Fluticasone propionate/formoterol for COPD management: a randomized controlled trial.

PURPOSE: To evaluate fluticasone propionate/formoterol (FP/FORM) in COPD. PATIENTS AND METHODS: COPD patients with forced expiratory volume in 1 s (FEV1) ≤50% predicted and ≥1 moderate/severe COPD exacerbation in the last 12 months were randomized to FP/FORM 500/20 or 250/10 µg bid, or formoterol (FORM) 12 µg bid for 52 weeks. The primary outcome was the annualized rate of moderate/severe COPD exacerbations. RESULTS: In total, 1,765 patients were randomized. There were fewer discontinuations with FP/FORM 500/20 µg (20.6%) and 250/10 µg (24.0%) compared with FORM (26.1%). None of the two FP/FORM doses reduced the moderate/severe exacerbation rate versus FORM (rate ratios [RR]: 0.93; P≤0.402). There was a trend toward a lower moderate/severe exacerbation rate with FP/FORM 500/20 µg versus FORM in patients with ≥2 exacerbations in the preceding year (RR: 0.79; P=0.084). Pre- and post-dose FEV1 and forced vital capacity were greater with FP/FORM 500/20 µg versus FORM (P≤0.039). There was a trend toward a lower EXAcerbations of Chronic pulmonary disease Tool (EXACT) exacerbation rate with FP/FORM 500/20 µg versus FORM (RR: 0.87; P=0.077). There were more St George's Respiratory Questionnaire for COPD (SGRQ-C) responders with FP/FORM 500/20 µg than FORM (odds ratios [OR] at weeks 6, 23 and 52 ≥1.28; P≤0.054). EXACT-respiratory symptoms total and breathlessness scores were lower with both FP/FORM 500/20 µg and 250/10 µg versus FORM (P≤0.066). Acute ß2-agonist-induced effects and 24-hour Holter findings were similar for all treatments. Mean 24-hour urinary cortisol was similarly reduced with both FP/FORM doses. Radiologically confirmed pneumonia was seen in 2.4%, 3.2% and 1.5% of FP/FORM 500/20 µg, FP/FORM 250/10 µg and FORM-treated patients, respectively. Adverse events were otherwise similar across treatment groups. CONCLUSION: FP/FORM did not reduce exacerbation rates versus FORM. Numerical benefits were observed with FP/FORM 500/20 µg versus FORM for secondary variables, including lung function, EXACT exacerbations, SGRQ-C and EXACT-respiratory symptoms total and breathlessness scores. Few efficacy differences were evident between FP/FORM 250/10 µg and FORM. Pneumonia was more frequent in FP/FORM-treated patients, although the absolute difference was low. Adverse events were otherwise similar between treatments.

Molecular composition of recycled organic wastes, as determined by solid-state 13C NMR and elemental analyses.

Using solid state (13)C NMR data and elemental composition in a molecular mixing model, we estimated the molecular components of the organic matter in 16 recycled organic (RO) wastes representative of the major materials generated in the Sydney basin area. Close correspondence was found between the measured NMR signal intensities and those predicted by the model for all RO wastes except for poultry manure char. Molecular nature of the organic matter differed widely between the RO wastes. As a proportion of organic C, carbohydrate C ranged from 0.07 to 0.63, protein C from <0.01 to 0.66, lignin C from <0.01 to 0.31, aliphatic C from 0.09 to 0.73, carbonyl C from 0.02 to 0.23, and char C from 0 to 0.45. This method is considered preferable to techniques involving imprecise extraction methods for RO wastes. Molecular composition data has great potential as a predictor of RO waste soil carbon and nutrient outcomes.

Rare sellar region tumors.

We present three cases of rare intracranial midline tumor in the sellar region, often mimicking pituitary adenomas clinically. We describe their symptoms, radiological and pathomorphological features. The first case is a pituitary adenoma producing growth hormone with ganglion cell differentiation. In addition, a rare intracranial granular cell tumor of sellar region and germinoma of pituitary fossa are also presented. All tumors were resected and histologically analyzed. Their biological behaviour was favorable with a 10-year follow-up demonstrating no recurrent tumor mass.

Hypnotic susceptibility and alterations in subjective experiences.

