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  Citation statistics : Table of Contents
   2013| May-August  | Volume 6 | Issue 2  
    Online since April 23, 2018

 
 
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ORIGINAL RESEARCH ARTICLES
A study in pleiotropy – Jalili syndrome
Pratibha Nair, Tasneem Obeid, Ghazi Omar Tadmouri, Najib Al-Khaja, Ismail K Jalili
May-August 2013, 6(2):233-240
DOI:10.7707/hmj.v6i2.248  
Jalili syndrome, first described 25 years ago in a Palestinian family, is a rare autosomal recessive genetic disorder that is characterized by the comorbid appearance of cone–rod dystrophy (CRD) and amelogenesis imperfecta. To date, 71 patients with this condition belonging to 17 different families have been reported worldwide. Studies into the molecular aetiology of Jalili syndrome have identified mutations in the CNNM4 gene, located on chromosome 2q11. Other members of this protein family have been shown to be involved in mineral transport. We postulate a role for the CNNM4 protein in metal ion transport and homeostasis and especially in the transport of magnesium ions. Mutations in the gene could interfere with the depolarization process of retinal cells, as well as in the dental biomineralization process. We also show that mutations localized to the transmembrane domain of this protein result in more severe phenotypes of the syndrome, indicating an important function for this domain, probably as a transmembrane channel for metal transport. Jalili syndrome offers an example of how a single mutation in a gene is capable of affecting two independent traits by causing a defect in a single protein that carries out essentially the same function in two different tissue types. Given that 274 inherited disorders, almost exclusively reported in Arab families, have no defined genetic aetiologies as yet, and with the increasing trend of genome-wide association studies in the region, it is highly plausible that more conditions will be assumed to be manifestations of pleiotropy.
[ABSTRACT]   Full text not available  [PDF] [CITATIONS]
  4 441 37
The impact of child-rearing by maids on mother–child attachment
Abdulrahman Al-Matary, Jaffar Ali
May-August 2013, 6(2):197-204
DOI:10.7707/hmj.v6i2.119  
IntroductionThe objective of this study was to assess the perceived negative impact on mother–child attachment of raising children with the help of foreign maids, as practised in Arab Gulf countries. Materials and methods A descriptive cross-sectional study was conducted. A convenience sample was recruited from June 2010 to December 2010 from three tertiary hospitals and shopping centres. Five hundred questionnaires were distributed. Of these, 336 with complete data sets were analysed. The study was approved by the Institutional Review Board of the King Fahad Medical City. The analysed data were tabulated in the form of descriptive statistics. Results. Eighty per cent of households had a maid, but only 50% of mothers had careers. The proportion of babies who were not bottle-fed was 31.6%, with 15.7% exclusively breast-fed. Of the 52.8% of babies who were both breast- and bottle-fed, most were usually bottle-fed. The proportions of participants who reported high and low levels of mother–child attachment were 61.9% and 15.6% respectively. Although 22.6% declined to comment on this, questioning revealed a low level of mother–child attachment in this group, and therefore low mother–child attachment totalled 38.2% (15.6% + 22.6%). In 45.2% of cases, mothers stated that bonding was not affected by the maid, whereas 30% stated that bonding was affected. Although 24.2% declined to express their view, further questioning confirmed their discomfort in answering this question; this suggested that they did perceive a lack of bonding, and therefore that this affected a total of 54.2% (24.2% + 30%) of households. Discussion Although only half of the mothers had careers, a larger proportion of households had maids, indicating an overdependence of mothers on domestic aides. The very low proportion of babies who were exclusively breast-fed would suggest that mother–child bonding was affected in a large proportion of households that bottle-fed. However, about two-thirds of the mothers claimed high levels of mother–child bonding, whereas only one-sixth felt that bonding was adversely affected. The remainder were reluctant to discuss this point, suggesting that the problem of low levels of mother–child bonding exists. The study found that almost half of mother–child bonding relationships could be impaired by the presence of maids. Conclusion. This study indicates that mother–child attachment is adversely affected by the presence of maids, which could prove detrimental to the psychosocial development of affected children and the population of the Gulf Cooperation Council countries in the long term. Family-friendly work policies for mothers and education on responsible parenting are recommended.
