The clinical outcomes of dapagliflozin in patients with acute heart failure: A randomized controlled trial (DAPA-RESPONSE-AHF).

AIMS: Dapagliflozin may confer additional decongestive and natriuretic benefits to patients with acute heart failure (AHF). Nonetheless, this hypothesis was not clinically examined. This study aimed primarily to investigate the effect of dapagliflozin on symptomatic relief in those patients. METHODS: This was a randomized, double-blind study that included 87 patients with AHF presenting with dyspnea. Within 24 h of admission, patients were randomized to receive either dapagliflozin (10 mg/day, N = 45) or placebo (N = 42) for 30 days. The primary outcome was the difference between the two groups in the area under the curve (AUC) of visual analogue scale (VAS) dyspnea score over the first 4 days. Secondary endpoints included urinary sodium (Na) after 2 h of randomization, percent change in NT-proBNP, cumulative urine output (UOP), and differences in mortality and hospital readmission rates. RESULTS: The results showed that dapagliflozin significantly reduced the AUC of VAS dyspnea score compared to placebo (3192.2 ± 1631.9 mm × h vs 4713.1 ± 1714.9 mm × h, P < 0.001). The relative change of NT-proBNP compared to its baseline was also larger with dapagliflozin (-34.89% vs -10.085%, P = 0.001). Additionally, higher cumulative UOP was found at day 4 (18600 ml in dapagliflozin vs 13700 in placebo, P = 0.031). Dapagliflozin decreased rehospitalization rates within 30 days after discharge, while it did not affect the spot urinary Na concentration, incidence of worsening of heart failure, or mortality rates. CONCLUSION: Dapagliflozin may provide symptomatic relief and improve diuresis in patients with AHF. Further studies are needed to confirm these findings. https://clinicaltrials.gov/study/NCT05406505.

Effect of cilostazol on preventing paclitaxel-induced neuropathy in patients with breast cancer: A randomized controlled trial.

STUDY OBJECTIVE: Paclitaxel-induced peripheral neuropathy is a significant clinical problem can markedly deteriorate patient's quality of life (QoL). Preclinical evidence exists about the preventive capacity of cilostazol against peripheral neuropathy. However, this hypothesis has not yet been clinically investigated. This proof-of-concept study evaluated the effect of cilostazol on the incidence of paclitaxel-induced peripheral neuropathy in patients with non-metastatic breast cancer. DESIGN: This is a parallel randomized placebo-controlled trial. SETTING: The Oncology Center at Mansoura University, Egypt. PATIENTS: Patients with breast cancer scheduled to receive paclitaxel 175 mg/m2 biweekly. INTERVENTIONS: Patients were randomized to either cilostazol group who received cilostazol tablets 100 mg BID, or to control group who received placebo instead. MEASUREMENTS: The primary endpoint was the incidence of paclitaxel-induced neuropathy evaluated through common terminology criteria for adverse event (NCI-CTCAE) version 4. Secondary endpoints included assessment of the patient's QoL by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT-GOG-NTx) subscale. Exploratory outcome measures included changes in serum levels of biomarkers namely nerve growth factor (NGF), and neurofilament light chain (NfL). MAIN RESULTS: The incidence of grade 2 and 3 peripheral neuropathies were significantly lower in the cilostazol group (40%) compared to the control group (86.7%) (p < 0.001). The incidence of clinically significant worsening in neuropathy-related QoL was higher in control group compared to the cilostazol group (p = 0.001). A higher percent increase from baseline in serum NGF was observed in the cilostazol group (p = 0.043). The circulating levels of NfL deemed comparable between the two arms at the end of the study (p = 0.593). CONCLUSION: Adjunctive use of cilostazol is as a novel option that might reduce the incidence of paclitaxel-induced peripheral neuropathy and improve the patients' QoL. Future larger clinical trials are warranted to confirm these findings.

Efficacy of Nondiuretic Pharmacotherapy for Improving the Treatment of Congestion in Patients with Acute Heart Failure: A Systematic Review of Randomised Controlled Trials.

