The medical therapy of prostatic symptoms study: what will we learn?

Until recently, benign prostatic hyperplasia (BPH) was thought of as a relatively uncomplicated disease process resulting from age-related enlargement of the prostate gland, which was thought to cause all of the symptoms associated with the disease. Prostatectomy was considered the state-of-the art treatment of BPH. Advances in our understanding of the pathogenesis of BPH and the relationship among clinical signs and symptoms has allowed for the development of pharmacologic therapies for this disorder, namely, selective alpha-blockers and 5-alpha-reductase inhibitors. These 2 classes of drugs have been demonstrated to be safe and effective for the treatment of BPH. Evidence supports different mechanisms of action, suggesting that, when used in combination, these therapies may act synergistically. The Medical Therapy of Prostatic Symptoms study was designed, in part, to test this hypothesis. Initial results of the trial are presented in this article.     

The diversification of Heliconius butterflies: what have we learned in 150 years?

Research into Heliconius butterflies has made a significant contribution to evolutionary biology. Here, we review our understanding of the diversification of these butterflies, covering recent advances and a vast foundation of earlier work. Whereas no single group of organisms can be sufficient for understanding life's diversity, after years of intensive study, research into Heliconius has addressed a wide variety of evolutionary questions. We first discuss evidence for widespread gene flow between Heliconius species and what this reveals about the nature of species. We then address the evolution and diversity of warning patterns, both as the target of selection and with respect to their underlying genetic basis. The identification of major genes involved in mimetic shifts, and homology at these loci between distantly related taxa, has revealed a surprising predictability in the genetic basis of evolution. In the final sections, we consider the evolution of warning patterns, and Heliconius diversity more generally, within a broader context of ecological and sexual selection. We consider how different traits and modes of selection can interact and influence the evolution of reproductive isolation.     

A reappraisal of the central effects of botulinum neurotoxin type A: by what mechanism?

Botulinum neurotoxin A (BoNT/A) is a metalloprotease that enters peripheral motor nerve terminals and blocks the release of acetylcholine via the specific cleavage of the synaptosomal-associated protein of 25-kDa. Localized injections of BoNT/A are widely employed in clinical neurology to treat several human diseases characterized by muscle hyperactivity. It is generally assumed that the effects of BoNT/A remain localized to the injection site. However, several neurophysiological studies have provided evidence for central effects of BoNT/A, raising the issue of how these actions arise. Here we review these data and discuss the possibility that retrograde axonal transport of catalytically active BoNT/A may explain at least some of its effects at the level of central circuits.     

Research: Is resection of tumours involving the pelvic ring justified? : A review of 49 consecutive cases

INTRODUCTION: Pelvic surgery is challenging and impacts significantly on limb and visceral function, thus, raising the question "is heroic surgery justifiable". This study assessed the functional, oncologic and surgical outcomes following pelvis tumour resections. METHODS: Between 1996-2003, 49 patients (mean age 43 years) underwent pelvic tumour resections- 38 primary malignant tumours, 5 secondary tumours and 6 benign tumours. Bone tumours comprised 5 osteosarcomas, 5 Ewings sarcomas, and 12 chondrosarcomas. Of the soft tumours, 9 were of neural origin. Tumours involved the ilium, acetabulum, pubic bones, sacrum or a combination of these. Functional assessment was performed and no patient had metastases at presentation. RESULTS: There were 41 limb sparing resections and 8 hindquarter amputations. Surgical margins were intralesional (1), marginal (13), wide (26), and radical (3). Of limb sparing surgery, prosthetic reconstructions were performed in 10 patients, biologic reconstructions in 6, a combination of these in 3 and no reconstruction in others. There was 1 intraoperative death, 7 local recurrences and 19 metastases. Death from disease occurred at a mean of 14.2 months with a mean followup of 27 (1-96) months. Amputation and periacetabular resections had worse functional outcomes. Emotional acceptance was surprisingly high. CONCLUSION: Pelvic resections are complex. Functional outcome is significantly affected by surgery. Disease control is similar to limb tumours. Emotional acceptance of surgery in survivors was surprisingly high. Major pelvic resection for malignancy appears justified.     

Do prognoses of patients with second primary cancers differ from those of patients with no prior cancer? A population-based study