[ABSTRACT]   Full text not available  [PDF] [CITATIONS]
  2 275 56
REVIEW ARTICLE
Literature review of small cell carcinoma of the urinary bladder
Anthony Kodzo-Grey Venyo, Douglas John Lindsay Maloney
May-August 2013, 6(2):149-162
DOI:10.7707/hmj.v6i2.225  
Small cell carcinoma of the urinary bladder is a rare tumour that resembles small cell carcinoma in the lung and elsewhere. Because of its rarity, practitioners may not be familiar with the biological behaviour of this tumour. The aim of this article is to review the literature on small cell carcinoma of the urinary bladder. Various internet search engines were used to explore the literature on small cell carcinoma of the urinary bladder including Google, Google Scholar, UpToDate, Pub Med and Educus. About 42 references were selected as the basis for the literature review. Small cell carcinoma of the urinary bladder is an aggressive tumour that typically presents with advanced or disseminated disease. This is a rare disease, accounting for only 0.5–1.0% of all bladder malignancies. Affected individuals show no age, sex or clinical differences from those with the typical type of urothelial carcinoma. Some cases of small cell carcinoma of the urinary bladder arise from urothelial carcinoma in situ while others arise from totipotent stem cells in the submucosa. The tumours are usually large polypoid masses that can occur anywhere in the bladder. Microscopically, the tumours appear as loosely cohesive sheets, or nests, of small to intermediate-sized cells with minimal cytoplasm, hyperchromatic nuclei, stippled or coarsely granular chromatin, indistinct nucleoli and no nuclear overlapping. Mitotic activity and necrosis are common and the tumours may co-exist with other forms of in situ, or invasive, carcinoma. Radical cystectomy is the main treatment for small cell carcinoma of the urinary bladder, unless metastatic disease is present, followed by systemic treatment. Response to chemotherapy is good, similar to treatment for small cell carcinoma of the lung, but the overall prognosis remains poor. There is no consensus regarding treatment of small cell carcinoma of the urinary bladder although general recommendations for the approach to treatment of this aggressive disease have been suggested.
[ABSTRACT]   Full text not available  [PDF] [CITATIONS]
  1 179 21
CASE REPORTS
Birth of a healthy boy after fertilization of a cryopreserved oocyte and testicular spermatozoon followed by preimplantation genetic screening
Hena Zaheer, Mohammed Elkalyoubi, Wael Ismail Madkour, Maise Al Adham, Awatif Albahar
May-August 2013, 6(2):241-246
DOI:10.7707/hmj.v6i2.193  
Full text not available  [PDF]
  - 107 15
Obesity surgery can be life saving
Sangram Jadhav, Sanjay Borude
May-August 2013, 6(2):247-250
DOI:10.7707/hmj.v6i2.228  
An 11-month-old female, who was born to consanguineous parents, weighed 19 kg at the time of referral from the Endocrine Department of Topiwala National Medical College and Nair Hospital to the Obesity Surgery Clinic for consideration for bariatric surgery. The patient had been admitted to the Endocrine Department of Topiwala National Medical College and Nair Hospital by her parents at the age of 2 months. The parents had lost their elder child at the age of 18 months and weighing 22 kg. The only chance of survival for the patient was to perform laparoscopic sleeve gastrectomy.
[ABSTRACT]   Full text not available  [PDF]
  - 180 17
Partial molar pregnancy resulting in a healthy newborn
Nawal M Hubaishi, Fatima Cherifi, Wafa F Mohsen, Amina Karami Binashoor, Saba Yehya Al Sayari, Nargis Mehdipour
May-August 2013, 6(2):251-254
DOI:10.7707/hmj.v6i2.142  
This article reviews a rare case of partial placental molar pregnancy resulting in a healthy newborn. A woman was admitted to the Department of Obstetric Gynecology at Dubai Hospital in the United Arab Emirates (UAE), where she subsequently gave birth to a healthy baby. In this multiparous patient, recurrent partial molar pregnancy was identified at 13 weeks by ultrasonography, which showed focal placental changes. However, the patient refused medical intervention and was kept under observation until 36 weeks, when a baby girl with a normal karyotype was born by normal vaginal delivery. There were no maternal complications. Partial molar pregnancy resulting in a live and healthy baby is rare and usually associated with numerous maternal complications, which were not present in this case. Complete evaluation of the placental tissue is important in cases where a live and healthy baby is delivered because molar changes may be focal and, therefore, cause unpredicted antenatal problems for the mother.
