The economics of medical therapy for lower urinary tract symptoms associated with benign prostatic hyperplasia

Medical therapy is currently the most popular treatment choice for lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Because medical therapy of BPH-related LUTS is considered a life-long strategy, short- and long-term cost considerations should play a major role in therapeutic decision-making. The effectiveness in terms of long and short amelioration of symptoms, flow rate, and quality of life are well documented for 5α-blockers and 5α-reductase inhibitors as well as for the gold standard treatment for BPH, transurethral resection of the prostate and minimally invasive therapies. Short-and long-term safety concerns also are well documented for these various treatment options. On the contrary, short- and long-term costs have been less well studied and comparisons depend on the model or analyses undertaken in the few studies available. However, the economic studies based on prospective clinical trial data that have become available throughout the past several decades allow us to rationalize our use of α-blockers, 5α -reductase inhibitors, and combination therapy, taking into consideration age, severity of symptoms, prostate volume, prostate-specific antigen, and the differential response of the various medications (and combination) in selected patients. Based on current studies, 5α -blockers generally provide cost-effective therapy for most patients, whereas 5α-reductase therapy and combination therapy provide cost-effective treatment for patients with larger prostate glands or higher baseline prostate-specific antigen levels.     

Hippocampal pathology in refractory temporal lobe epilepsy: T2-weighted signal change reflects dentate gliosis.

BACKGROUND: The MR and pathologic features of hippocampal sclerosis (HS) are well described and include volume decrease and T2-weighted signal increase for MRI, and neuron cell loss and gliosis for pathology. OBJECTIVE: To confirm the established correlation between hippocampal volumes and neuron cell counts, and to study the still controversial association between signal change and gliosis. METHODS: The authors studied 44 patients (22 men and 22 women; mean age at surgery, 37 years) with refractory temporal lobe epilepsy. Quantitative assessment of hippocampal volumes and T2 relaxometry, and neuron and glial cell count in the region CA1 and molecular layer of the dentate gyrus was performed. The proportion of glial fibrillary acidic protein (GFAP)-positive glial cells (reactive astrocytes) was indicated. RESULTS: In a stepwise regression, the ipsilateral hippocampal volume was predicted best by the neuron cell count in the dentate gyrus (p = 0.005, r = 0.4). Hippocampal T2 time, however, was predicted best by the glial cell count in the dentate gyrus (p = 0.01, r = 0.4). None of the other cell counts contributed to either model. In the dentate, 31% of the glial cells were reactive astrocytes, whereas in CA1, 5% were reactive. CONCLUSION: The results confirmed the correlation between hippocampal volumes and neuron cell counts. T2-weighted signal increase in the hippocampus was mainly influenced by gliosis in the dentate gyrus, where a high proportion of glial cells show abnormal activity. This activity may reflect changes important in the development of hippocampal epileptogenicity.     

Tooth movement and cytokines in gingival crevicular fluid and whole blood in growing and adult subjects.

INTRODUCTION: Tooth movement has been studied largely with respect to the force required for tipping when pressure distribution varies along the length of the periodontal ligament. But important factors for effective canine translation include the nature and magnitude of applied stress and the patient's cell biology. The purpose of this research was to test 3 hypotheses: (1) the velocity of tooth translation (v(t)) is related to applied stress and growth status, (2) a threshold of stress accounts for the lag phase, and (3) v(t) is correlated with the ratio (AI) of 2 cytokines (IL-1beta, IL-1RA) measured in gingival crevicular fluid (GCF) and stimulated whole blood (SWB). METHODS: Continuous maxillary canine retraction stresses of 13 kPa and 4, 26, or 52 kPa were applied bilaterally in 6 growing and 4 adult subjects for 84 days. Dental models and GCF samples were collected at 1- to 14-day intervals. Cytokines were measured in GCF and SWB cell cultures. RESULTS: V(t) was positively related to stress and was higher in growing subjects (P = .001). It was also related to AI(GCF) in growers (R2= 0.56) and nongrowers (R2= 0.72). Canines moved with 52 kPa showed a lag phase, and postlag phase AI(GCF) was twice that of lag phase AI(GCF). Mean v(t) and associated AI(GCF) during the postlag phase were nearly double the values for canines moved with 13 and 26 kPa. SWB production of cytokines was dose-dependent. For growing subjects, SWB IL-1RA was correlated with v(t) (R = 0.70-0.72), and AI(SWB) and IL-1beta concentrations were correlated with AI(GCF) (R = 0.73-0.78). CONCLUSIONS: V(t) varied with growth status and stresses < or = 52 kPa; stresses of < 52 kPa showed no lag phase; and equivalent stresses yielded subject-dependent differences in v(t), which correlated with cytokines in GCF and SWB.     

Epidemiological study on the hepatotoxicity of occupational toluene exposure

Summary In a cross-sectional study of 181 male workers of a rotogravure printing plant, most of whom were exposed to toluene levels well above the GDR threshold limit values, 55 subjects revealed pathological liver screening values (activities of serum aspartate aminotransferase, alanine amino-transferase, gamma glutamyltransferase; liver size). The differential diagnostic examination showed in 51 out of these 55 subjects an association with competing factors such as alcohol abuse (78%) and overweight (40%), to a slight extent disorders of fat and carbohydrate metabolism and of the gallbladder. Drug intake did not play any role. The variance and regression analyses of the biochemical data have shown that alcohol significantly and considerably increases the activities of all three enzymes tested. Bodyweight had a similar, but less pronounced, significant effect. On the other hand, in subjects with a higher alcohol intake the activities of liver enzymes in highly toluene exposed subgroups were significantly and clearly lower than among slightly toluene exposed workers.     