BackgroundSome cancer survivors develop second primary cancers. However, differences in prognosis between patients who have and have not had prior cancer have not been established. We examined and compared the prognoses of such patients.MethodsUsing the record-linked database of the population-based Cancer Registry of Osaka Prefecture and Vital Statistics in Japan, we identified patients aged ≥ 40 years who were diagnosed with stomach (n = 70,946), colorectal (n = 60,582), or lung (n = 58,016) cancers during 1995–2009. We defined these cancers as index cancers. Patients were classified into three groups according to history of prior cancer and interval between diagnosis of index and prior cancer: single (no prior cancer or interval of ≥10 years), synchronous (interval ≤3 months), and metachronous (interval 3 months to 10 years). The 5-year prognosis from index cancer diagnosis was investigated using the Kaplan–Meier method and log-rank test.Results5-year prognoses of patients with synchronous stomach and colorectal cancers were significantly worse than that of patients with single primary, about 60 % of these patients’ deaths being attributable to the prior cancer. In contrast, 5-year prognoses of patients with metachronous primaries were not significantly worse, except for men with colorectal cancer. The percentages of index cancer deaths were 1.7–4.3 times those for non-index cancer deaths.ConclusionA prior cancer contributed to an inferior prognosis in patients with synchronous stomach and colorectal cancers. The prognoses of patients with metachronous primaries were more affected by the index than by the prior cancer, whereas most of them had similar or better prognoses than did patients with a single primary. This finding would help to relieve cancer survivors’ anxiety about their development and prognosis of metachronous second primary cancer.     

Justinian II and Carmagnola: a Byzantine rhinoplasty?

The Carmagnola statue, although undoubtedly a Byzantine Emperor, still holds its secret as to who it actually represents, and how his nose got that way. Our tentative conclusions concerning the possibility of Justinian's Indian nasal reconstruction only raise other questions. If Justinian Rhinometos did have a nasal reconstruction, how was the knowledge of the technique transmitted from northern India to the Byzantine Empire by the end of the 7th century? And if Justinian did have his "rhinokopia" surgically corrected, would this represent the first case of nasal reconstruction in the western world, 900 years before the triumphs of Tagliacozzi?     

The effect of consecutive transmeridian flights on alertness,sleep–wake cycles and sleepiness: A case study

ABSTRACT

Travel across time zones disrupts circadian rhythms causing increased daytime sleepiness, impaired alertness and sleep disturbance. However, the effect of repeated consecutive transmeridian travel on sleep–wake cycles and circadian dynamics is unknown. The aim of this study was to investigate changes in alertness, sleep–wake schedule and sleepiness and predict circadian and sleep dynamics of an individual undergoing demanding transmeridian travel. A 47-year-old healthy male flew 16 international flights over 12 consecutive days. He maintained a sleep–wake schedule based on Sydney, Australia time (GMT + 10?h). The participant completed a sleep diary and wore an Actiwatch before, during and after the flights. Subjective alertness, fatigue and sleepiness were rated 4 hourly (08:00–00:00), if awake during the flights. A validated physiologically based mathematical model of arousal dynamics was used to further explore the dynamics and compare sleep time predictions with observational data and to estimate circadian phase changes. The participant completed 191?h and 159 736?km of flying and traversed a total of 144 time-zones. Total sleep time during the flights decreased (357.5?min actigraphy; 292.4?min diary) compared to baseline (430.8?min actigraphy; 472.1?min diary), predominately due to restricted sleep opportunities. The daily range of alertness, sleepiness and fatigue increased compared to baseline, with heightened fatigue towards the end of the flight schedule. The arousal dynamics model predicted sleep/wake states during and post travel with 88% and 95% agreement with sleep diary data. The circadian phase predicted a delay of only 34?min over the 16 transmeridian flights. Despite repeated changes in transmeridian travel direction and flight duration, the participant was able to maintain a stable sleep schedule aligned with the Sydney night. Modelling revealed only minor circadian misalignment during the flying period. This was likely due to the transitory time spent in the overseas airports that did not allow for resynchronisation to the new time zone. The robustness of the arousal model in the real-world was demonstrated for the first time using unique transmeridian travel.     

Translational proteomics: what can you do for true patients?

Matching the right medical strategy to the right patient is the key for modern clinical oncology. To this aim, we have many delicate drugs designed to target in elegant ways critical proteins identified in cancer cells. However, clinical oncologists and multidisciplinary groups devoted to treating patients in an integrative fashion have histology and an TNM staging system as the most relevant biomarkers to decide therapeutic approaches for our patients. In addition, the most used drugs are classical chemotherapeutic compounds such as cisplatin, epirrubicin, irinotecan, oxaliplatin, and so on. Thus, new targeted therapies, surgery, radiotherapy, and chemotherapy will live together causing a duality for the immediate future. We will try to delineate unmet needs for clinical oncologists that would add value for cancer proteomics in terms of true patients.     

Globin gene switching: A paradigm or what?

The delineation of the beta-globin locus control region has led to a new understanding of the developmental regulation of the beta-globin gene cluster. It now seems that globin gene switching is effected through the sequential and mutually exclusive interaction of the locus control region with the embryonic, fetal and adult stage specific globin genes.     

