on day 2 and reached significance (p < 0.05) on day 4, and continued until the end of the treatment in the totdl score of symptoms, bronchitis score and rhinitis score, as well as in the patients' overall rating of the cold intensity. At that time, equal levels of improvement were reached three days earlier in the verum group than in the placebo group. In 26 patients receiving the herbal remedy and 23 patients receiving placebo, adverse events were reported. Adverse drug reactions were suspected in two patients in the verum group and in four patients in the placebo group. Serious adverse events did not occur. CONCLUSIONS: This study shows that the herbal remedy is effective and safe. The therapeutic benefit consists of a rapid onset of improvement of cold symptoms. If patients with colds are able to start the application of the herbal remedy as soon as practical after the occurrence of the initial symptoms, the benefit would be expected to increase (e.g. self-medication).

Stroke associated with coronary artery bypass surgery.

Medical records and neuroimaging studies of 30 patients with major neurologic events after coronary artery surgery were reviewed. Two thousand and twenty-nine coronary artery bypass graft operations were performed in our institution between October 15, 1985, and December 27, 1989. Of these, there were 30 documented neurologic events suggesting acute ischemic injury during the intraoperative or the postoperative period. Clinical manifestations included hemiparesis, monoparesis, aphasia, bilateral cortical dysfunction, cortical and brainstem dysfunction, and left homonymous hemianopsia. There were five deaths directly attributable to neurologic injury. Twenty-two patients had a CT scan of the head, of which 15 showed evidence of acute infarction, two suggested watershed lesions from cerebral hypoperfusion, and the remainder showed findings consistent with multiple cerebral emboli or primary intracranial occlusion. Five carotid arteriograms and one digital subtraction arteriogram of the carotids were obtained. Angiographic findings revealed two common carotid artery occlusions, one callosal marginal artery occlusion, and two cases of bilateral high-grade internal carotid stenoses. Our findings support the contention that in patients who suffer cerebral infarction associated with coronary artery bypass grafting, the main mechanism of injury is cerebral embolization rather than cerebral hypoperfusion.

Application and factor analysis of the menopause rating scale [MRS] in a post-marketing surveillance study of Climen.

OBJECTIVES: The menopause rating scale (MRS) has been developed as a modern tool for the assessment of menopausal complaints. It combines in practice excellent applicability and a good reliability, and there are normal values for the population available. For further practical evaluation, the MRS was applied in order to define the course of menopausal profiles in a large post-marketing surveillance study of a sequential oral hormone replacement therapy (HRT) preparation. MATERIALS AND METHODS: A total of 10904 pre- and postmenopausal women (median age 49 years) with menopausal symptoms who so far had not used the sequential preparation (Climen) were included in the study. Patients were admitted who were experienced with previous HRT (45.2%) or could be classified as never-users (54.8%). Users commonly switched over to Climen due to signs of androgenisation, irregular bleeding, other adverse drug effects as well as inadequate efficiency. Demographic data and medical history were recorded together with a listing of body weight, blood pressure, waist and hip circumference and any skin lesions. Following 3 and 6 months of application, the observation parameters were rechecked and data on tolerability, cycle pattern and adverse drug effects were recorded. Efficacy, tolerability, and reasons for withdrawal were documented. A total of 1801 gynaecologists took part, recruiting an average of six patients in each practice. Pre- and postmenopausal cases with a median age of 49 years were represented with similar frequency. A factorial analysis known as the varimax method was used to define the 'all-or-none' structure of the loadings in order to determine the structure of the variables and their relationship to the menopausal factors. RESULTS: The pre-treatment profile of the menopausal complaints by factor analysis splits up into four independent subscores of the MRS with the factors HOT FLUSHES, ATROPHY, psychological symptoms (PSYCHE), and somatic symptoms (SOMA). Current or ever-HRT did not alter the factorial profile of the MRS. Differences were observed in the intensity of the subscores with a tendency towards weaker symptoms following previous treatment with sequential preparations. SOMA appears to be related to increasing age, postmenopausal status, or co-morbidity requiring treatment. After six months of treatment, factorial loading of HOT FLUSHES, ATROPHY, PSYCHE and SOMA all dropped significantly. CONCLUSION: The MRS in its original ten-item profile suitably characterizes menopause-specific symptoms both with regard to profile and intensity of the symptoms. The MRS adequately monitors differentiated symptom variation with and without hormone replacement. Climen confirmed a wide spectrum of activity in all aspects of the MRS. The subscore structure of the factors remained stable during treatment. Only slight modulations were seen with marked emphasis on psychic aspects and sexual complaints.