[ABSTRACT]   Full text not available  [PDF]
  - 153 16
Familial haemophagocytic lymphohistiocytosis
Ammar MH Shehadeh
May-August 2013, 6(2):255-258
DOI:10.7707/hmj.v6i2.240  
Haemophagocytic lymphohistiocytosis (HLH) is a rare, but potentially fatal, disease that occurs when normal histiocytes and lymphocytes become overactive and commonly occurs in infancy. Two forms of the disease have been described: primary and secondary. This article reports twins who were less than 2 years old at the time of presentation and who had clinical symptoms of primary (familial) HLH, which was diagnosed by a contributory pathological bone marrow test.
[ABSTRACT]   Full text not available  [PDF]
  - 169 15
Pleomorphic lipoleiomyoma of uterus
Farhana Zakaria
May-August 2013, 6(2):259-262
DOI:10.7707/hmj.v6i2.260  
Scattered adipocytes in an otherwise typical leiomyoma are a relatively common finding. A leiomyoma that contain a large number of adipocytes is called a lipoleiomyoma. We report a unique case of leiomyoma that presented with the following morphological features: mature spindled smooth muscle cells with and without nuclear atypia, epithelioid smooth muscle cells, mature adipose tissue, benign clear cells, coagulation necrosis. Only a few mitotic figures were noted. The rare occurrence of lipoleiomyomatous features in an otherwise pleomorphic leiomyoma prompted the report of the case below.
[ABSTRACT]   Full text not available  [PDF]
  - 157 14
Uterine rupture in a nulliparous woman at 26 weeks' gestation after laparoscopic myomectomy
Tasneem Rangwala, Abeer Ammar, Nadia Sawalhi
May-August 2013, 6(2):263-266
DOI:10.7707/hmj.v6i2.253  
Uterine scar dehiscence following laparoscopic myomectomy is very rare. We present a case of a nulliparous woman who was pregnant with twins and who had undergone laparoscopic excision of a small subserous myoma 2 years previously. The patient had subsequently developed a uterine rupture at 26 weeks' gestation; however, this was not initially suspected as the cause of the patient's abdominal pain owing to the rarity of this event. All pregnant patients who have a history of laparoscopic myomectomy, superficial or deep, should be closely monitored throughout pregnancy and uterine dehiscence or rupture should be suspected if they present with abdominal pain.
[ABSTRACT]   Full text not available  [PDF]
  - 158 12
EDITORIAL
Prostate cancer
Christian Kratzik
May-August 2013, 6(2):113-114
DOI:10.7707/hmj.vX6i2.279  
Full text not available  [PDF]
  - 109 19
ORIGINAL RESEARCH ARTICLES
Improving the management of placenta praevia accreta
Khalid Saleh, Nawal M Hubaishi, Hena Zaheer, Fatima Cherifi, Ibtihaj Alanizi
May-August 2013, 6(2):185-190
DOI:10.7707/hmj.v6i2.163  
Objectives The aims of this study were to assess the incidence of placenta praevia accreta, to identify risk factors for this complication and to analyse sonographic findings and the outcomes of interventions. This should improve antenatal diagnosis and facilitate the introduction of a new protocol for conservative management of this condition. Materials and methods This is a retrospective and descriptive study, over a period of 30 months, of women who underwent a caesarean section (CS) owing to placenta praevia accreta within the Obstetrics and Gynaecology Department at Dubai Hospital, United Arab Emirates. During this time, all files were reviewed and parameters collected, including patients' profile, risk factors, interventions, complications, blood loss, blood transfusion and length of hospitalization. Results. There were 11 cases of placenta praevia accreta (1 in 909 births). Two major risk factors were identified: the presence of a pre-existing uterine scar and previous occurrence of placenta praevia. Ultrasound findings were of limited use in reaching a diagnosis, resulting in 7 of these 11 patients requiring emergency intrapartum hysterectomy. Two had bladder injuries with blood loss of 2.9 l, and most of the patients required massive transfusion. The mean hospital stay was 7.1 days. The results were compared with those reported in the literature. Conclusions Previous placenta praevia and previous CS delivery are associated with placenta accreta, and result in an increased risk of morbidity and mortality. A key priority must be the introduction of a new protocol to include leaving the placenta in situ, particularly in women who wish to become pregnant again in the future.