Diuretic therapy is the mainstay during episodes of acute heart failure (AHF). Diuretic resistance is often encountered and poses a substantial challenge for clinicians. There is a lack of evidence on the optimal strategies to tackle this problem. This review aimed to compare the outcomes associated with congestion management based on a strategy of pharmacological nondiuretic-based regimens. The PubMed, Cochrane Library, Scopus, and ScienceDirect databases were systematically searched for all randomised controlled trials (RCTs) of adjuvant pharmacological treatments used during hospitalisation episodes of AHF patients. Congestion relief constitutes the main target in AHF; hence, only studies with efficacy indicators related to decongestion enhancement were included. The Cochrane risk-of-bias tool was used to evaluate the methodological quality of the included RCTs. Twenty-three studies were included; dyspnea relief constituted the critical efficacy endpoint in most included studies. However, substantial variations in dyspnea measurement were found. Tolvaptan and serelaxin were found to be promising options that might improve decongestion in AHF patients. However, further high-quality RCTs using a standardised approach to diuretic management, including dosing and monitoring strategies, are crucial to provide new insights and recommendations for managing heart failure in acute settings.

Author Correction: Thymoquinone therapy remediates elevated brain tissue inflammatory mediators induced by chronic administration of food preservatives.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Thymoquinone therapy remediates elevated brain tissue inflammatory mediators induced by chronic administration of food preservatives.

Continuous exposure to preservatives such as nitrite salts has deleterious effects on different organs. Meanwhile, Nigella sativa oil can remediate such organ dysfunction. Here, we studied the effect of consumption of thymoquinone (TQ); the main component of Nigella sativa oil on the brain damage induced by sodium nitrite. Forty adult male rats were daily given oral gavage of sodium nitrite (80 mg/kg) with or without thymoquinone (50 mg/kg). Oxidative stress, cytokines of inflammation, fibrotic elements and apoptotic markers in brain tissue were measured. Exposure to sodium nitrite (SN) resulted in increased levels of malondialdehyde, TGF-ß, c-reactive protein, NF-κB, TNF-α, IL-1ß and caspase-3 associated with reduced levels of glutathione, cytochrome c oxidase, Nrf2 and IL-10. However, exposure of rats' brain tissues to thymoquinone resulted ameliorated all these effects. In conclusion, thymoquinone remediates sodium nitrite-induced brain impairment through several mechanisms including attenuation of oxidative stress, retrieving the reduced concentration of glutathione, blocks elevated levels of pro-inflammatory cytokines, restores cytochrome c oxidase activity, and reducing the apoptosis markers in the brain tissues of rats.

Oestrogen receptors beta genotype in infertile Egyptian men with nonobstructive azoospermia.

In a prospective study, the polymorphism of oestrogen receptor ß gene was investigated in nonobstructive azoospermia patients. Ninety infertile patients with nonobstructive azoospermia diagnosed after two semen analysis, 2 weeks apart and negative testicular sperm extraction during intracytoplasmic sperm injection, and 60 fertile men as controls were enrolled in the study. Semen analysis, hormonal profile and allele-specific PCR reaction were performed to detect variants of the RsaI polymorphism of the oestrogen receptor ß gene for all patients and controls. The mean patient's age was significantly lower than the mean age of the controls (P < 0.05). There was a significant increase in the mean serum levels of FSH, LH, free testosterone and E2 and significant decrease in total testosterone in patients than controls (P < 0.05). In the patients, the frequency of the homozygous GG, heterozygous AG and homozygous AA genotype was 83.3%, 14.3% and 3.3% respectively, whereas their frequencies in the controls were 95%, 5% and 0% respectively (odds ratio 3.8). There is no significant correlation between ERß polymorphisms and patient's age or pituitary and sex hormones (P > 0.05). Our findings suggested that in Egyptian population, genetic mutation in ERß is associated with the risk of nonobstructive azoospermia.

Inflammation and psychotropic drugs: the relationship between C-reactive protein and antipsychotic drug levels.