Clinical experience with a modern low-dose oral contraceptive in almost 100,000 users.

Efficacy, cycle control, tolerance, and adverse events were studied in a clinical Phase IV study using a new progestogen, gestodene, in an amount of 75 micrograms combined with 30 micrograms ethinylestradiol. The study was performed as a multicenter trial in 96,000 patients over a period of 6 cycles. Half of the patients taking the new preparation were first-time OC users, the other half switched from another OC. With regard to contraceptive efficacy, the life-table analysis showed a value of 0.032% for method failure and 0.114% for patient failure. The correspondent Pearl-Index is 0.062 and 0.22. The new drug was found acceptable by more than 90% of the women involved in the trial. Dysmenorrhea present in the "switchers" mostly disappeared on the new OC, while body weight and blood pressure remained virtually unchanged. Thus, it can be concluded that blood pressure and body weight behaviour is similar to that seen with other low-dose OCs. The new combined pill offers excellent cycle stability and has a very favourable effect on dysmenorrhea. The number of clinically diagnosed thrombotic events documented in this study was 0.65 per 1000 woman-years (TWY) and does not exceed the range of events seen in groups of women using non-hormonal methods of contraception (Oxford-FPA study 0.4/TWY and RCGP study 0.8/TWY).

PIP: Efficacy, cycle control, tolerance, and adverse events were studied in a clinical phase IV study using a new progestogen, gestodene, in an amount of 75 mcg combined with 30 mcg ethinyl estradiol. The study was performed as a multicenter trial in 96,000 patients over a period of 6 cycles. 1/2 of the patients taking the new preparation were 1st-time OC users, the other 1.2 switched from another OC. With regard to contraceptive efficacy, the life table analysis showed a value of 0.032% for method failure and 0.114% for patient failure. The correspondent Pearl Index is 0.062 and 0.22. The new drug was found acceptable by more than 90% of the women involved in this trial. Dysmenorrhea present in those who switched disappeared for the most part with this new OC, while body weight and blood pressure remained virtually unchanged. Thus, it can be concluded that blood pressure and body weight behavior is similar to that seen with other low-dose OCs. The new combined pill offers excellent cycle stability and has a very favorable effect on dysmenorrhea. The number of clinically diagnoses thrombotic events documented in this study was 0.65/1000 woman-years (TWY) and does not exceed the range of events seen in groups of women using nonhormonal methods of contraception (Oxford-FPA study 0.4/TWY and RCGP study 0.8/TWY).

Is sonographic flow imaging useful in the differential diagnosis of adrenal masses?

This prospective study was carried out to assess the ability of colour Doppler ultrasound (CDUS) and power flow imaging to differentiate between benign and malignant adrenal masses. We examined 56 adrenal masses, discovered at CT, in 47 patients who had undergone CT for known extraadrenal malignancy or unrelated benign conditions. The nature of the masses was confirmed by histopathology or assessed for likelihood of malignancy by CT appearance, MRI appearance, recent development or increase in size. In none of the adrenal masses was blood flow detected by colour Doppler or power imaging, despite optimizing scanning parameters for the detection of slow flow. We conclude that colour Doppler ultrasound and power imaging do not help in differentiating benign from malignant adrenal masses.

Safety aspects of a coumarin-troxerutin combination regarding liver function in a double-blind placebo-controlled study.

OBJECTIVE: Coumarin is reported to elevate liver function tests (LFT) values. In a prospective, placebo-controlled, clinical trial, efficacy and safety of a coumarin-containing combination (SB-LOT) were evaluated in the treatment of chronic venous insufficiency. Here, we report on the drug safety of coumarin with special respect to liver reaction. METHODS: 114 patients were treated with SB-LOT (30 mg coumarin and 180 mg troxerutin t.i.d.) and 117 with placebo during a period of 16 weeks. LFT values (ALT, AST, AP and gamma-GT) were monitored at baseline, 4, 6, 8, 12 and 16 weeks of therapy. Adverse drug reactions were assessed regarding causality. Additionally, lymphocyte proliferation test was used to identify allergic reactions. Logistic regression analysis was performed to identify possible risk factors. RESULTS: No serious adverse drug reactions occurred. Elevations of LFT were assessed as biochemical abnormality. Specific clinical symptoms such as jaundice did not occur. Only 1 patient reported fatigue and exhaustion. Logistic regression estimated a basic risk for elevation of LFT of 4.9% under SB-LOT and 2.1% under placebo. Hepatitis in the history and diseases of the liver were identified as risk factors. CONCLUSION: This evaluation contributes to safety data of SB-LOT in man. LFT elevation is transient and the low risk of the SB-LOT therapy to increase LFT value can be limited when risk factors are considered.