[ABSTRACT]   Full text not available  [PDF]
  - 171 24
Quantitative analysis of mercury burden in the wastewater released from dental clinics in the United Arab Emirates
Sausan Al Kawas
May-August 2013, 6(2):191-196
DOI:10.7707/hmj.v6i2.118  
Amalgam waste from dental clinics is a significant source of mercury released into the environment when it is washed down a drain or disposed of improperly. Mercury is of particular concern because of its potential adverse effects on humans and the environment. As a consequence, several measures have been adopted by dental clinics worldwide to reduce mercury discharge into the environment. The aim of this study was to quantitatively asses the mercury burden in the wastewater discharged from some dental clinics in the United Arab Emirates using a cold-vapour atomic absorption spectrometry technique. Wastewater samples were collected from 28 public clinics at Sharjah and Abu Dhabi over a period of 10–14 days. The average concentration of mercury in all samples was 317.7 μg/l, with a standard deviation of 379.7 μg/l and a range from below the method detection limit (MDL) to 1535.2 μg/l. The results show some variation in mercury concentrations between samples, depending on the type and nature of dental operations undertaken at the specific clinic from which each sample originated. Most of the wastewater released from dental clinics in the study area contains concentrations of mercury which, although lower than levels reported elsewhere in the literature, are unacceptable according to local and international environmental standards. This implies that such wastewater should not be discharged without adequate pretreatment in order to reduce mercury pollution in the environment.
[ABSTRACT]   Full text not available  [PDF]
  - 166 19
How many renal colic patients undergo the recommended computed tomography? The Pennine Acute Trust Audit
William Evans, Helen Pollitt, Anthony Kodzo-Grey Venyo
May-August 2013, 6(2):205-208
DOI:10.7707/hmj.v6i2.208  
Non-contrast computed tomography (NCCT) is recommended by the British Association of Urological Surgeons (BAUS) guidelines for suspected renal calculi as this form of imaging offers kidney stone identification in > 99% of cases. We used the picture archiving and communications system (PACS) and automated letter systems to determine how many of the 144 patients admitted to the surgical triage unit (STU) at North Manchester General Hospital over the course of 14 months did in fact have renal colic, which radiological investigations were performed, how many patients with suspected renal colic underwent NCCT within 24 hours or 48 hours and how many underwent intervention. We found that only 19.8% of patients underwent NCCT within 24 hours and 22.9% within 24–48 hours. However, only three patients (3.12%) required an intervention related to this presentation. These low rates of intervention support the conclusions of other authors who believe that a combination of ultrasound and abdominal radiography in cases of suspected renal colic may be preferable to NCCT, which is costly and potentially harmful.
[ABSTRACT]   Full text not available  [PDF]
  - 181 15
Prenatal screening for fetal aneuploidies during the first and second trimester of pregnancy
Shiefa Sequeira, Shweta Uppal
May-August 2013, 6(2):209-220
DOI:10.7707/hmj.v6i2.224  
Prenatal screening for chromosomal defects during the first and second trimesters of pregnancy has become an established part of obstetric practice in many countries. The goal of current maternal serum screening programmes is to identify women who are at an increased risk of having a baby affected with Down syndrome (trisomy 21), Edwards syndrome (trisomy 18) or neural tube defects and who will benefit from such diagnostic tests. The most commonly used test for genetic diagnosis is amniocentesis; however, the rate of spontaneous fetal loss caused by this test averages at about 1 in every 200 procedures. Because of this risk, serum analyte testing has become an important and non-invasive first step in detecting patients at risk of carrying a child with congenital abnormalities. The non-invasive screening options which are currently available to patients include combining maternal age with one of the following: first-trimester serum screening [nuchal translucency (NT) and maternal serum biochemistry markers]; second-trimester serum screening (maternal serum biochemistry markers such as the triple test and the quadruple test); or the two-step integrated screening, which comprises first- and second-trimester serum screening with or without NT.