Pavlov has described hypnosis as a partial sleep. A contemporary approach to this altered state of consciousness will be discussed. Under laboratory conditions subjective and behavioral data will be analyzed after hypnotic induction, shamanic trance and relaxation with listening to music. Role of different cortical regions will be shown after different hypnotic inductions as a function of hypnotic susceptibility. The importance of context will be underlined as an important factor in the possible alteration of consciousness.

[Traumatic dissection of the aorta (external and iatrogenic traumas)]. / A traumás aortadissectio (külsó és iatrogén traumák).

The authors are looking over the notion of traumatic aortic dissection and introducing to its forms accepted today. The definition of the disease changed within the advance of medicine, it has been on the one hand tightened and increased on the other. In the era of the non-invasive medicine, with the external mechanical injuries also the physical and mental strains has been regarded as causes of the aortic dissection. By the widening spread of the invasive medicine a new category of aortic dissection has been appeared namely the iatrogenic trauma. Nowadays, those aortic dissections may be regarded as traumatic ones, which have been connected with external mechanical (indirect) or internal iatrogenic (direct) injuries. According to recent data, the incidence of traumatic aortic dissection is growing. The reasons for this are the expanding motorization, arteriosclerosis and the increasing age of life.

Epidemiology and clinicopathology of aortic dissection.

STUDY OBJECTIVES: To determine the incidence and mortality as well as to analyze the clinical and pathologic changes of aortic dissection. DESIGN AND SETTING: A population-based longitudinal study over 27 years on a study population of 106,500, including 66 hospitalized and 18 nonhospitalized consecutively observed patients. MEASURES: Analysis of data from the medical, surgical, and autopsy records of patients with aortic dissection. RESULTS: Altogether, 86 cases of aortic dissection were found in 84 patients, corresponding to a 2.9/100,000/yr incidence. Sixty-six of the 84 patients (79%) were admitted to the hospital, and 18 patients (21%) died before admission. Their ages ranged from 36 to 97 years, with a mean of 65. 7 years. The male/female ratio was 1.55 to 1. A total of 22.7% of the hospitalized patients died within the first 6 h, 33.3% within 12 h, 50% within 24 h, and 68.2% within the first 2 days after admission. Six patients were operated on, with a perioperative mortality of two of six patients and a 5-year survival of two of six patients. All patients who were not operated on died. Pain was the most frequent initial symptom. Every patient had some kind of cardiovascular and respiratory sign. Neurologic symptoms occurred in 28 of 66 patients (42%). Five patients presented with clinical pictures of acute abdomen and two with acute renal failure. Trunk arteries were affected in 33 of the 80 autopsied cases (41%), and rupture of aorta was seen in 69 cases (86%). In five cases, spontaneous healing of dissection was also found. The ratio of proximal/distal dissections was 5.1 to 1. All 18 prehospital cases were acute. Fifty-nine cases (89.4%) were acute at admission, and 7 cases (10.6%) were chronic dissections. Hypertension and advanced age were the major predisposing factors. CONCLUSION: Aortic dissection was the initial clinical impression in only 13 of the 84 patients (15%). Thus, 85% of the patients did not receive immediate appropriate medical treatment. For this reason, these late-recognized and/or unrecognized cases may be regarded as an untreated or symptomatically treated group, whose course may resemble the natural course of aortic dissection.

[Abdominal catastrophes and limb arterial occlusions caused by acute aortic dissection. Experiences of a longitudinal population-based study of 28 years]. / Akut aortadisszekcióhoz társuló hasi katasztrófák és végtagartéria elzáródások. Definiált populáción folytatott 28 éves longitudinális vizsgálat tapasztalatai.

The authors pursue longitudinal studies since 1972 on a defined population of 106,000 relating to several questions of the aortic dissection. Till now, in 90 patients 93 cases of the aortic dissection were found. In seven patients, the aortic dissection was complicated with the clinical and pathological symptoms of surgical diseases. The vascular complications of the aortic dissection caused obstruction of coecomesenteric arteries with severe ischemic signs in four patients, obstruction of iliac arteries in two patients and the left sublavian artery in one another. In an additional patient with a chronic recurrent pancreatitis, the acute aortic dissection as an acute exacerbation of chronic pancreatitis was considered. It makes known in a short report of cases the clinicopathological features of vascular complications of the thoracoabdominal aortic dissections. Their pathomechanisms as well as the possibilities of their diagnosis and treatment are reviewing in detail.

