Novel biallelic loss-of-function mutations in / 亚洲男科学杂志(英文版)

Multiple morphological abnormalities of the sperm flagella (MMAF) is a specific type of asthenoteratozoospermia, presenting with multiple morphological anomalies in spermatozoa, such as absent, bent, coiled, short, or irregular caliber flagella. Previous genetic studies revealed pathogenic mutations in genes encoding cilia and flagella-associated proteins (CFAPs; e.g., CFAP43, CFAP44, CFAP65, CFAP69, CFAP70, and CFAP251) responsible for the MMAF phenotype in infertile men from different ethnic groups. However, none of them have been identified in infertile Pakistani males with MMAF. In the current study, two Pakistani families with MMAF patients were recruited. Whole-exome sequencing (WES) of patients and their parents was performed. WES analysis reflected novel biallelic loss-of-function mutations in CFAP43 in both families (Family 1: ENST00000357060.3, p.Arg300Lysfs*22 and p.Thr526Serfs*43 in a compound heterozygous state; Family 2: ENST00000357060.3, p.Thr526Serfs*43 in a homozygous state). Sanger sequencing further confirmed that these mutations were segregated recessively in the families with the MMAF phenotype. Semiquantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was carried out to detect the effect of the mutation on mRNA of the affected gene. Previous research demonstrated that biallelic loss-of-function mutations in CFAP43 accounted for the majority of all CFAP43-mutant MMAF patients. To the best of our knowledge, this is the first study to report CFAP43 biallelic loss-of-function mutations in a Pakistani population with the MMAF phenotype. This study will help researchers and clinicians to understand the genetic etiology of MMAF better.

Clinical Evaluation of Pit and Fissure Sealants Placed by Undergraduate Dental Students in 5-15 Years-old Children in Iraq

Abstract Objective: To clinically evaluate the retention and marginal discoloration of pit and fissure sealants applied to primary and permanent teeth. Material and Methods: The study population encompassed of 5-15 years-old children. After consenting, a light-curing sealant was applied to etched pits and fissures of occlusal surfaces of selected sound teeth. The retention rate and marginal discoloration were assessed, 3 months after application of the sealants based on the criteria proposed by Simonsen's criteria (total retention: score 0, partial loss: score 1, and total loss: score 2). Each tooth was considered as an independent sample during analysis. Results: The achieved sample size was 43 children aged 5-15 years (mean age=10.0 years). Therefore, data of 100 teeth from 43 children were used for the final analysis. The percentage of completely retained sealants (59%) was higher than the percentage of partially retained sealants (23%) and completely missing sealants (18%) after 3 months follow up. Out of 100 sealed teeth, 60% were either had marginal discoloration or completely missing. Using the Mann-Whitney test, there was a statistically significant difference (p<0.05) between primary and permanent teeth in terms of retention. However, there was no statistical difference (p>0.05) between upper and lower teeth in terms of retention. Conclusion: The success rate of fissure sealants after 3 months follow-up was satisfactory.

Effect of previous exposure to HBV on liver histology and treatment response in CHC patients

To analyze the influence of previous exposure to HBV on liver histology and treatment outcomes in chronic hepatitis C [CHC] patients. Case control study. Rawalian Liver Clinic, Department of Medicine, Holy Family Hospital, Rawalpindi, from January 2011 to December 2012. Medical records of CHC patients attending the Rawalian Liver Clinic were retrospectively analyzed. Virological and treatment responses along with histological changes were compared between cases [anti-HBc positive] and controls [anti-HBc negative]. Significance was determined through chi-square test at p < 0.05. Among the 592 CHC patients, 254 [42.9%] had serological evidence of a positive anti-HBc [cases] and 338 [57.1%], patients had negative anti-HBc [controls]. No significant difference was found between ETR, SVR and treatment responses [n=220] between the two groups. Out of 65 patients whose liver biopsy data was available, cases were more likely to respond in the absence of fibrosis [63.2%, [n=24] vs. 36.8%, [n=14], p=0.001]. The controls responded more in the presence of fibrosis [100% [n=9] vs. 0, p=0.001]. There was no significant effect of anti-HBc positivity on grades of inflammation and consequent treatment response [p=0.14]. There are a significant number of CHC patients with markers of previous HBV infection in Pakistani population. Previous HBV [anti-HBc positive] does not seem to have an adverse effect on liver histology and treatment responses in HBV infection

A review of ethics in developing country in perspective of dental research.