Which contacts of patients with meningococcal disease carry the pathogenic strain of Neisseria meningitidis? A population based study

Objectives: To determine the prevalence of the pathogenic strain of Neisseria meningitidis in contacts of patients with meningococcal disease, and to determine which contact groups are likely to be carriers and warrant chemoprophylaxis. Design: Population based study. Setting: Norwegian county of Telemark. Subjects: 1535 primary contacts of 48 patients with meningococcal disease, and 78 secondary contacts. Interventions: Carriers of the pathogenic strain were treated with rifampicin. All household members and kissing contacts under 15 years of age were treated with oral penicillin. Contacts were taught to recognise the symptoms of meningococcal disease. Results: In 27 of 48 cases investigated, contacts carrying the pathogenic strain of N meningitidis were found. A total of 42 such contacts were identified. Contacts were stratified into three classes according to the assumed closeness of contact with patients. In class 1 (household members and kissing contacts) the prevalence of the pathogenic strain was 12.4% (95% confidence interval 5.5% to 19.3%). In classes 2 and 3 the prevalence was 1.9% (0.9% to 3.4%) and 1.6% (0.14% to 3.1%). Conclusions: There is a high rate of carriage of the pathogenic strain of N meningitidis in patients’ household members and kissing contacts, and this supports the practice of giving chemoprophylaxis to these contacts. The prevalence of carriage among other contacts is 2-3 times that found in the general population (0.7%); the benefits of chemoprophylaxis to these contacts may be marginal.

Key messages

• Contacts of patients with meningococcal disease have a 12.4% (95% confidence interval 5.5% to 19.3%) risk of carrying the pathogenic meningococcus if they are kissing contacts or household members
• The risk of carriage of the pathogenic strain for two groups of contacts less close than household members or kissing contacts is 1.9% (0.9% to 3.4%) and 1.6% (0.14% to 3.1%)

     

Applying GPS to the study of primate ecology: A useful tool?

Data on the spatiotemporal distribution of resources can be collected and plotted using GPS (global positioning system) and GIS (geographical information system) technologies. By combining such data with information on foraging and ranging behavior of nonhuman primates, one can analyze the influence of resource distribution on social organization and group cohesion. We investigated the abilities of a three-channel GPS receiver to collect location data under varying canopy densities in both temperate and tropical forests. Eighty randomly selected points were sampled in a beech–maple forest in northeast Ohio, USA; 65 points also were sampled at several tropical forests in Costa Rica and Trinidad. At each point we attempted to obtain a GPS position fix; we also determined the speed of satellite acquisition and measured canopy density using a spherical densiometer. The ability to obtain a reading differed greatly between the two forest types (χ² = 53.79, P < 0.001). Ninety-seven percent of all attempts were successful in the temperate forest, whereas only a 34% acquisition rate was obtained in the tropical forests. Logistic regression showed that the probability of obtaining a reading in Neotropical forests was 75% but only when canopy cover was less than 20%. Thus, these minimal-channel GPS units may be of limited utility for behavioral ecologists working in closed-canopy Neotropical forests. Am. J. Primatol. 46:167–172, 1998. © 1998 Wiley-Liss, Inc.     

Do treatment protocols improve end results? A study of survival of patients with multiple myeloma in Finland.

OBJECTIVE--To determine whether patients with multiple myeloma treated in three consecutive clinical trials of chemotherapy of the Finnish Leukaemia Group during 1979-85 had a more favourable prognosis than both patients treated in the trial area before the trials and those treated in the rest of Finland. DESIGN--Comparison of the time trend in survival of patients living in the trial area with that of patients living in the rest of Finland. SETTING--Trial area covered 17 of the 21 main hospital districts in Finland (serving more than two thirds of patients with multiple myeloma). PATIENTS--663 Men and 690 women in the trial area and 318 men and 307 women in the reference area aged under 71 in whom multiple myeloma was diagnosed during 1959-85. In the trial area the disease was diagnosed in 455 men and 493 women in 1959-78 and in 208 men and 197 women in 1979-85; in the reference area it was diagnosed in 234 men and 227 women in 1959-78 and in 84 men and 80 women in 1979-85. MAIN OUTCOME MEASURES--Five year cumulative relative survival rates during 1959-85, annual relative survival rates in the first seven years of follow up during 1979-85, and fitted annual relative survival rates in the first five years of follow up during 1959-85. RESULTS--During the first two years of follow up the annual relative survival rates did not differ between the two areas, but in the next five years of follow up patients in the trial area did better than those in the reference area. For cases diagnosed in 1979-85 the difference in the five year cumulative relative survival rates between patients in the trial area and those in the reference area was 10%, those in the trial area doing better. Generalised proportional hazards regression analysis of the first five years of follow up showed that the patients in the trial area had a survival advantage over those in the reference area. The model with the best fit included year of follow up, time of diagnosis, the joint effect of year of follow up and time of diagnosis, and the joint effect of area and time of diagnosis. CONCLUSION--The patients in the trial area benefited from the clinical trials, which suggests that the use of a treatment protocol improves the end results of treatment. In other words, the results favour a systematic treatment schedule in preference to a schedule determined by the free choice of a clinician.