[Differential diagnostic value of clinical symptoms of aortic dissection]. / Az aortadissectio klinikai tüneteinek differenciáldiagnosztikai jelentösége.

Acute aortic dissection is a relatively common catastrophic illness, in which the circulation of any major artery arising from the aorta may be compromised and any organ or organ system may become ischemic. Hereby a protean clinical picture may be developed. This disease is characterized by migration of symptoms which may be difficult to evaluate. It is expedient to range the various symptoms produced by aortic dissection among cardiac, pulmonary, cerebral and neurologic, abdominal and renal groups. This may be especially helpful diagnostically if more than one system has been involved. An accurate differential diagnosis can be made if the history and presented signs are carefully evaluated.

Correlation of EEG asymmetry and hypnotic susceptibility.

Hypnosis research of the last decades confirmed that some cortical regions show characteristic modification of spontaneous brain electrical activity as a function of hypnotic responsiveness. Using FFT spectrum of 16 channel EEG recording, it was demonstrated that in highly susceptible subjects the right parieto-temporal region show more electric power than the left one while the low susceptibles have left side predominance or equilibrated power in all derivations. If a specific (Ericksonian) indirect hypnosis induction was administered, the same right side preponderance could be recorded in low susceptibles, too. On the basis of these results we can confirm the importance of the right parieto-temporal associative area in the alteration of consciousness characterizing hypnotic state.

[Clinicopathology of aortic dissection]. / Az aortadissectio klinikopatológiája.

A population based study was carried out over a 25-year period (1972-1997) to disclose the clinical and pathological features of aortic dissection based on the analysis of 79 (71 acute and 8 chronic) consecutive cases of disease observed in an defined population of 106,000 inhabitants. Of the 79 patients 65 (82.3%) were admitted to hospital and 14 (17.7%) died out of hospital. Their ages ranged from 36 to 97 years (mean, 65.4 yrs), 49 (62.0%) were men and 30 (38.0%) were women with means 61.2 and 69.1 years, respectively. The male/female ration was 1.6:1. All but two operated patients died. The pain was the leading symptom. Every patients had some kind of cardiovascular and respiratory signs. Neurologic symptoms occurred in 27/65 (41.5%) patients. In five patients the clinical picture of abdominal catastrophe and in two patients renal failure occurred. The major vessels were affected in 32/75 (42.7%) autopsies. Aortic rupture were seen in 64/79 (81.0%) cases. Five spontaneous healings were observed. The hypertension, the advantaged age and the arteriosclerosis are regarded as the mean predisposing factors.

[Incidence and mortality of aortic dissection]. / Az aortadissectio incidenciája és mortalitása.

A population-based study was carried out over a 24-year period between January 1, 1973 and December 31, 1996 to determine the incidence and mortality of the aortic dissection in an administratively defined population of 106,000 inhabitants. The study comprises the consecutive cases of both inpatients and outpatients. Altogether, 74 cases of aortic dissection were found corresponding to 2.89%/year incidence. From the 74 patients 60 were admitted to hospital and 14 outpatients dead before the admission. In the first half of the observational interval (1973-84) 32 cases and in it's second half (1985-96) 42 cases were occurred with incidence of 2.50%/year and 3.28%/year, respectively. The higher incidence of the cases in the second half interval was explained by the significant increase of the autopsy rate of the dead outpatients. The male/female ratio was 1:1.6. The age ranged from 36 years to 97 years with a mean of 66.4 years and the women have had higher mean by the 7.0 years (p < 0.05). The mortality was explosively abrupt at the onset of the disease. Fourteen outpatients (18.9% of the total) died suddenly before admission and in the inpatients after the admission 28.4% died within the first hour, 44.6% within 12 hours, 62.2% within 24 hours and 75.5% within the first two days. Six patients were surgically treated and their perioperative mortality was 2/6, one month survived 4/6 and three years survived 3/6. The other 71 patients died. On the bases of the above-mentioned facts this work may be considered as an representative study. Hereby, the incidence of the aortic dissection in Hungary at least 3.0/100,000/year or rather 300 cases/year should be assessed.