ABSTRACT: The objectives of this review were to examine the ethical issues in research in developing country and perspective of dental research. In this review, we performed the systematic literature search, screening process through the web in existing published and unpublished articles and reports that related to our topics between1990 to 2013. In the past few decades, the research and discoveries in the discipline of dentistry have increased dramatically. Recently many dental Institutes in developing country is constantly looking for opportunities to borrow, enhance, and integrate knowledge from biomedical and technological research by using modern technology. The retrieved information in this review reflect that to make any research involving human subjects ethically acceptable, a number of key features have to be considered by the researchers. Those who conduct oral health research are compelled by regulations and convention to follow established ethical standards to protect human rights. Bioethics and in ethical review of research in developing countries reveals many major gaps and have seen that there are indeed many ethical issues to be considered to clinical trials taking place in developing countries. Professional societies have a major influence in shaping the moral tone and ethical climate for research through the adoption of standards, the development of educational programs designed to reinforce those standards. Research ethics committees or institutional ethical review committees is to ensure that studies involving human research participants are designed to conform the relevant ethical standards and that the rights and welfare of participants are protected. Research ethics committees should not function under the influence of others and should ensures the favorable balance of potential benefits and risks. In developing country it is necessary to strengthen local capacity and manpower by developing innovative training models for ethics that are cost-effective and sustainable. The actions required to move ahead in this field include strengthening bioethics capacity, linking health research to community needs in a transparent and participatory process and increasing communication between scientists and ethicists in industrialized and developing countries

Safety of non-anaesthesiologist-administered propofol sedation in ERCP

Propofol is increasingly being used for sedation purposes during endoscopic retrograde cholangiopancreatography [ERCP]. This study aimed to evaluate the safety of nonanaesthesiologist administration of propofol [NAAP] during therapeutic ERCP. Patients, who underwent ERCP at Centre for Liver and Digestive Diseases, Holy Family Hospital, Rawalpindi, were included in the study. Propofol sedation was administered by a physician who was a non-anaesthesiologist certified in basic and advanced cardiac life support. The total study duration was 6 months. The primary outcome variable was the frequency of any sedation-related complication. A total of 156 patients [41% males and 59% females] were enrolled in the study. The mean propofol dose used during the procedure was 201 +/- 132 mg. The mean propofol dose, when adjusted to weight and duration of procedure, was 0.05 +/- 0.04 mg kg[-1] min[-1]. According to the American Society of Anesthesiologists [ASA] classification. 136 [87%] patients were placed in ASA class I and II and 20 [13%] patients were of ASA class III. Only two patients developed sedation-related complication: one minor requiring bag-mask ventilation and other major requiring mechanical ventilation via endotracheal intubation. Both were managed by the trained non-anaesthesiologist and gastroenterologist at the pIace of procedure. No patients required cardiopulmonary resuscitation and admission to the intensive care unit. There were no sedation-related deaths. NAAP sedation can be considered safe for low-risk patients [ASA class I and II] undergoing ERCP. The presence of a trained anaesthetist is advisable in high-risk patients [ASA class III and higher] with significant co-morbidities

Incremental diagnostic value and impact on patient management of somatostatin receptor scintigraphy with indium-111-pentetreotide in gastroenteropancreatic neuroendocrine tumors

