Cystic fibrosis detection in high-risk Egyptian children and CFTR mutation analysis.

BACKGROUND: Knowledge about Cystic Fibrosis (CF) in Egypt is very limited. The objective of this study was to screen for CF in Egyptian children with suggestive clinical features and to identify causative genetic mutations. METHODS: Sixty-one patients from the Chest Unit, Cairo University Children's Hospital, Egypt, were included. Subjects presented with persistent or recurrent respiratory symptoms, failure to thrive, diarrhea and/or steatorrhea and unexplained persistent jaundice. Patients were screened using the CF Indicatortrade mark sweat test system (PolyChrome Medical, Inc., Brooklyn Center, MN). A quantitative sweat testing was conducted on 10 of the 12 positive patients. Seven probands and one sibling underwent molecular analysis by direct DNA sequencing of the coding region and of the intronic sequences adjacent to the 27 exons of the CFTR gene. RESULTS: Of 61 patients, 12 (20%) had positive sweat chloride screening. Ten of the 12 patients underwent quantitative sweat testing and were positive. Eight CFTR sequence changes were identified in seven affected probands and two were confirmed in one sibling by direct DNA sequencing. CONCLUSION: The study results suggest that CF is more common in Egypt than previously anticipated. Larger studies are warranted to identify the incidence, molecular basis and clinical pattern of CF in the Egyptian population.     

Differentiation of murine male germ cells to spermatozoa in a soft agar culture system

Establishment of an in vitro system that allows the development of testicular germ cells to sperm will be valuable for studies of spermatogenesis and future treatments for male infertility. In the present study, we developed in vitro culture conditions using three-dimensional agar culture system (SACS), which has the capacity to induce testicular germ cells to reach the final stages of spermatogenesis, including spermatozoa generation. Seminiferous tubules from testes of 7-day-old mice were enzymatically dissociated, and intratubular cells were cultured in the upper layer of the SACS in RPMI medium supplemented with fetal calf serum (FCS). The lower layer of the SACS contained only RPMI medium supplemented with FCS. Colonies in the upper layer were isolated after 14 and 28 days of culture and were classified according to their size. Immunofluorescence and real-time PCR were used to analyse specific markers expressed in undifferentiated and differentiated spermatogonia (Vasa, Dazl, OCT-4, C-Kit, GFR-α-1, CD9 and α-6-integrin), meiotic cells (LDH, Crem-1 and Boule) and post-meiotic cells (Protamine-1, Acrosin and SP-10). Our results reveal that it is possible to induce mouse testicular pre-meiotic germ cell expansion and induce their differentiation to spermatozoa in SACS. The spermatozoa showed normal morphology and contained acrosomes. Thus, our results demonstrate that SACS could be used as a novel in vitro system for the maturation of pre-meiotic mouse germ cells to post-meiotic stages and morphologically-normal spermatozoa.     

Late spontaneous recanalization of a symptomatically occluded internal carotid artery two years after extra-intracranial bypass. Case report and review of the literature

Spontaneous recanalization of the internal carotid artery (ICA) is rarely observed. Mainly case reports are published. Most often early recanalization occurs within days or weeks and only a few cases of late recanalization months or years after detected occlusion are reported. Symptomatic bilateral ICA occlusion is regarded as an acceptable indication for extra-intracranial (EC-IC) bypass. The authors report on a case with bilateral symptomatic ICA occlusion and EC-IC bypass >2 years prior to detected spontaneous leftsided recanalization. Spontaneous recanalization unmasking a high degree ICA stenosis at the carotid bifurcation allowed a successful subsequent surgical recanalization in this patients. Mechanisms of early and late recanalization as well as treatment options are discussed.     

Impact of Calcium and Two Doses of Vitamin D on Bone Metabolism in the Elderly: A Randomized Controlled Trial

