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Purpose: The effects of metformin on prostate volume and prostate-specific antigen (PSA) were investigated.

Amaç: Soğuk, mesane fonksiyonunda değişik şekillerde hasara neden olabilen stres indükleyici bir faktördür. Bu çalışmada kortikosteroid ve antihistaminik tedavisinin akut ve kronik olarak indüklenmiş soğuk stres üzerine etkilerini araştırmak amaçlanmıştır.Gereç ve Yöntemler: 42 adet dişi sıçanrastgele yedi gruba ayrılmıştır. Gruplar şu şekildedir;Kontrol grubu, Akut soğuk stress (ACS) grubu; ACS+ kortikosteroid (CORT) grubu; ACS+CORT+antihistaminik grubu; Kronik soğuk stress (CCS) grubu; CSS CORT grubu; CSS+CORT+antihistaminik grubu. Bu uygulamalardan sonraki 15. günde, genel anestezi altında sıçanlara sistektomi uygulandı ve mesaneleri çıkarıldı. Çıkarılan dokular %10 nötral tamponlu formalin içerisinde fikse edilip takip edildikten sonra hematoksilen eozin ve Toluidin mavisi ile boyandı.Bulgular: Mast hücre sayısına göre yapılan değerlendirmede, kontrol grubuna kıyasla en yüksek değer CCS grubunda gözlenmiştir. En düşük değer CCS + CORT grubunda elde edilmiştir. CCS grupları arasındaki karşılaştırmaya göre, lamina propriadaki en yüksek polimorfonükleer lökosit (PNL) değerleri CCS grubunda görülürken, CORT ve CORT+Antihistaminik tedavilerinin, lamina propriadaki PNL değerlerini önemli ölçüde azalttığı gözlendi. Epiteldeki PNL sayıları ACS ve CCS gruplarında yüksek iken, CORT ve/veya antihistaminik ile tedavi edilen ACS ve CCS gruplarındaki sonuçların kontrol grubundakilerle benzer olduğu ortaya çıkmıştır. CORT’a ek olarak antihistaminik enjeksiyonun, CCS'deki epitelde bulunan lenfosit sayısını, sadece CORT'dan daha verimli bir şekilde azalttığı görüldü.Sonuç: Mevcut çalışma, kortikosteroid tedavisinin, enflamatuar hücre infiltrasyonunu ve mast hücre sayısını azalttığını ortaya koymuştur. Özellikle kronik soğuk stresde daha belirgin bir iyileşme olduğu gözlenmektedir., Objective: Cold is a stress-inducing factor that can cause changes in bladder function in various ways. The present study is intended to investigate the effects of corticosteroid and antihistaminic treatment on acutely and chronically induced cold stress.Material and Methods: Forty-two female rats were randomly divided into seven groups as follows: Control group; Acute cold-stress (ACS) group; ACS+ corticosteroid (CORT) group; ACS+CORT + Antihistaminic group; Cronic cold-stres (CCS) group; CSS+CORT group; CSS+CORT+Antihistaminic group. On the 15th day after these treatments, bladders of the rats were harvested for histopathological examinations under general anesthesia and fixed with 10% neutral buffered formaline. Hematoxylin and eosin and toluidine blue stainings were performed.Results: The comparison based on mast cell count yielded the highest value in the CCS group in comparison to the control group. The lowest value was harvested in the CCS + CORT group. The comparison between the CCS groups revealed the highest polymorphonuclear leucocyte (PNL) values in the lamina propria in the CCS group, whereas the CORT and CORT + Antihistaminic treatments were found to have significantly decreased the PNL values in the lamina propria. While the PNL counts in the epithelium were high in the ACS and CCS groups, the results in the ACS and CCS groups that were treated with CORT and/or antihistaminic were revealed to be similar with those in the control group. It was discovered that antihistaminic injection in addition to CORT decreased the lymphocyte counts in epithelium in CCS more efficiently than CORT alone did.Conclusion: The present research revealed that corticosteroid treatment reduced inflammatory cell infiltration and decreased mast cell count. A more evident amelioration was observed particularly in chronic cold stress.