[Aortic dissection]. / Az aortadissectio.

The aortic dissection is an expanding intramural hematoma in the aortic wall separating its layers. That is the most common catastrophic condition of the aorta. Its incidence in Hungary about 3.0%/000/year may be appreciated. The mortality rate of the untreated cases exceeds the 90 per cent. The dissection begins by an intimal tear or by a medial hemorrhage, seldom. The progressing hematoma results in a false lumen running parallel with the true aortic lumen. On the basis of the location of the primary intimal tear the dissection may be proximal or distal. The inherited or acquired medial weakness and the hypertension are the main etiologic factors. Some pathological findings refer to predisposing role of the atherosclerosis. The ischemia caused by the dissection may damage any organ. The clinical picture is characterized by the polymorphism and the migration of the clinical signs. The suspicion of the disease may be raised on the basis of the anamnesis and the clinical picture. The diagnosis may be confirmed by the rutin chest roentgenograms and by the angiography, CT, MRI and ultrasonic examinations. The transoesophageal echocardiography is the best diagnostic tool. The treatment is medical and/or surgical. Advances in the surgical treatment brought turn in the very poor prognosis.

[A case of herpes simplex encephalitis requiring surgical management]. / Herpes simplex encephalitis mütéti kezelést igénylö esete.

The authors report about surgical treatment of herpes simplex encephalitis, although conservative management of this disease is the method of choice in the first place. They draw a lesson from this case that certain cases of large space occupying lesions of infectious origin leading to brain stem compression may require surgical management, even if they customary treatment is conservative.

Cell kinetic analysis in recurrent neuro-epithelial tumours.

The biological behaviour of brain tumours is variable. In the majority of cases, recurrence of the tumour is the decisive factor determining the prognosis and individual survival of patients suffering from a neuro-epithelial neoplasm. The time course of recurrences varies significantly according to differences in tumour cell proliferation. In this study, predictive factors concerning the expected prognosis following the resection of neuro-epithelial tumours were investigated with the aim of improving the histological diagnosis. A retrospective analysis of 22 recurrent neuro-epithelial tumours (recurrent tumour group) and 12 neuro-epithelial tumours with a minimum survival rate of 5 years following radical excision (cured tumour group) was performed by means of flow cytometry and immunohistochemistry using the MIB 1 antibody. Histological samples of the subgroups of the recurrent tumour group, i. e., the primary tumours and their recurrences were compared with each other, and the subgroups were compared with the cured tumour group. A multivariate analysis of the data was performed with the BMPD Hotteling T square test. A statistically significant difference was found between the recurrent tumour group (primary tumours + recurrences) and the cured group from every investigated aspect. On the other hand, no difference could be found between the sub-groups primary tumours and their recurrences. All tumours in the recurrent group had an accelerated, active cell cycle, which was expressed in a high proliferation activity. The following conclusion was drawn: an increased risk of recurrence is to be expected in neuro-epithelial tumours characterized by: an S-phase fraction higher than 6-9%, an MIB 1-labelled cell number higher than 2-3/high-power fields, and a number of mitoses higher than 1/10 high-power fields.

[Experience with urinary conduit procedures]. / Az álhólyag (vizelet conduit) képzés módszereivel szerzett megfigyeléseink.

Between 1989 and 1993, 32 urinary conduit procedures were carried out at the Department of Gynaecological Oncology, National Institute of Oncology Budapest. Of these, 26 patients with pelvic tumour underwent total or anterior pelvic exenteration. The urinary conduit operation was performed in associated with radical hysterectomy due 2 vesico-urinary fistula in 2 patients, and as a palliative procedure in 4 instances (bladder fistula 2, bladder fistula and ureter occlusion 1 and bilateral ureteric obstruction 1). Mean age of the patients was 46, range 20-73 years. 23 patients underwent bladder replacement with "Bricker pouch" or ileal conduit, mostly in the first 2 years, and as a palliative procedure. Kock pouch was constructed in 3 and an Indiana pouch in 6 women. There was no intraoperative mortality. 3 patients died in the postoperative period, none of them due to complication of the urinary diversion procedure. Postoperative bleeding occurred in one ileal conduit that ceased spontaneously and in one Indiana pouch that required reoperation. Haematuria was a common finding in the first 3 to 5 days following surgery. Urinary leakage in the abdominal cavity lasting for 7 to 10 days postoperatively occurred in almost all instances in those who underwent a Bricker pouch. This did not require surgical intervention. 3 patients with Bricker pouch experienced pyelonephritis. Continent pouches are emptied by self-catheterization, 6-8 times daily. There were no other early complications. Techniques of urinary diversion are discussed.