RATIONALE: In psychiatric clinical practice, there is a need to identify psychotropic drugs whose metabolisms are prone to be altered with increased inflammatory activity in an individual patient. OBJECTIVES: The aim of this study was to find out whether elevated serum levels (≥5 mg/l) of C-reactive protein (CRP), an established laboratory marker of infection and inflammation, are associated with increased serum concentrations of the atypical antipsychotic drugs clozapine, quetiapine, and risperidone. METHODS: Therapeutic drug monitoring request forms of patients whose antipsychotic drug concentrations had been measured under conditions of normal (<5 mg/l) and pathological (>5 mg/l) levels of C-reactive protein were retrospectively screened. The serum concentrations in relation to the daily doses [concentration per dose (C/D) (ng/mL/mg)] and the metabolic ratios [ratio of concentrations (metabolite/drug)] were compared intraindividually by the Wilcoxon signed rank test. To the study effects of the intensity of infections on drug concentrations, C-reactive protein and C/D levels were submitted to Spearman's correlation analysis. RESULTS: Elevated levels of C-reactive protein were found in 105 patients. They were significantly associated with elevated values in C/D for clozapine (n = 33, P < 0.01) and risperidone (n = 40, P < 0.01). A trend for an increase was found for quetiapine (n = 32, P = 0.05). Median increases were 48.0 % (clozapine), 11.9 % (quetiapine), and 24.2 % (active moiety of risperidone), respectively. CONCLUSIONS: In patients who exhibit signs of inflammation or infection with increased C-reactive protein values during psychopharmacological treatment, especially under clozapine and risperidone, therapeutic drug monitoring is recommendable in order to minimize the risk of intoxications due to elevated drug concentrations.

Melperone but not bisoprolol or metoprolol is a clinically relevant inhibitor of CYP2D6: evidence from a therapeutic drug monitoring survey.

Cytochrome P450 enzymes (CYP) can be inhibited or induced by drugs, resulting in clinically significant drug-drug interactions that can cause unanticipated adverse reactions or therapeutic failures. The objective of the study was to analyze the in vivo inhibitory potential of the beta-blockers bisoprolol and metoprolol as well as the low-potency antipsychotic melperone on CYP2D6. By utilizing a large therapeutic drug monitoring database of 2874 samples, data from patients who had been treated with venlafaxine (VEN) either without (control group) or with a concomitant medication with bisoprolol, metoprolol or melperone were evaluated retrospectively to study the CYP2D6-catalyzed O-demethylation to O-desmethylvenlafaxine (ODVEN). Dose-adjusted serum levels (C/D) of VEN and ODVEN as well as the metabolic ratios (ODVEN/VEN) were computed for the four groups and compared using Kruskal-Wallis test. In total, 381 patients could be included for analysis. No significant difference was found in the median C/D (VEN), C/D (ODVEN) or C/D of the active moiety (VEN + ODVEN) in either the metoprolol (N = 103) or bisoprolol group (N = 101), compared to the control group (N = 108). In contrast, a significantly higher median C/D (VEN) (0.79 ng/ml/mg, range 0.13-5.73 ng/ml/mg) (P < 0.01) was found in the melperone group (N = 69), compared to the control group (0.46 ng/ml/mg, range 0.02-7.39 ng/ml/mg). A significant decrease (P < 0.01) was solely found in the median metabolic ratios of ODVEN/VEN between the melperone group (0.90, range 0.14-15.15), compared to the control group (2.39, range 0.06-15.31). The results of this study provided evidence that melperone but not bisoprolol or metoprolol has a clinically relevant inhibitory potential on CYP2D6.

Adherence to medication among outpatient adolescents with epilepsy.

BACKGROUND AND OBJECTIVE: The promotion of medication adherence is considered as an integral component of pharmaceutical care practice and patient healthcare. An approach which focuses on the choice and dose of antiepileptic drug will have limited success without medication adherence. This study sought to assess medication adherence for improvement among adolescents who are suffering from epilepsy. METHODS: A total of 116 patients affected with idiopathic epilepsy and fulfilled the inclusion criteria were recruited in the current study. Adherence to the treatment was evaluated during patients' hospitalization in the Department of Neurology at Riyadh National Hospital, Riyadh, Saudi Arabia, between December 2011 and January 2014. The medication adherence has been assessed during semi-structured interviews with each patient and/or his parents using a multiple choice graded questionnaire. RESULTS: From the selected group of patients, only 94 patients (81.0%) fulfilled the inclusion criteria within the study period. Thirty-six of respondents (38.3%) were non adherent to antiepileptic treatment. No statistical differences were found between males and females regarding their ages, age at diagnosis of epilepsy, mother age, epilepsy duration, family numbers, number of poor-adherents or seizure frequency. The most important factors that were significantly affecting patients' adherence to the prescribed medications were age of mother, family number, number of administered drugs, the stability of parents' marriage, family support, and seizure frequency as well as the regularity of the relationship between patients and their healthcare providers. Forgetfulness was the most common cause of non-adherence among this group of patients followed by inability to obtain medication and fear from side effects of drugs. Our results revealed also that the number of patients who felt to be stigmatized is significantly more in non-adherent group as compared to patients with a strong sense of normality (P < 0.05). A positive relationship between adherence and the necessity and benefit scales at which patients have a stronger belief in the necessity of medication for controlling illness was associated with good adherence. CONCLUSION: The assessment of medication adherence among epileptic patients should be a routine part of the management process to improve the health care and quality of lives of those patients.