Introduction We examined the effect of seasonal variation on sexual behavior and its relationship with testosterone levels. The existence of the inhibiting effect of cold stress on sexual behavior and testosterone levels was our hypothesis. Material and methods A total of 80 cases, aged between 20 and 35 years old, were enrolled. Blood samples for testosterone, FSH, LH, and prolactin were obtained twice from each participant at the same time of day (before 10 am). The first samples were taken in January and February, the months which have the average lowest heat days (-15.9°C and -14.6°C, respectively) in our region. The second samples were taken in July and August, which has the average highest heat days (25.4°C and 26.1°C, respectively) in our region. Two times IIEFs (International Index of Erectil Function) were fulfilled at the same day of taking blood samples. The frequency of sexual thoughts and ejaculation were questioned by asking “How many times did you imagine having sex?’’ and “How many times did you ejaculate in a week?”. The body mass index of the participants in the study was calculated in the winter and in the summer. Results There were significant differences in terms of IIEF scores, frequency of sexual thoughts and ejaculations, BMI (Body mass index), and both testosterone and FSH levels between the winter and summer measurements. We did not find any significant differences with regards to prolactin and LH levels. Conclusions Although testosterone levels are within normal limits in both seasons, its level in cold months is less than in hot months. Testosterone levels can change according to the season. The impact of cold seasons in particular should be taken into account when evaluating testosterone levels and sexual status, as well as the other influences (social, cultural).

Introduction In this animal study, we reviewed the histomorphological findings in rabbit kidneys after a high number of high-energy shock wave applications and observed if there were any cumulative effects after repeated sessions. Material and methods We formed 2 groups, each consisting of 8 rabbits. Group 1 received 1 session and group 2 received 3 sessions of ESWL with a 7 day interval between sessions, consisting of 3500 beats to the left kidney and 5500 beats to the right kidney per session. The specimens of kidneys were examined histomorphologically after bilateral nephrectomy was performed. For statistical analysis, 4 groups of specimens were formed. The first and second groups received 1 session, 3500 and 5500 beats, respectively. The third and fourth groups received 3 sessions, at 3500 and 5500 beats per each session, respectively. The sections were evaluated under a light microscope to determine subcapsular thickening; subcapsular, intratubular and parenchymal hemorrhage; subcapsular, intersitital, perivascular and proximal ureteral fibrosis; paranchymal necrosis; tubular epithelial vacuolization; tubular atrophy; glomerular destruction and calcification. Results In histopathological examinations capsular thickening, subcapsular hematoma, tubuloepithelial vacuolisation, glomerular destruction, parenchymal hemorrhage, interstitial fibrosis, and perivascular fibrosis were observed in all groups. In statistical analysis, on the basis of perivascular fibrosis and tubular atrophy, there was a beats per session dependent increase of both. Conclusions The detrimental effects from ESWL are dose dependent but not cumulative for up to 3 sessions. Histopathological experimental animal studies will aid in understanding local and maybe, by means of these local effects, systemic effects.

To compare the outcomes of flexible ureterorenoscopy (F-URS) with extracorporeal shock wave lithotripsy (ESWL) for the treatment of upper or mid calyx kidney stones of 10 to 20 mm. A total of 174 patients with radioopaque solitary upper or mid calyx stones who underwent ESWL or F-URS with holmium:YAG laser were enrolled in this study. Each group treated with ESWL and F-URS for upper or mid calyx kidney stones were retrospectively compared in terms of retreatment and stone free rates, and complications. 87% (n = 94) of patients who underwent ESWL therapy was stone free at the end of 3rd month. This rate was 92% (n = 61) for patients of F-URS group (p = 0.270 p 0.05). Retreatment was required in 12.9% of patients (n = 14) who underwent ESWL and these patients were referred to F-URS procedure after 3rd month radiologic investigations. The retreatment rate of cases who were operated with F-URS was 7.5% (n = 5) (p = 0.270 p 0.05). Ureteral perforation (Clavien grade 3B) was occured in 3 patients (4.5%) who underwent F-URS. Fever (Clavien grade 1) was noted in 7 and 5 patients from ESWL and F-URS group, respectively (6.4% vs 7.5%) (p = 0.78 p 0.05). F-URS and ESWL have similar outcomes for the treatment of upper or mid calyx renal stones of 10-20 mm. ESWL has the superiority of minimal invasiveness and avoiding of general anethesia. F-URS should be kept as the second teratment alternative for patients with upper or mid caliceal stones of 10-20 mm and reserved for cases with failure in ESWL.