[ABSTRACT]   Full text not available  [PDF]
  - 185 25
Respiratory distress syndrome in preterm neonates of Lahore
Iftikhar Ejaz, Mumtaz Ali Bharo, Mehwish Anwer
May-August 2013, 6(2):221-226
DOI:10.7707/hmj.v6i2.233  
Compromised health facilities in developing countries often result in inadequate care for both mothers and their newborns. Consequently, a large number of neonates who are born prematurely with serious prepartum difficulties develop additional postpartum complications. Respiratory distress syndrome (RDS) in infants is a complex pulmonary state in which the lungs are not properly developed and therefore produce very little surfactant, resulting in morbidity of many preterm newborns. The present study investigated the frequency of RDS in neonates born at various gestational ages and of various birthweights. Out of 180 subjects, 50 (27.8%) developed RDS, the diagnosis of which was based on radiological findings and symptoms such as tachypnoea, nasal flaring and central cyanosis. The frequency of RDS is inversely, and significantly, associated with both gestational age and birthweight, which were found to be good predictors of the likelihood of a newborn developing RDS. Preterm newborns of low birthweight have a higher risk of developing RDS than full-term newborns of heavier birthweight. In light of these observations, proper management strategies should be devised for the assessment and treatment of preterm neonates with, or without, RDS.
[ABSTRACT]   Full text not available  [PDF]
  - 182 19
Respiratory diseases burden in the United Arab Emirates
Bassam H Mahboub, Seemin Afshan Shiraz, Amna Hassan, Arif Noor Mohammad, Muzaffar Iqbal, Mayank Vats, Jamal Abdul Razak, Bassel Safareni, Ashraf al Zaabi, Mohamad Al Sairi
May-August 2013, 6(2):227-232
DOI:10.7707/hmj.v6i2.251  
Respiratory diseases affect individuals worldwide and United Arab Emirates (UAE) is no exception. The burden of respiratory diseases is varied, and over the past two decades several studies have been carried out across UAE to estimate the load of respiratory diseases in the area and compare this with the international respiratory disease burden. The purpose of the present study was to compile the results of studies conducted in UAE in order to obtain an overview of the situation in this area. Comparison of the respiratory disease status in UAE and internationally will improve our knowledge about the situation, which will help us to implement strategies for improved respiratory care and respiratory disease outcome at a reasonable cost.
[ABSTRACT]   Full text not available  [PDF]
  - 226 15
REVIEW ARTICLE
Asymptomatic bacteriuria and urinary tract infections in pregnancy – a review of the literature
Anthony Kodzo-Grey Venyo
May-August 2013, 6(2):163-176
DOI:10.7707/hmj.v6i2.209  
The approach to the management of asymptomatic bacteriuria (AB) and urinary tract infections (UTIs) in pregnancy, including the choice of antibiotics, is not always straightforward. The aim of this article is to review the literature on AB and UTI in pregnancy and to discuss the findings. Various internet search engines were used to identify references regarding pregnancy-associated AB and UTI, which formed a framework for the literature review. Both conditions were found to be common in pregnancy. Pregnancy-associated UTI is defined as either a lower urinary tract infection (acute cystitis) or an upper urinary tract infection (acute pyelonephritis). The approach to the management of pregnancy-associated AB and UTI presents a complex issue, including the choice of antibiotics. UTIs occur when there are at least 100 000 organisms present per ml of urine in an asymptomatic patient, or more than 100 organisms per ml of urine with accompanying pyuria (more than seven white blood cells per ml in a symptomatic patient). A diagnosis of UTI requires a positive culture and identification of the pathogen, especially in patients with vague symptoms. UTIs are associated with risks to both the mother and the fetus, including pyelonephritis, preterm birth, low birthweight and increased risk of perinatal mortality. AB occurs when the bacterial