Comparison of the efficacy and safety of ciclesonide 160 μg once daily vs. budesonide 400 μg once daily in children with asthma

Ciclesonide is an onsite-activated inhaled corticosteroid (ICS) for the treatment of asthma. This study compared the efficacy, safety and effect on quality of life (QOL) of ciclesonide 160 microg (ex-actuator; nominal dose 200 microg) vs. budesonide 400 microg (nominal dose) in children with asthma. Six hundred and twenty-one children (aged 6-11 yr) with asthma were randomized to receive ciclesonide 160 microg (ex-actuator) once daily (via hydrofluoroalkane metered-dose inhaler and AeroChamber Plus spacer) or budesonide 400 microg once daily (via Turbohaler) both given in the evening for 12 wk. The primary efficacy end-point was change in forced expiratory volume in 1 s (FEV1). Additional measurements included change in daily peak expiratory flow (PEF), change in asthma symptom score sum, change in use of rescue medication, paediatric and caregiver asthma QOL questionnaire [PAQLQ(S) and PACQLQ, respectively] scores, change in body height assessed by stadiometry, change in 24-h urinary cortisol adjusted for creatinine and adverse events. Both ciclesonide and budesonide increased FEV1, morning PEF and PAQLQ(S) and PACQLQ scores, and improved asthma symptom score sums and the need for rescue medication after 12 wk vs. baseline. The non-inferiority of ciclesonide vs. budesonide was demonstrated for the change in FEV1 (95% confidence interval: -75, 10 ml, p = 0.0009, one-sided non-inferiority, per-protocol). In addition, ciclesonide and budesonide showed similar efficacy in improving asthma symptoms, morning PEF, use of rescue medication and QOL. Ciclesonide was superior to budesonide with regard to increases in body height (p = 0.003, two-sided). The effect on the hypothalamic-pituitary-adrenal axis was significantly different in favor of ciclesonide treatment (p < 0.001, one-sided). Both ciclesonide and budesonide were well tolerated. Ciclesonide 160 microg once daily and budesonide 400 microg once daily were effective in children with asthma. In addition, in children treated with ciclesonide there was significantly less reduction in body height and suppression of 24-h urinary cortisol excretion compared with children treated with budesonide after 12 wk.     

Effect of dialysis flux and membrane material on dyslipidaemia and inflammation in haemodialysis patients.

BACKGROUND: Dyslipidaemia, inflammation and oxidative stress are prominent risk factors that potentially cause vascular disease in haemodialysis patients. Dialysis modalities affect uraemic dyslipidaemia, possibly by modifying oxidative stress, but the effects of dialyser flux and membrane material on atherogenic remnant particles and oxidized low-density lipoproteins (LDL) are unknown. METHODS: We performed a randomized crossover study in 36 patients on haemodialysis to analyse the effect of dialyser flux and membrane material on plasma lipids, apolipoproteins and markers of inflammation and oxidative stress. Stable patients on low-flux dialysis with polysulphone for >/=6 weeks were assigned to high-flux polysulphone or high-flux modified cellulose with similar dialyser surface area and permeability characteristics and crossed over twice every 6 weeks. RESULTS: Thirty patients completed the study per protocol. Treatments with high-flux polysulphone and modified cellulose lowered serum triglyceride (by 20% and 10%, respectively; P<0.05) and remnant-like particle cholesterol by 32% (P<0.001) and 11% (NS) after the first 6 weeks of treatment. Oxidized LDL decreased significantly with high-flux polysulphone, but not with modified cellulose. Apolipoproteins CII and CIII were reduced, whereas the ratio CII/CIII was increased (all P<0.05). Acute-phase proteins and LDL and high-density lipoprotein cholesterol remained unaffected. CONCLUSIONS: This randomized crossover study demonstrates a potent effect of high-flux haemodialysis on uraemic dyslipidaemia. Polysulphone membrane material showed superiority on oxidatively modified LDL, an indicator of oxidative stress in haemodialysis patients.     

Rat model of experimental bacterial prostatitis

A reproducible rat model of chronic bacterial prostatitis was developed employing a defined bacterial pathogen to study the pathophysiology of acute and chronic bacterial prostatitis. The progression of inflammation and its consequences following the retrograde introduction of bacteria through the acute and finally the chronic stages of prostatitis can be documented with microbiological, histological, ultrastructural and immunologic data. This model has many striking similarities to the natural history of human chronic bacterial prostatitis and further microbiological, antimicrobial and immune modulation or manipulation of this model should help us to further delineate the pathogenic mechanisms involved in this chronic infective disease.Zum Studium der Pathophysiologie der akuten und chronischen bakteriellen Prostatitis wurde ein reproduzierbares Rattenmodell für die chronische bakterielle Prostatitis entwickelt, dabei wird ein definierter bakterieller Erreger verwendet. Das Fortschreiten der Entzündung und ihrer Folgeerscheinungen nach retrogradem Einführen der Bakterien über die akuten und schließlich die chronischen Stadien der Prostatitis kann mit mikrobiologischen, histologischen, ultrastrukturellen und immunologischen Daten dokumentiert werden. Dieses Modell hat bemerkenswerte Ähnlichkeiten mit dem natürlichen Verlauf der chronischen bakteriellen Prostatitis beim Menschen; weitere mikrobiologische, antimikrobielle und immunmodulierende oder anderweitige Veränderungen dieses Modells dürften dazu beitragen, daß die Pathomechanismen dieser chronischen Infektionskrankheit weiter abgeklärt werden können.