Isolated brain stem tuberculoma: a case report and review of the literature Approximately 5 to 10% of tuberculosis cases involve brain and central nervous system. Tuberculosis involving central nervous system (CNS) due to haematogenous spread is not a rare entity. CNS manifestations may be meningitis, solitary tuberculomas, abscess, infarct or milier parenchymal disease. In this case report, we discuss a 17-year- old female with isolated pontin tuberculoma and comorbidity of genital tuberculosis and review the literature.

Distal üreter tașlarının tedavisinde; üreterorenoskopik litotripsi (ÜRS) ve vücut dıșı șok dalga litotripsinin (ESWL) etkinliklerini karșılaștırması landı.YÖNTEMTek distal üreter tașı olan hastaların dosyaları geriye dönük incelendi. Hastalar uygulanan tedavi seçeneklerine göre ESWL ve ÜRS gruplarına ayrıldı. Gruplar; tedavi bașarısı ve komplikasyon oranları açısından karșılaștırıldı.BULGULARESWL ve ÜRS gruplarında sırasıyla 112 ve 108 hasta yer aldı. Yaș, taș boyutu ve cinsiyet değișkenleri gruplar arasında farklılık göstermedi. Ortalama taș boyutu 10,8 mm’di. Operasyon sonrası tașsız hasta oranı, ÜRS grubunda %89,8 ve ESWL grubunda%59,8’di. Gruplar arası fark istatistiksel olarak anlamlıydı (p, AIMTo compare the effi ciency of ureterorenoscopic lithotripsy (URS) and extracorporeal shock wave lithotripsy (ESWL) in the treatment of distal ureteral stones.METHODSThe data of all patients with a single distal ureter stone were investigated, retrospectively. The patients were divided into two groups according to the management options as ESWL and URS. The success and complication rates of the groups were compared.RESULTSThere were 112 and 108 patients in ESWL and URS groups, respectively. Patients’ age, stone size and gender were similar in both groups. The average stone size was 10.8 mm. Postoperative success rate defined as the removal of all the stones was higher in URS group (89.8%) than ESWL group (59.8%), and the difference was significant (p