count is greater than 100 000 organisms per ml in two consecutive samples of urine and in the absence of declared symptoms. If AB remains untreated during pregnancy, the risk of developing cystitis is 40% and the risk of developing pyelonephritis is 25–30%. The tendency for AB to progress to pyelonephritis is higher in pregnant women than in non-pregnant women and is associated with an increased risk of preterm birth, low birthweight and perinatal mortality. Appropriate antibiotics are recommended for both pregnant and non-pregnant women. Short-term courses have been recommended to minimize antimicrobial exposure to the fetus. The prognosis of the majority of pregnant women with UTI or AB during pregnancy is good. Most long-term sequelae are due to complications associated with septic shock, respiratory failure or hypotensive hypoxia with extreme gangrene. UTIs associated with pregnancy have few direct sequelae in view of the fact that fetal bloodstream infection is rare; nevertheless, uterine hypoperfusion due to maternal dehydration, maternal anaemia and direct bacterial endotoxin damage to the placental vasculature may result in fetal cerebral hypoperfusion. Untreated upper UTIs in pregnant women are associated with low birthweight, prematurity, premature labour, hypertension, pre-eclampsia, maternal anaemia and amnionitis. UTIs which occur during pregnancy are associated with intrauterine growth retardation, pre-eclampsia, preterm delivery and caesarean delivery. In order to avoid or minimize complications that may be associated with AB and UTI during pregnancy, both should be appropriately treated. Several antibiotic treatments are available and details of the antibiotic therapies are discussed below.
[ABSTRACT]   Full text not available  [PDF]
  - 177 16
Chronic neuropathic pain management – a review article
Alhan S Khazaal
May-August 2013, 6(2):177-184
DOI:10.7707/hmj.v6i2.239  
Chronic neuropathic pain (NEP) is commonly seen in clinical practice and represents a challenge to patients as well as clinicians. Pain is a complex sensory modality, resulting from the physiological activation of nociceptors that trigger a behavioural process to protect the individual from any existing, or further, tissue damage. Conditions that are frequently associated with NEP can be classified into two main groups: first, conditions that cause damage to the central nervous system (CNS), such as cortical and subcortical strokes; and, secondly, conditions that cause damage to the peripheral nervous system (PNS) such as ischaemic neuropathy, nerve root compression and phantom pain. There are multiple theories and pathophysiological processes underlying NEP; both basic and human research indicates that a lesion of afferent pathways is necessary for development of NEP. Furthermore, data clearly indicate that several mechanisms can lead to NEP and many of these mechanisms do not depend on the cause of the disease. The main mechanisms for the development NEP are ectopic nerve activity, upregulation of receptor proteins, central sensitization, inflammatory mechanism and disinhibition. The management of chronic NEP is challenging and the primary goal is to treat the pain and associated comorbidities, such as anxiety and depression. The secondary goals of treatment are to improve sleep, the ability to function normally and the overall quality of life. Tricyclic antidepressants (TCAs) are the most effective treatment in the management of NEP; however, serotonin–noradrenaline reuptake inhibitors (SNRIs), gabapentin and pregabalin, or lidocaine patches are also effective. Randomized controlled trials have reported the efficacy of opioids for different peripheral and central neuropathic disorders; however, using opioids for the treatment of NEP is not necessarily associated with a significant improvement in quality of life, psychological comorbidities or sleep disorders. In summary, management of NEP should be tailored to the individual patient on the basis of pain type(s), the causative disease, the relevant psychological factors and the interactions between the biological and psychosocial processes.