Perioperative complications of 116 radical hysterectomies and pelvic node dissections.

Perioperative morbidity and mortality were studied in 116 patients who underwent radical hysterectomy and lymph node dissection. Type II radical hysterectomy was performed in two, type III in 97, type IV in 12 and type V in five patients, and the perioperative morbidity was assessed accordingly. Because of the short follow-up time the late sequelae could not be evaluated. There was no operative death. Haemorrhage was the most common complication and it was more frequent and serious in type IV and V classes. Prolonged bladder atony was also frequent, particularly in type IV radical hysterectomy. The infection rate was comparable. One patient developed ureteric fistula, and one woman had ureteric stricture. Lymphocyst formation, nerve damage, lymphoedema and thromboembolic disease were rarely encountered and there was no bowel obstruction. Injury to the great vessels was a major problem. It appears that the rate of complications in this study is acceptable and comparable with or favourable to other reported series. In spite of this, every effort should be made to reduce the operative morbidity as far as possible.

Ewing's sarcoma in the occipital bone. Case report.

The head is a very rare primary site for Ewing's sarcoma which occurs most often in the long bones of the extremities and in the pelvis. This report describes an unusual case of Ewing's sarcoma arising from the occipital bone in a seven year old girl. The tumour compressed the venous sinuses, thus lowering the intracranial pressure resulted in temporary recovery which made the diagnosis difficult.

Effect of metoprolol and pindolol monotherapy on plasma lipid- and lipoprotein-cholesterol levels (including the HDL subclasses) in mild hypertensive males and females.

Forty-five patients with mild hypertension were treated for 2 months with either metoprolol or pindolol in a randomized, blind, crossover study. The effects of metoprolol (100-300 mg/day) and pindolol (5-15 mg/day) on triglyceride (TG), cholesterol (C), high-density lipoprotein cholesterol (HDL-C), and HDL subfraction (HDL2-C and HDL3-C) levels were compared in males and females separately. Pindolol and metoprolol significantly elevated (10% above baseline level) the plasma TG level in both males and females. After metoprolol treatment, the HDL-C level remained unchanged in both sexes; however, a shift was found between HDL2-C and HDL3-C:HDL2-C decreased and a concomitant elevation in HDL3-C was observed. Pindolol significantly decreased total C, HDL-C, and HDL2-C levels in males. A similar trend (although the changes were not significant) was found in females. The results demonstrate the role of beta blockers in the inhibition of TG-rich lipoprotein elimination. These findings suggest that during long-term administration of metoprolol and pindolol, risks and benefits from beta-blocker therapy must be carefully considered. Continuous monitoring of lipid profiles is suggested during this treatment in order to avoid the potential worsening effect of beta blockers on risk factors of ischemic heart disease.

Persistent hypoglycemia due to hyperinsulinemia, hypoglucagonemia and mild adrenal insufficiency.

The case history of a patient with serious hypoglycemia (with 0.6-3 mmol/l blood glucose) persisting for eight years and treated as epilepsy during the time of observation is reported. As the cause of hypoglycemia hyperinsulinemia, hypoglucagonemia, and moderate adrenal insufficiency was suggested. The pattern of secretion of insulin as well as of C-peptide indicated, that hyperinsulinemia was induced by hypersecretion of immunoreactive insulin. As the cause of hypersecretion of insulin insulinoma might have been ruled out. Hypoglucagonemia was shown by the low concentration of plasma glucagon. Adrenal insufficiency seemed to be due to ACTH deficiency. Replacement therapy with dexamethasone or administration of ACTH led to elevation of the blood glucose to normal, and the plasma cortisol also reached normal levels. On the basis of other data as well as of our own investigations we suggest a central origin of the illness. The patient has been free from his complaints with normal blood glucose and plasma cortisol concentrations for two years.