1980’lerin sonundan itibaren, prostata özgü antijenin (prostate specific antigen, PSA) klinikte kullanılmaya bașlanmasıyla prostat kanseri hastalarının kaderi dramatik olarak değiști. Günümüzde daha fazla sayıda erkek lokalize, küçük, daha az agresif ve ölümcülolmayan prostat kanseri tanısı almaktadır. Klinik olarak lokalize prostat kanserinin tedavisinde, günümüzde radikal prostatektominin yanı sıra, prostatın kriyo–cerrahi ile ablasyonu, brakiterapi ve yüksek yoğunluk odaklı ultrasonografi de alternatif tedavi seçenekleri olarak kabul edilmektedir.Bu derlemede, birincil sonuç olarak lokalize prostat kanserinde fokal tedavi alternatiflerinin bașarısı ve komplikasyon oranları belirlemeyi ladık. Derlemenin ikincil sonucu ise bu ișlemler için uygun olan aday hastaların tanımlanmasıydı.“Prostat kanserinin fokal tedavi alternatifleri”, “yüksek yoğunluk odaklı ultrasonografi ve prostat kanserinin kriyocerrahisi” ve “prostat kanserinin radyofrekans ablasyonu” tanımlamalarıyla Medline taraması yaptık. Toplamda 1173 makale değerlendirildi ve bunlardan içerik olarak uygun bulunan 45 tanesi derlemede kullanıldı.Konuyla ilgili kontrollü çalıșma yoktu. Amerikan Üroloji Derneği kılavuzları, prostatın kriyocerrahi ablasyonunu tedavi edici bir yöntem olarak kabul etmektedir; ancak cerrahi ve cerrahi dıșı alternatiflerle kıyaslandığında, daha az morbidite ve olasılıkla aynı tedavietkinliğine sahip minimal invasiv bir yöntem olarak geliștirilmesine rağmen yüksek yoğunluk odaklı ultrasonografi ise hala deneysel olarak kabul edilmektedir.Girișim yapılmadan düzenli takip edilme kriterlerini yakalayan ancak aktif tedavi șansını kaçırma hissiyle anksiyete yașayan hastalarda, fokal tedaviler iyi alternatifler olabilir. Ancak, fokal tedavi seçeneği düșük ve orta dereceli riski olan hastalar için saklanmalıdır.Radyolojik ve klinik evre sırasıyla T2b ve T2a’nın altında olmalıdır. Ek olarak, adaylar alternatiflerin deneysel olduğu ve zaman içinde tedavi seçeneğinin değiștirilmesine ihtiyaçları olabileceği yönünde bilgilendirilmelidirler. Yakın gelecekte fokal tedavi alternatifleri daha gerçekçi tedavi seçeneklerine dönüșebilirler, ancak kanıta dayalı veri sağlamak için iyi desenlenmiș, çok merkezli randomize prospektif çalıșmalara ihtiyaç vardır., The destiny of prostate cancer patients has been dramatically changed since the introduction of prostate specifi c antigen (PSA) into clinical use in late 1980s. Currently more men are diagnosed with localized, small, less aggressive and non-lethal prostatic carcinoma. Besides radical prostatectomy, cryosurgical ablation of the prostate, brachytherapy and high-intensity focused ultrasound have been accepted as alternative treatment options in clinically localized prostatic carcinoma.In this review, we aimed to evaluate the success and complication rates of alternative focal treatment options as the primary outcome. The secondary outcome of this review was to define the candidate patients eligible for these procedures.We searched the Medline using specifi ed expressions including “focal treatment alternatives of prostatic carcinoma”, “high-intensity focused ultrasound and cryosurgery of prostatic carcinoma” and “radiofrequency ablation of prostatic carcinoma”. A total of1173 papers related to the focal treatment options were analyzed and only 45 of them related to the subject were included.There wasn’t a controlled trial dealing with the topic. American Urologic Association guidelines have accepted cryosurgical ablation of the prostate as a therapeutic option; however the high-intensity focused ultrasound is still considered as an experimental treatment option, although it has been developed as a minimally invasive procedure with reduced morbidity and potentially with the same therapeutic efficacy in comparison with the surgical or non surgical options.For patients meeting the variable criteria for regular follow up visits without intervention but experiencing anxiety with the feeling of losing active treatment options, focal therapies may be ideal alternatives. However, focal therapy options should be spared for patientswith low to moderate risks. The radiologic and clinical stages should be below T2b and T2a, respectively. In addition, all candidates should be informed that the alternatives are considered as experimental and they may need an alternative treatment option in time.Focal therapy alternatives may be more realistic treatment options in the near future; however, well designed multicenter prospective randomized trials are required to provide evidence based data.

Üreter taşları acilde sık rastlanan bir durumdur. Tedavide obstrüksiyonu acil gidermek için double-J kateter konabilir. Double-J kateter takılırken ya da üreterorenoskopik litotripsi yapılırken taş ya da parçaları retrograd böbreğe migrasyon olabilir. Ancak spontan retrograd migrasyon nadir bir durumdur. Bu makalede üreter taşına bağlı obstrüktüf üropati ve enfeksiyon gelişen hastaya acil double-J kater koyma işleminden sonra taşın spontan böbreğe retrograd migrasyonundan bahsettik. Benign prostat hiperplazisinin bu olasılığı artırabileceği sonucuna vardık., Renal colic due to ureteral stones is a common medical situation in the emergency. Double j ureteral stent insertion may lead relief of obstruction. Stones or fragments may migrate to the kidney via retrograde way during insertion of double j stent or ureterorenoscopic lithotripsy. Besides this, spontaneous retrograde migration is an unusual phenomenon. In this article, we reported a case with spontaneous retrograde migration of a ureteral stone which was secondary to the insertion of double j stent for relief of obstructive uropathy and infection. We revealed that benign prostatic hyperplasia (BPH) might increase this probability.