Effects of chronic tramadol administration on testicular tissue in rats: an experimental study.

UNLABELLED: In a prospective experimental study, the effects of chronic tramadol administration on gonadotrophic and sex hormones, histopathological and morphometrical alterations in rat testicular tissue were investigated in a laboratory setting. Tramadol was given alone to adult male albino rats. Gonadotrophic and serum sex hormone levels were measured and testicular pathological and morphometric changes were observed in treated vs. CONTROL GROUP: After 30 days of treatment, tramadol induced a decrease in LH, FSH and testosterone serum levels. Histologically, degenerative changes in the seminiferous tubules were observed. They showed shrinkage, separation of tubular basement membrane, disorganisation and vacuolisation of spermatogenic layers. Morphometric analysis revealed significant decrease in the mean values of the tubular diameter and epithelial height. Ultrastructural abnormalities were detected in all cells of spermatogenic lineage in addition to the appearance of apoptotic cells. Sertoli cell vacuolation, huge lipid droplets and disrupted Sertoli cell junctions were observed. Leydig cells showed euchromatic nuclei and dilated smooth endoplasmic reticulum. In view of these findings, it is concluded that tramadol induces alterations in sex hormonal levels in conjunction with disruption of the normal histological structure of rat testis. This might lead to the risk of male infertility. Therefore, tramadol should be used with caution with appropriate dose monitoring.

Protective effects of arjunolic acid against cardiac toxicity induced by oral sodium nitrite: effects on cytokine balance and apoptosis.

AIMS: Sodium nitrite, a preservative used in meat products, helps in the production of free radicals, leading to increased lipid peroxidation, which plays a vital role in posing toxic effects in different body organs. On the other hand, arjunolic acid possesses antioxidant properties and plays protective roles against chemically induced organ pathophysiology. We investigated the effect of sodium nitrite on cardiac tissue in rats on the inflammatory cytokine balance and the type of induced apoptosis, and we analyzed the protective role of arjunolic acid. MAIN METHODS: Sixty adult male Sprague-Dawley rats were injected with 80mg/kg sodium nitrite in the presence/absence of arjunolic acid (100 and 200mg/kg). Cardiac pro-inflammatory cytokines (TNF-α and IL-1ß), c-reactive protein (CRP) and anti-inflammatory cytokines (IL-4 and IL-10) were measured by ELISA. Cardiac mitochondrial activity (cytochrome-C-oxidase), JNK activation and apoptosis (caspase-3, caspase-8 and caspase-9) were assessed. KEY FINDINGS: Sodium nitrite resulted in increased TNF-α (1.6-fold), IL-1ß (3.7-fold) and CRP (2.4-fold) levels accompanied by 52%, 59% and 40% reductions in IL-10, IL-4 and cytochrome-C-oxidase, respectively, as well as enhanced JNK, caspase-3, caspase-8 and caspase-9 activities. Arjunolic acid markedly ameliorated these effects. SIGNIFICANCE: Arjunolic acid attenuated sodium nitrite-induced cardiac damage in rats and restored the normal balance between pro- and anti-inflammatory cytokines. Moreover, arjunolic acid protected cardiac tissues from both extrinsic and intrinsic cell death pathways.

Xanthoma disseminatum: a progressive case with multisystem involvement.

Xanthoma disseminatum (XD) is a rare, benign, non-Langerhans cell histiocytic disorder. The pathogenesis is not clear. It manifests with multiple, grouped, red-brown to yellow papules and nodules involving the skin, mucous membranes, and internal organs. We present a case of progressive XD in a 10-year-old male child. The patient presented with progressive, bilateral and symmetrical, reddish-brown, coalescent papules on the neck, around both eyes and all over his trunk and extremities. Skin lesions were accompanied by blurred vision and hoarseness of voice. Examination revealed xanthomatous infiltration of cornea, oral, pharyngeal, and laryngeal mucosae. The patient had diabetes insipidus that was diagnosed 2 years before the appearance of skin lesions. Medical treatment with corticosteroids (20 mg/day) and azathioprine (2 mg/kg/day) did not stop the disease progression.