[ABSTRACT]   Full text not available  [PDF]
  - 164 18
Hepatic stellate cell – vitamin A-rich cells
SF Bennaser, NC Bird
May-August 2013, 6(2):141-148
DOI:10.7707/hmj.v6i2.200  
Quiescent hepatic stellate cells (HSCs) are characterized by their localization of perisinusoidal cells and their long cytoplasmic processes, extending both along and around the sinusoids as well as between the hepatocytes. These long cytoplasmic processes, which have numerous vitamin A-containing lipid droplets, are essential for the identification of HSCs in the quiescent phase. Glial fibrillary acidic protein (GFAP) (Abcam, Cambridge, UK) is another crucial marker for HSCs which may allow a distinction to be made between the HSCs and other fibroblastic liver cells. However, induction of alpha-smooth muscle actin (α-SMA) is the most reliable marker of stellate cell activation because it is absent from other resident hepatocytes in a normal or injured liver, with the exception of the smooth muscle cells surrounding large vessels where it is present. Desmin has been used as a typical marker for contractile stellate cells in rodent livers; however, its expression is unreliable in humans. Furthermore, HSCs' transdifferentiation to the active phase has been proven to rely on E-cadherin switching to N-cadherin during HSC activation. Significant evidence now exists to consider HSCs as the main matrix-producing cells in the process of the liver fibrosis. Liver injury, regardless of the aetiology, tumour growth and metastases will ultimately lead to activation of HSCs. Several studies have dissected the molecular mechanisms involved in liver fibrosis, most of which are intimately connected to HSCs. As a result, a number of key steps in the process of stellate cell activation and fibrogenesis have been identified as potential therapeutic targets that may be clinically useful in preventing, or treating, liver fibrosis.
[ABSTRACT]   Full text not available  [PDF]
  - 180 17
STATE-OF-THE-ART REVIEW
Testosterone and prostate cancer – new insights to help guide therapy
Christian Kratzik
May-August 2013, 6(2):115-120
DOI:10.7707/hmj.v6i2.276  
The role of androgen deprivation in slowing the effects of metastatic prostate cancer (PCa) has been recognized and established for more than 60 years. Nevertheless, the effect is only temporary, and virtually all cancers progress to a castration-resistant state. The discovery that late-stage PCa is driven by androgen receptor (AR) signalling led to it being described as ‛castration resistant‚ rather than ‛hormone refractory‚. During the castration-resistant stage, the PCa cell develops multiple cellular pathways to overcome androgen deprivation, including AR gene amplification, AR gene mutation, ligand-independent activation of the AR, involvement of coregulators and tumour stem cells as well as androgen production via a ‛backdoor pathway‚. New therapeutic options have been created to work against these survival abilities of the PCa cell. Abiraterone (Zytige®, Jannsen-Cilag, Neuss, Germany) inhibits the cytochrome P450 17 (CYP17) enzyme, which is essential for synthesis of testosterone from cholesterol, therefore affecting the traditional, as well as backdoor, pathways. Another promising drug, enzalutamide (Xtandi®, Astellas, Tokyo, Japan) (formerly known as MDV3100), is an AR signalling inhibitor that may be able to overcome the increased transcription of ARs. It has been well known for several years that, in a certain number of PCa patients, the application of testosterone results in a decrease in prostate-specific antigen (PSA). To maintain cellular genetic stability and viability, chromosomal DNA must be precisely replicated once and only once during each cell cycle. This is carried out through a process known as DNA replication licensing, in which a licensing factor is bound at the origin of replication. In PCa cells, the AR has a ‛gain of function‚ and acts as a licensing factor, which implies that the AR is degraded during mitosis because, without such degradation, the androgen-sensitive PCa cell will come to a subsequent S-phase arrest. This may be an explanation for the long-standing experimental paradox that testosterone can have a deleterious effect on PCa cells.
[ABSTRACT]   Full text not available  [PDF]
  - 173 15
Biomarkers for screening and early detection of prostate cancer
Malte Rieken, Shahrokh F Shariat
May-August 2013, 6(2):121-128
DOI:10.7707/hmj.v6i2.277  
Prostate cancer (PCa) represents a significant health burden and the high prevalence and natural course of the untreated disease make PCa ideal for screening and early detection. The aim of this review is to give an overview of the recent evidence on biomarkers for screening and early detection of PCa. A review of the current literature on prostate-specific antigen (PSA) and novel biomarkers in PCa diagnosis and screening was conducted using MEDLINE/PubMed to identify relevant publications. PSA is currently the main biomarker for PCa screening and diagnosis, and two out of three recent randomized controlled trials on PSA screening for PCa showed a 20–40% risk reduction of PCa-specific mortality in the screened group. In contrast, one study did not show any beneficial effect of PSA screening. Although each study had flaws, the study that reported no benefit from PSA screening had a high contamination rate in the control group and non-compliance in the screening group. However, PCa screening was associated with overdiagnosis, which led to overtreatment. Therefore, there is a need for novel biomarkers that are more specifically associated with PCa and its biological and clinical behaviour. Several such biomarkers are currently being investigated as an adjunct to PSA; however, none can currently replace PSA. Among novel biomarkers, PCa antigen 3 (PCA3) and TMPRSS2–ERG gene fusions appear to be most promising and, currently, PCA3 is reported as the more efficient diagnostic test in patients who have had a previous negative biopsy.