AMAÇ: Hastane şartlarında uzman doktorların yaptığı sünnetlerin komplikasyon oranlarının saptanmasıdır.YÖNTEMLER: 2004-2012 yılları arasında Kars Devlet Hastanesi, Kafkas Üniversitesi Tıp Fakültesi Hastanesi, Kars Özel Bioanaliz Polikliniği ve Kars Özel Şifa Polikliniğinde 0-19 yaşları arasındaki 2220 hastaya Üroloji ve Genel Cerrahi Uzmanları tarafından dorsal-ventral slit ve eksizyon tekniği uygulanarak sünnet yapıldı. Sünnet sonrası oluşan komplikasyonlar retrospektif olarak değerlendirilmiştir.BULGULAR: Çalışmamızda komplikasyon oranı %3.3 olup, kanama %1.65 oranı ile ilk sırayı alırken, sırasıyla enfeksiyon %1.2, yetersiz sünnet % 0.25, anesteziye bağlı komplikasyonlar %0.20 olara saptanmıştır. Ayrıca bir hastada inklizyon kisti oluşmuştur.SONUÇ: Sünnet cerrahi bir işlem olup, hastane şartlarında ve işin uzmanı hekimler tarafından yapıldığında ciddi komplikasyonlar büyük oranda azalmaktadır., OBJECTIVE: Our aim is to evaluate the complication rates of circumcisions performed by specialists in the hospitals.METHODS: 2220 patients with the ages ranging between 0 and 19 years old were circumcised by urologists and general surgeons in Kars State Hospital, Kafkas University Faculty of Medicine, Kars Private Bioanaliz and Şifa outpatient clinics between June 2004 and September 2012. Dorsal ventral slit and excision technique was preferred for all patients. The procedures were performed in hospitals with obeying the surgical sterilization rules.RESULTS: The overall complication rate was 3.3%; bleeding was the most common one with a rate of 1.65%, infection in 1.2%, inadequate excision in 0.25% and complications related with anesthesia in 0.2%. Bleeding complications were not serious and only 11 cases (0.49%) required re-intervention under local anesthesia, of these, hemorhagic diatesis was found in 4. İnfection that threatened the life of the patient was not observed.CONCLUSION: Circumcision is a surgical modality. It had rules to be obeyed like the other surgical modalities and a technique. Serious complications are very rare, if deferred to these rules and performed by specialists in the hospitals’ conditions. We advise to investigate the patients for hemorhagic diatesis prior to circumcision. Key words: circumcision, complications

Aşırı aktif mesane (AAM) hayat kalitesi üzerine belirgin etkisi olan yaygın bir tıbbi durumdur. Tedavi yaklaşımı davranışsal ve farmakolojiktir. İlk farmakolojik tedavi alternatifi tolerabilitesi, etkinliği ve uzun dönem komplians gibi sınırlayıcı faktörleri olan antikolinerjik ajanlardır. AAM’ nin patofizyolojisinin anlaşılması ve farmakolojik tedavideki alternatif ajan arayışı, bu durumun tedavisi için yeni moleküllerin geliştirilmesini sağlamıştır. Bu moleküllerin antikolinerjik ilaçlarla benzer etkileri olup, yan etkilerinden kaçınmaktadırlar., Overactive bladder (OAB) is a prevalent condition that has a significant impact on quality of life. The usual treatment approach is both behavioral and pharmacological. The first-line pharmacological treatment commonly utilizes anticholinergic agents, which may be limited by their tolerability, efficacy, and long-term compliance. Developments in elucidating the pathophysiology of OAB and alternative targets for pharmacological therapy have led to newer agents being developed to manage this condition. These agents which have alternate mechanism of action and avoid the anticholinergic side effects.

Bireyler yaşam tarzlarını modifiye ve kontrol ederek, fertilite potansiyellerini bir dereceye kadar arttırabilir veya muhafaza edebilirler. Yaşam tarzlarının modifikasyonu, üreme sağlığı ve fertilite potansiyelini arttıracak veya bozacak çeşitli faktörlere maruziyeti belirleyebilir. Bu makalede, yaşam tarzı seçimlerine göre değişebilecek modifiye edilebilir bazı faktörleri ve onların üreme sağlığına olan etkilerini güncel tıbbi literatür eşliğinde sunuyoruz., Individuals have roles in preserving or increasing their fertility potential to a degree by controlling and modifying their life styles. Life styles modification may determine exposure to various factors that may improve or disprove reproductive health and fertility potential. Herein, we try to present some modifiable factors varies according to the life style preferences and their effects on reproductive health in the light of current medical literature.