Pachydictyols B and C: new diterpenes from Dictyota dichotoma Hudson.

Two new diterpenoids, pachydictyol B (1a/1b) and C (2), were isolated from the dichloromethane extract of the marine brown alga, Dictyota dichotoma, collected from the Red Sea coast of Egypt, along with the known metabolites, pachydictyol A (3a), dictyol E (4), cis-africanan-1α-ol (5a), fucosterol (6), tetrahydrothiophen-1,1-dioxide and poly-ß-hydroxybutyric acid. GC-MS analysis of the nonpolar fractions also indicated the presence of ß-bourbonene and nonanal, along with three hydrocarbons and five fatty acids or their simple derivatives, respectively. GC-MS analysis of the unsaponifiable algal petroleum ether extract revealed the presence of a further eight compounds, among them 2,2,6,7-tetramethyl-10-oxatricyclo[4.3.0.1(1,7)]decan-5-one (7), N-(4-bromo-n-butyl)-pipe ridin-2-one (8) and tert-hexadecanethiol. Structures 1-6 were assigned by 1D and 2D NMR, mass spectra (EI, CI, HREI and HRESI) and by comparison with data from related structures. The crude algal extract was potently active against the breast carcinoma tumor cell line, MCF7 (IC50 = 0.6 µg mL⁻¹); pachydictyol B (1a) and dictyol E (4) showed weak antimicrobial properties, and the other compounds were inactive. Pachydictyols B (1a) and C (2) demonstrated a weak and unselective cytotoxicity against twelve human tumor cell lines with a mean IC50 of >30.0 µM.

Q-angle, Pelvic width, and Intercondylar notch width as predictors of knee injuries in women soccer players in South Africa.

OBJECTIVE: To investigate the association between the three anatomical factors of Q-angle (QA), pelvic width (PW) and Intercondylar notch width (INW) and knee injuries among the U-23 female soccer players of South Africa METHODS: The study is a case-control prospective study design. Twenty four U-23 women soccer players of the South African team were purposively chosen to participate in this study. Participants were divided into two groups: group 1 (Case) was those with knee injuries, while those without injuries were in group-2 (Control). PW and INW were measured after X-rays of the hip were taken while the QA was measured manually with the goniomenter. Association between anatomical factors and knee injuries were tested with ANOVA. RESULTS: Q-angle ranged from 14° to 18° for both injured and non injured groups. PW was between 24 -29 cm for both injured and non injured groups. INW was between 1.3mm and 2.8mm for the right and between 1.4mm and 2.5mm for the left notch for the injured group, while INW for the right and left of the non injured group were between 1.7 mm to 2.1 mm and 1.8 mm to 2.1 mm, respectively No significant association between knee injuries and each of the anatomical factors was found QA (p= 0.74), PW (p=0.34), INW (right and left respectively) (p=0.142 & p=0.089). CONCLUSION: The three anatomical factors of QA, PW and INW could not be used to predict knee injuries amongst the U-23 female players in South Africa.

Fish oil improves lipid metabolism and ameliorates inflammation in patients with metabolic syndrome: impact of nonalcoholic fatty liver disease.

CONTEXT: Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent in Egypt, in parallel with increasing obesity. NAFLD can lead to liver inflammation, fibrosis and cirrhosis. NAFLD appears tightly linked with metabolic syndrome (MetS). OBJECTIVE: Examine the impact of dietary fish oil on human patients with MetS and NAFLD. MATERIALS AND METHODS: One hundred and forty patients were enrolled in the current study and classified into two groups: patients with both MetS and NAFLD and patients with MetS alone. Sixty-four patients were treated with daily supplementation of 2 g of fish oil for 6 months. Markers of hyperlipidemia and oxidative stress, hydrogen peroxide (H(2)O(2)) and malondialdhyde (MDA), as well as proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), were analyzed. RESULTS: Patients without fish oil exhibited significant increases in triglycerides (TGs), low-density lipoprotein (LDL), H(2)O(2) and MDA that were associated with significantly elevated TNF-α and IL-6 compared to controls. Furthermore, patients with both NAFLD and MetS showed significant increase in H(2)O(2), MDA, TNF-α and IL-6 levels compared with MetS group (p < 0.05). Treatment with fish oil reduced serum level of TG, LDL-cholesterol (LDL-C), H(2)O(2), MDA, TNF-α and IL-6 levels in patients and did not affect the control levels. DISCUSSION AND CONCLUSION: Patients with NAFLD had bad lipid profile through a mechanism that involved developed redox imbalance, characterized by boosted free-radical activity and lipid peroxidation enhancing the release of proinflammatory cytokines leading to increased MetS risk and liver damage. However, daily treatment of patients with fish oil for 6 months improved lipid profile and blocked the oxidative stress and cytokines release.