The optimal dose of vitamin D to optimize bone metabolism in the elderly is unclear. We tested the hypothesis that vitamin D, at a dose higher than recommended by the Institute of Medicine (IOM), has a beneficial effect on bone remodeling and mass. In this double‐blind trial we randomized 257 overweight elderly subjects to receive 1000 mg of elemental calcium citrate/day, and the daily equivalent of 3750 IU/day or 600 IU/day of vitamin D3 for 1 year. The subjects’ mean age was 71 ± 4 years, body mass index 30 ± 4 kg/m², 55% were women, and 222 completed the 12‐month follow‐up. Mean serum 25 hydroxyvitamin D (25OHD) was 20 ng/mL, and rose to 26 ng/mL in the low‐dose arm, and 36 ng/mL in the high‐dose arm, at 1 year (p < 0.05). Plasma parathyroid hormone, osteocalcin, and C‐terminal telopeptide (Cross Laps) levels decreased significantly by 20% to 22% in both arms, but there were no differences between the two groups for any variable, at 6 or 12 months, with the exception of serum calcitriol, which was higher in the high‐dose group at 12 months. Bone mineral density (BMD) increased significantly at the total hip and lumbar spine, but not the femoral neck, in both study arms, whereas subtotal body BMD increased in the high‐dose group only, at 1 year. However, there were no significant differences in percent change BMD between the two study arms at any skeletal site. Subjects with serum 25OHD <20 ng/mL and PTH level >76 pg/mL showed a trend for higher BMD increments at all skeletal sites, in the high‐dose group, that reached significance at the hip. Adverse events were comparable in the two study arms. This controlled trial shows little additional benefit in vitamin D supplementation at a dose exceeding the IOM recommendation of 600 IU/day on BMD and bone markers, in overweight elderly individuals. © 2017 American Society for Bone and Mineral Research.     

General anaesthesia vs. conscious sedation for transfemoral aortic valve implantation: a single UK centre before‐and‐after study

Reported data suggest that 99% of transfemoral, transcatheter aortic valve implantations in the UK are performed under general anaesthesia. This before‐and‐after study is the first UK comparison of conscious sedation vs. general anaesthesia for this procedure. Patients who underwent general anaesthesia received tracheal intubation, positive pressure ventilation, radial arterial and central venous access and urinary catheterisation. Anaesthesia was maintained with propofol or sevoflurane. Patients who received conscious sedation had a fascia iliaca and ilioinguinal nerve block and low‐dose remifentanil infusion, without invasive monitoring or urinary catheterisation. Recruitment took place between August 2012 and July 2015, with a 6‐month crossover period between November 2013 and June 2014. A total of 88 patients were analysed, evenly divided between the two groups. Patients receiving conscious sedation had a shorter anaesthetic time (mean (SD) 121 (28) min vs. 145 (41) min; p < 0.001) and recovery room time (110 (50) min vs. 155 (48) min; p = 0.001), lower requirement for inotropes (4.6% vs 81.8%; OR (95% CI) 0.1 (0.002–0.050); p < 0.001) and a lower incidence of malignant dysrhythmia (0% vs 11.4%; p = 0.020). Conscious sedation appears a feasible alternative to general anaesthesia for this procedure and is associated with a reduced requirement for inotropic support and improved efficiency.     

Microsurgical results with large vestibular schwannomas with preservation of facial and cochlear nerve function as the primary aim

Summary Objective. To evaluate our microsurgical results in dealing with vestibular schwannomas (VS) greater than or equal to 30 mm when preservation of cranial nerve function was considered more important than total tumour removal.Methods. Sixteen consecutive cases were operated on by the same neurosurgeon according to a prospective protocol using intraoperative neuro-monitoring (IONM) based on electromyographic and brain stem auditory evoked potential recordings. Facial nerve function was evaluated on the House-Brackmann Scale and cochlear nerve function on the Gardner-Robertson Scale. Someone not involved in the clinical management of our patients collected all data.Results. Fifteen patients showed facial nerve (FN) function of House-Brackmann grade (HBG) I or II at one year postoperatively and one kept the HBG IV she had preoperatively. Two patients of four maintained a cochlear nerve function of Gardner-Robertson grade (GRG) II. The tumour excision rates were: total, 68.7%; near total, 6.3%; subtotal, 18.7%, and partial, 6.3%. The average follow-up was 55 months (1–106). Three patients underwent radiotherapy later with growth stabilisation and no additional morbidity.Conclusion. When dealing with VS greater than or equal to 30 mm, microsurgery guided by IONM, with a rate of total or near-total tumour excision of about 75%, can retain socially acceptable facial nerve function (HBG I or II) in all cases and serviceable hearing (GRG I or II) in two cases out of four. Maintaining serviceable cranial nerve function should take precedence over total tumour excision.     

A prognostic index (bladder prognostic index) for bilharzial-related invasive bladder cancer