AMAÇ: İnfertil erkeklerde varikoselin cerrahi olarak düzeltilmesinden sonraki geç dönemde spermiogram değerlerine ve fertiliteye katkısını belirlemek için hastalar retrospektif olarak araştırıldı.YÖNTEMLER: Çalışmamızda Ocak 2004-Haziran 2012 yılları arasında Kars Devlet Hastanesi ve Kars Kafkas Üniversitesi Tıp Fakültesi'nde infertilite nedeniyle ameliyat yöntemine bakılmaksızın varikoselektomi yapılan ve kayıtlarına ulaşılan 240 hasta retrospektif olarak tarandı. Spermiogram ve doppler USG incelemesi olan ve tıbbi kayıtlarına ulaşılan 148 hasta çalışmaya dahil edildi. 46 hastanın medikal kayıtlarına ulaşılamadı, onlar da telefonla aranarak fertilizasyon durumları soruldu ve yeni bir semen analizi yaptırmak üzere kliniğimize davet edildi. Varikoselektomi yapılıp eşi gebe kalan ancak düşükle sonlanan çiftler fertil olarak kabul edildi.BULGULAR: Hastaların ameliyat yaşları 19-38 arasında olup, yaş ortalamaları 29.3 olarak hesaplandı. Preoperatif semen analizinde, hastaların %70.6' sında (n: 131) oligospermi, %22.4' ünde (n: 43) oligoastenospermi ve %7' sinde (n: 14) oligoastenoteratozoospermi mevcuttu. Hastaların 125’ inin (%64.7) postoperatif spermiogram tetkiklerinde, WHO kriterlerine göre sperm konsantrasyonu, motilitesi veya morfolojisinin en az birinde artış saptandı. 80 çiftte (%41.1) varikoselektomi sonrasında ek bir tedavi ve yardımcı üreme tekniği kullanılmadan gebelik gerçekleştiği öğrenildi.SONUÇ: Biz çalışmamızda, infertil hastaların sperm parametrelerinde ve spontan gebelik oranında artış saptadık. Varikoseli olan infertil hastalara varikoselektomiyi tavsiye etmekteyiz., OBJECTIVE: In our study, we retrospectively analysed the effect of surgical varicocele repair on sperm analysis and fertility status of infertile patients in the late period.METHODS: We retrospectively searched the records of 240 patients who underwent surgical varicocele repair between January 2004 and June 2012 in Kars State Hospital and Kafkas University Faculty of Medicine. 148 patients with obtained full medical records, sperm analysis and doppler ultrasonography were included in the study. We could not reach the postoperative data of 46 patients and they were asked current status of fertility on the phone and invited to our department for new semen analysis. Couples whose pregnancies resulted with abortions after varicocele repair were accepted as fertile.RESULTS: The mean age of the patients was 29.3 years ranging between 19 and 38 years old. Preoperative sperm analysis showed oligospermia, oligoasthenospermia and oligoasthenoteratozoospermia in 70.6%, 22.4% and 7% of cases, respectively. Postoperative semen anlaysis revealed improvements in at least one of sperm concentration, motility and morphology in 125 patients according to the WHO criteria and 80 of couples had spontaneous fertilization after varicocelectomy without any requirement of assisted reproductive techniques.CONCLUSION: Our study showed increase in parameters of semen analyses and spontaneous pregnancies in patients after varicocelectomy. We advise varicocelectomy to the infertile cases with varicoceles.

Aşırı aktif mesane (AAM) hayat kalitesi üzerine belirgin etkisi olan yaygın bir tıbbi durumdur. Tedavi yaklaşımı davranışsal ve farmakolojiktir. İlk farmakolojik tedavi alternatifi tolerabilitesi, etkinliği ve uzun dönem komplians gibi sınırlayıcı faktörleri olan antikolinerjik ajanlardır. AAM' nin patofizyolojisinin anlaşılması ve farmakolojik tedavideki alternatif ajan arayışı, bu durumun tedavisi için yeni moleküllerin geliştirilmesini sağlamıştır. Bu moleküllerin antikolinerjik ilaçlarla benzer etkileri olup, yan etkilerinden kaçınmaktadırlar., Overactive bladder (OAB) is a prevalent condition that has a significant impact on quality of life. The usual treatment approach is both behavioral and pharmacological. The first-line pharmacological treatment commonly utilizes anticholinergic agents, which may be limited by their tolerability, efficacy, and long-term compliance. Developments in elucidating the pathophysiology of OAB and alternative targets for pharmacological therapy have led to newer agents being developed to manage this condition. These agents which have alternate mechanism of action and avoid the anticholinergic side effects.