Type 2 Diabetes Mellitus-Induced Hyperglycemia in Patients with NAFLD and Normal LFTs: Relationship to Lipid Profile, Oxidative Stress and Pro-Inflammatory Cytokines.

Type 2 diabetes mellitus is associated with dyslipdemia, insulin resistance and non alcoholic fatty liver disease. The purpose of the current study was to assess whether type 2 diabetes mellitus-induced hyperglycemia has an effect on the lipid profile and release of oxidative stress markers and inflammatory mediators in patients with non alcoholic fatty liver disease and normal liver function tests which may in turn lead to enhancing the pathogenicity of this liver disease. For this purpose, one hundred and five outpatients, matched in age and weight, were classified into two groups: the first group consisted of patients with non alcoholic fatty liver disease and the second group consisted of patients with non alcoholic fatty liver disease in conjunction with hyperglycemia due to the presence of type 2 diabetes mellitus. In all patients, lipid profile, oxidative stress, and inflammatory mediators were assessed by measuring serum concentrations of triglycerides, low density lipoprotein, hydrogen preroxide, malondialdehyde, tumor necrosis factor-alpha and interleukin-6, respectively. In the studied population, it was found that the presence of type 2 diabetes mellitus-induced hyperglycemia significantly impaired lipid profile, and significantly enhanced the formation of hydrogen preroxide and malondialdehyde as well as significantly increased the release of tumor necrosis factor-alpha and interleukin-6 in the second group of patients. In addition, plasma glucose level showed significant positive correlation with hydrogen peroxide, malondialdehyde, tumor necrosis factor-alpha and interleukin-6. From the previous results, it was concluded that the presence of type 2 diabetes mellitus-induced hyperglycemia results in significant increase in lipid profile, oxidative stress markers and inflammatory mediators in patients with non alcoholic fatty liver disease and normal liver function tests. For this reason, further research studies may be essential to evaluate the benefit of adding suitable antioxidant and anti-inflammatory drugs to the treatment regimen for this group of patients. In addition, regular monitoring of blood glucose levels and liver function tests should be advised to this category of patients to reduce liver fat deposition and avoid the development of non alcoholic steatohepatitis, cirrhosis or liver cancer and their related complications.

Measuring the rate of therapeutic adherence among outpatients with T2DM in Egypt.

BACKGROUND AND OBJECTIVE: The promotion of therapeutic adherence is considered as an integral component of pharmaceutical care practice and patient healthcare. It has been shown that despite effective methods of treatment, 50% of diabetic patients fail to achieve satisfactory glycemic control, which leads to accelerated development of complications and increased mortality. Clinical experience indicates that no improvement of metabolic control is possible without patients' adherence to medications. This study sought to examine the rate of medication adherence and different factors affecting it among Type 2 diabetic patients in Egypt. METHODS: A total of 226 Type 2 diabetic patients who fulfilled the inclusion criteria were recruited in the current study. Adherence to the treatment was evaluated during patients' hospitalization in the Outpatient Clinics of Internal Medicine Department at University of Mansoura, Egypt. The medication adherence has been assessed during a personal interview with each patient using a multiple-choice graded questionnaire. RESULTS: In the study population, the adherence rates to medication, dietary/exercise and appointment were observed to be suboptimal. The most important social factors that were significantly affecting adherence rate to the prescribed oral hypoglycemic agent(s) included marital status (P < 0.01), family support (P < 0.01), and socio-economical level (P < 0.01). Other patient factors that were significantly affecting therapeutic adherence were patient knowledge about the disease (P < 0.01), patients' beliefs and motivation about prescribed drugs (P < 0.01), and regularity of patients' self monitoring of blood glucose level (P < 0.01). Among drug factors which found to affect significantly the rate of medication adherence are the number of drugs taken (P < 0.05), complexity of drug regimen (P < 0.01), and the presence of drug side effects (P < 0.01). Economical factor played an equally important role. Direct and indirect care costs in relation to patients' income were significantly affecting the rate of adherence to medication (P < 0.01). CONCLUSIONS: An improvement with the adherence to oral hypoglycemic agent(s) may be achieved through continuing patient education about diabetes, improvement of patients' economical levels as well as a reduction in the cost of medication. Pharmaceutical companies have to be involved and pharmacists have to be payed for helping chronically ill patients to take their medicines correctly for improving clinical outcomes.