[ABSTRACT]   Full text not available  [PDF]
  - 181 15
Focal ablation of prostate cancer
Georg Schatzl
May-August 2013, 6(2):129-132
DOI:10.7707/hmj.v6i2.280  
The aim of the article was to evaluate the treatment potential for focal therapies of prostate cancer (PCa). A literature research was performed to evaluate efficiency of the minimally invasive methods of PCa treatment. The two treatment methods evaluated were high-intensity focused ultrasonography (HIFU) and cryoablation. There are few studies with sufficient long-term follow-up and follow-up criteria are very diverse. The increasing number of cryoablation and HIFU treatments in the last 10 years confirms the considerable demand for minimally invasive treatment for localized PCa. Focal ablation of PCa is an interesting treatment option for low-risk PCa, but there are not many opportunities for this treatment and the patient experience is often negative.
[ABSTRACT]   Full text not available  [PDF]
  - 177 18
The Martini-Clinic technique of open radical retropubic prostatectomy
Alexander Haese, Markus Graefen, Thorsten Schlomm, Thomas Steuber, Georg Salomon, Uwe Michl, Lars Budäus, Hans Heinzer, Hartwig Huland
May-August 2013, 6(2):133-140
DOI:10.7707/hmj.v6i2.281  
Despite the emergence of robotic approaches, the technique of open radical retropubic prostatectomy (RP) is still the predominant approach for surgical treatment of clinically localized prostate cancer in most clinics worldwide. The principles of this technique and its oncological efficacy were published decades ago; however, the surgery carried out today has undergone continuous refinements, reducing the morbidity rate and significantly improving postoperative functional outcomes such as urinary continence and erectile function. We report on the current technique of open nerve-sparing radical RP with data analysis to address the issues of urinary continence, potency, cancer control rates and perioperative morbidity. The analyses are based on 1875 patients who were treated with nerve-sparing RP in the Martini-Clinic. The key elements of open radical RP are a selective ligation of the dorsal vein complex and early release of the neurovascular bundles using a high anterior tension-free and energy-free intrafascial technique, intraoperative frozen section (NeuroSAFE technique) and full functional length urethral sphincter preparation (FFLU technique). During dissection of the urethra, the posterior insertion at Denonvilliers' fascia is preserved and remains in situ, and is selectively opened above the seminal vesicles. The later seminal vesicles are completely removed inside Denonvilliers' fascia and six muscle-sparing interrupted sutures are used for anastomosis. Functional and oncological outcome data were determined, which were prospectively collected using validated questionnaires and intraoperative and perioperative morbidity data were also evaluated. Patient age and the extent to which the nerve-sparing approach was influenced by urinary continence and potency. Overall, 97.4% of men less than 60 years of age, and 84.1% of men over 70 years, had complete urinary continence 1 year after nerve-sparing RP. In preoperative potent men, erections sufficient for intercourse were seen in 84–92% of patients who underwent bilateral nerve sparing and in 58.3–70% of men who underwent unilateral nerve sparing. Median blood loss was 590 ml (range 130–1800 ml) and the transfusion rate was 4.5%. Median operative time was 175 minutes (range 95–215 minutes). In organ-confined cancers, recurrence-free survival and cancer-specific survival at 10 years after RP were 87% and 98.3%, respectively. Open intrafascial nerve-sparing RP combines excellent long-term cancer control rates with superior functional outcome and a low morbidity.
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