PURPOSE: Bladder cancer is still the most common solid tumor among adult males in Egypt because of the prevalence of bilharzial infestation, especially in the countryside. In this prospective study, we have recorded the prognostic factors for 180 patients with invasive bladder cancer for whom standard radical cystectomy had been performed to develop a prognostic index (bladder prognostic index) that defines high risk patients who are more vulnerable to disease relapse after surgery and who may benefit from additional therapy. PATIENTS AND METHODS: The study was performed between January 1997 and December 1999, in which 180 patients with histopathologically proved invasive bladder cancer associated with bilharziasis underwent radical cystectomy or anterior pelvic exenteration. After surgery, patients were regularly followed for a minimum of 2 years. RESULTS: Our patients included 141 males and 39 females. Squamous cell carcinoma was the most common type (53.3%), and most of the tumors were grade II (61.1%). A total of 173 patients had their tumors operable, while 7 were inoperable. We had 5 (2.8%) operative related mortalities. At 5 years postoperatively, free and overall survival rates for the whole group of patients were 31.44%+/-5.9% and 32.5%+/-6.8%, respectively. Tumor pathologic stage, grade, and nodal affection were the only significant factors with impact on survival (P=0.008, 0.051, and 0.004, respectively). These 3 prognostic indexes were used to design a model to predict an individual patient's risk factor for recurrence. Patients were then assigned to one of the 4 risk groups according to the score achieved in this prognostic index (0=low risk, 1=intermediate risk, and 2 or 3=higher risk). These 4 risk groups had distinctly different rates of disease-free survival, i.e., 91.7%, 53%, 13%, and 7% for low, intermediate, and higher risk groups, respectively. CONCLUSION: Although this prognostic index appears to be of a significant clinical relevance, it needs to be more validated on a larger number of patients, and it could be a surrogate variable for biologic factors responsible for the heterogeneity of bladder cancer.     

Methyl gallate isolated from Mangifera pajang kernel induces proliferation inhibition and apoptosis in MCF-7 breast cancer cells via oxidative stress

Objective:To determine the lead bioactive compound in kernel extract of Mangifera pajang and its anti-cancer activity against human breast cancer cell lines with positive estrogen receptor(MCF-7).Methods:The methanolic extract of dried powder kernel of Mangifera pajang was exposed to column chromatography for isolation.The structural elucidation of the isolated compound was characterized using infrared,nuclear magnetic resonance,mass spectrometry.Furthermore,cytotoxicity,morphological changes,flow cytometry and cell cycle arrest analyses were performed to examine the mechanism of anti-proliferation and apoptosis induced by methyl gallate against MCF-7.Results:One compound was isolated from the methanolic extract of Mangifera pajang kernel and identified as methyl gallate.The flow cytometric results demonstrated induction of apoptosis in MCF-7 cells by three concentrations of methyl gallate.The cell cycle arrest showed a significant(P<0.05)decrease in cell progression at G2/M phase of MCF-7 after treatment with 100μM of methyl gallate.The cell percentage of early and late apoptosis was significant at 10 and 100μM of methyl gallate.Also,methyl gallate treatment induced up-regulation of reactive oxygen species levels in MCF-7 cells with a reduction in superoxide dismutase levels.Conclusions:These findings indicate that isolated methyl gallate from Mangifera pajang kernel extracts induces growth inhibition and apoptosis in MCF-7 cells via up-regulating oxidative stress pathway.     

Giant cell tumour of talus--a case report

Giant cell tumour of the talus bone is rare and is usually seen in skeletally mature adults. Here a case of giant cell tumour of the talus in a skeletally immature boy of 15 years is reported. The patient presented with swelling and tenderness of the left ankle with an osteolytic lesion seen in the talus on x-ray. A trephine biopsy followed by left talar excision was done. Following the biopsy report the patient underwent arthotomy and joint clearance. There was no recurrence noted at six months follow-up.     

In vitro antifungal susceptibility testing of fungi in patients with onychomycosis

Onychomycosis is the most common nail disorder. To examine in vitro antifungal susceptibility of fungi among onychomycosis patients. The study included 68 patients with onychomycosis. Nail specimens were cultured on Sabouraud dextrose agar and Dermasel agar base‐media. Isolated fungi were subjected to antifungal susceptibility tests against terbinafine, itraconazole, fluconazole, and griseofulvin. Candida species (Candida spp.) were detected in 32.4% of the cases of candidal onychomycosis (n = 37), 23.5% of the cases of distal and lateral subungual onychomycosis (n = 17), and 21.4% of the cases of total dystrophic onychomycosis (n = 14). Candida spp. were sensitive to fluconazole in 73.5%, itraconazole in 58.8%, and terbinafine in 5.9% of the cases. Aspergillus spp. were sensitive to itraconazole in all cases, and terbinafine in 87.5% of cases. Penicillium spp. were sensitive to itraconazole and terbinafine in 88.9% and 77.8% of cases, respectively. Trichophyton spp. were sensitive to terbinafine and resistant to itraconazole. Microsporum spp. were sensitive to itraconazole and resistance to terbinafine. All isolated fungi were resistant to griseofulvin. An increasing proportion of Candida spp. was observed among patients with different clinical varieties of onychomycosis. Candida spp. were highly sensitive to fluconazole and a lesser extent to itraconazole.