Telomerase activity, cytokeratin 20 and cytokeratin 19 in urine cells of bladder cancer patients.

AIM OF THE STUDY: This work aims to search for markers suitable for the screening of bladder cancer, which should be specific, sensitive, reproducible, non-invasive and at acceptable cost. PATIENTS AND METHODS: The study included 50 patients diagnosed as bladder cancer (35 TCC, 15 SCC) of different stages and grades, 30 patients with various urothelial diseases, besides 20 apparently healthy subjects of matched age and sex to the malignant group. A random midstream urine sample was collected in a sterile container for the determination of telomerase by RT-PCR, keratin 19 by ELSA CYFRA 21-1 IRMA kit, keratin 20 by RT-PCR and immunohistochemical staining, and urine cytology. RESULTS: For all parameters (telomerase, K19, K20 and cytology) the malignant group was significantly different from both the benign and the control groups. None of the four studied parameters was correlated to the stage of the disease, and when it comes to grade, only K19 showed a significant positive correlation with grade both in TCC and SCC. When ROC curves for all parameters were compared, K19 had the largest area under the curve, and then comes K20. CONCLUSION: K 19 may be used as a biological marker for the diagnosis of bladder cancer. K19 could not be used for differential diagnosis of different types of bladder cancer, meanwhile it could be a marker for differentiation that decreases in less differentiated tumors. As a tumor marker, K20 reflects inability to differentiate tumor type or grade in TCC, while in SCC of the bladder it is correlated with the grade. As a method, RT-PCR is superior to immunostaining for the detection of bladder cancer, meanwhile K20 immunohistochemistry (IHC) results were much better than urine cytology as a bladder cancer screening test. Haematuria and inflammation reduced the specificity of telomerase assay, which reduced its validity as a tumor marker of bladder cancer. K19 and K20 are the best candidates as screening tests for the diagnosis of bladder cancer, representing the highest sensitivity and specificity, beside the radiological and histopathology. Meanwhile, telomerase, although it was a sensitive enough marker, it reflected a high false positive rate.

Chronic subdural haematoma treated by craniotomy, durectomy, outer membranectomy and subgaleal suction drainage. Personal experience in 39 patients.

According to the CT and MRI appearances, 39 chronic subdural haematoma (CSDH) patients were suspected of having solid clots and/or a high likelihood of loculation. Craniotomy was planned from the start. Beside the better exposure, excision of the dura and outer membrane, assumed to be the source of haematoma fluid, this is an additional step to minimize the incidence of significant recollection. There were no additional operative or postoperative cranial and/or systemic complications when compared with other minor procedures. Two patients (5%) required once percutaneous tapping and aspiration. Accordingly, if a case is considered to be better managed with craniotomy, durectomy and outer membranectomy this is an easy and safe technique with minimal incidence of recollection, morbidity and mortality.

The role of pelvic traction in the management of primary monosymptomatic nocturnal enuresis.

OBJECTIVE: To determine whether pelvic traction is beneficial in children with primary nocturnal enuresis. PATIENTS AND METHODS: There can be disproportionate growth between the spinal column and neural tube in prepubertal children. The normal elongation of the vertebral column in children during sleep could stretch the filum terminale and nerve roots, representing a minor degree of tethering that affects neural function and contributes to nocturnal enuresis. Pelvic traction induces a similar or more intense stretch while a patient is fully awake (and able to control their bladder). Releasing the potential tethering in this way, combined with conditioning therapy, could be beneficial. Fifty patients (aged 7-17 years) with monosymptomatic primary nocturnal enuresis were evaluated in a prospective study. All had 10 sessions of pelvic traction applied over 4 weeks and were followed up for 3 months afterward; no other medications were given. RESULTS: All patients had fewer wet nights, with variable degrees of success (20-80%) during and 3 months after traction. CONCLUSION: Pelvic traction is a safe, simple, economic and effective treatment for primary monosymptomatic nocturnal enuresis.