[Activation of blood coagulation and fibrinolysis after angiocardiography with ionic and non-ionic contrast media]. / Aktivierung von Blutgerinnung und Fibrinolyse nach Angiokardiographie mit ionischem und nichtionischem Kontrastmittel.

PURPOSE: To study the effects of a ionic (amidotrizoate) and a non-ionic x-ray contrast medium (iopromid) during routine levocardiography and coronary angiography, we employed assays that detect reaction products of thrombin and plasmin to assess the activation of the haemostatic system. METHODS: Subsequent to informed consent, 20 patients were randomly assigned to receive either amidotrizoate or iopromid during standard levocardiography and coronary angiography in a double-blind comparative study. Groups were comparable in respect of age, weight, sex and severity of the disease. No anticoagulation was provided. Coronary angiography was performed according to a standardised protocol. Consumption of contrast media and duration of the examination were comparable in both groups. RESULTS: Thrombin generation (F.1+2) and thrombin activity (TAT) were higher with the ionic contrast medium but did not attain statistical significance. Fibrin generation and degradation as expressed by D-dimer fibrin split products was significantly increased in patients who had been receiving amidotrizoate (p < 0.05, U-Test). CONCLUSION: The non-ionic x-ray contrast medium induced significantly less haemostatic activation in vivo than did the ionic medium amidotrizoate. These data suggest that earlier in vitro observations of more pronounced anticoagulant effects of ionic x-ray contrast media are of limited significance for the evaluation of in vivo effects of x-ray contrast media on haemostatic function.

Statistical procedures in clinical pharmacology: decision-theorectic foundations.

The function of statistical analysis is to reach optimal decisions in situations of principal uncertainty. The foundations of statistical procedures are experiments X, whose distributions PX are characterised by random samples. Within given classes of distributions (distribution hypothesis) mathematical statistics make optimal procedures available, which allow conclusions on the real properties of PX. The use of optimal procedures minimises the risk of incorrect decisions made on the basis of random samples (principle of greatest chance). Statistics, however, refrain from any statement on the quality of the decision to which a procedure in a certain situation leads. Against a decision-theoretic background of statistical decisions the growing complexity of clinical-pharmacological test models leads to the necessity of using descriptive-statistical methods on an even larger scale. The aim should be to reduce the number of individual parameters to a few important factors, so that the relation between the number of trial subjects on the one hand and the number of parameters on the other remains valid for meaningful statistical statements.

The efficacy and safety of a coumarin-/troxerutin-combination (SB-LOT) in patients with chronic venous insufficiency: a double blind placebo-controlled randomised study.

BACKGROUND: The objective was to evaluate the oedema-protective effect of a vasoactive drug (coumarin/troxerutin [SB-LOT]) plus compression stockings in patients suffering from chronic venous insufficiency after decongestion of the legs as recommended by the new guidelines. PATIENTS AND METHODS: 231 patients were randomly assigned medical compression stockings plus SB-LOT (90 mg coumarin and 540 mg troxerutin per day) or medical compression stockings plus placebo for the first 4 weeks and SB-LOT or placebo for the second 12 weeks of the study. The primary efficacy endpoint was the lower leg volume measured by well-established water plethysmometry. RESULTS: 226 patients were evaluated. After ceasing compression stockings, an edema protective effect was detected in the SB-LOT-group but not in the controls. Recurrence of leg volume increase was by 6.5 +/- 12.1 ml and by 36.7 +/- 12.1 ml in the SB-LOT and placebo group, respectively (p = 0.0402). The local complaint score and general aspects of quality of life were also superior for the SB-LOT-group (p = 0.0041). Significant differences were also observed with regard to clinical global impression and therapeutic effect. No serious adverse drug reaction or clinically relevant impairment of laboratory parameters occur. CONCLUSION: This study confirms the oedema-protective effect of SB-LOT in chronic venous insufficiency and provides a treatment option for patients who discontinue compression after a short time.

Nonneurologic indications for MRI. Technological advances have broadened applications.

Traditionally used for neurologic indications, magnetic resonance imaging (MRI) is now being used to diagnose the most common musculoskeletal, vascular, hepatic, biliary, adrenal, and renal disorders. Drs Schnitker and Light discuss the nonneurologic indications for MRI as both a primary and an adjunct study. The advantages and disadvantages of fast scanning and open MRI are also presented.