To evaluate the efficacy of somatostatin analog scintigraphy with indium-111-pentetreotide and its overall impact on management in patients with gastroenteropancreatic neuroendocrine tumors [GEP-NET]. Twenty-two consecutive patients with a proven or clinically suspected GEP-NET with or without proven metastases were imaged at 24 and 48 h after injection of [111] In-pentetreotide. The scintigraphic findings were compared with results from conventional imaging methods. The final diagnosis was based on histopathological and surgical findings and complementary radiology. Somatostatin receptor-positive lesions were found in 20 of the patients, whereas conventional methods were positive in 18 patients. Additionally, 13 new tumor sites were discovered by somatostatin receptor scintigraphy in 5 patients [liver: 6; chest: 2; bone: 1; abdomen: 4]. The surgical therapeutic strategy was changed in 7 patients [32%]. Our data reinforced that scintigraphy with [111]In-pentetreotide represents the imaging modality of choice in the initial evaluation of GEP-NET. It is highly accurate and can identify clinically unsuspected lesions and optimize the overall staging. It also guides optimal therapy choice and most importantly identifies patients with inoperable or metastatic disease who might be candidates for high-dose targeted therapy

Emphysematous Pyelonephritis

Urinary tract infection is very common and in most cases is self limiting even without treatment. However, in some cases, the infection may progress and leads to serious complication requiring admission and treatment. Emphysematous pyelonephritis is a rare but serious complication of urinary tract infection. The symptoms are similar to those seen in pyelonephritis and without radiological imaging; the diagnosis can be missed with serious consequence. In severe cases, nephrectomy may be indicated. We report a case of emphysematous pyelonephritis in a previously well obese 28 year old lady who was successfully managed with intravenous antibiotic. Her underlying risk factor was undiagnosed diabetes mellitus.

Strangulation injuries of the penis

Objectives: To report the series of cases of penile strangulation injuries which were managed in our setting

Patients and Methods: 5 cases of penile strangulation were managed in our department during last five years. Three patients were admitted through emergency and 2 patients were admitted through out patient department. Complete history was taken and physical examination done. Type of strangulating agent and duration of strangulation were documented. Treatment was individualized for every patient

Results: The age range of the patients was 17 to 58 years. Duration of strangulating agent was from 24 hours to 6 months. In 1 patient, who had strangulation due to string, constricting agent was divided and recovery was uneventful. Two cases having strangulation due to wheel bearing, one needed debridement of the glans and later on skin grafting of penile shaft, results were satisfactory. Other case, whose penile shaft wound was debrided, was planned for grafting but he left against medical advice. Two patients, who had amputation of glans showed satisfactory outcome after revision of stumps

Conclusion: Penile strangulation injuries are very serious leading to even loss of organ. These should be recognized early and prompt removal of strangulation agent is necessary to prevent serious complications

Minimally invasive radionuclide-guided parathyroidectomy using [99m] Tc-Sestamibi in patients with primary hyperparathyroidism: a single-instituion experience

To evaluate the efficacy and usefulness of [99m]Tc- sestambi sccintigraphy and gamma probe localization of parathyroid glands in patients with primary hyperparathyroidism and establish radio-guided minimally invasive parathyroidectomy at Hussain Makki Al Jumma Center for Specialized Surgery, Kuwait. Twelve patients with primary hyperparathyroidism [mean age: 48 +/- 14 years; median age: 46 years; age range-29-68 years] were evaluated. The diagnosis of hyperparathyroidism was established by elevated serum calcium and parathyroid hormone levels. All patients had a well-defined parathyroid lesion on previous standard [99m]Tc-sestambi scintigraphy with or without ultrasound study. All had a normal thyroid gland, no history of familial hyperparathyroidism or multiple endocrine neoplasia nor any history of previous neck irradiation. On the day of surgery, patients were injected with 740 MBq [20mCi] of [99m]Tc-sestamibi followed by a half-hour-delayed single standard pinhole view of the neck. A skin marker was placed on the basis of maximum count intensity during gamma probe localization. Patients were then sent for radio-guided minimally invasive parathyroidectomy. The preoperative localization of the affected gland was successful in all cases using a gamma probe and [99m]Tc-sestamibi scintigraphy. The pathological parathyroid tissue was localized and successfully removed with the gamma probe. The histopathological diagnosis was parathyroid adenoma in 11 cases and hyperplasia in the remaining one. All patients remained disease and symptom free at 12-month follow-up. Our initial experience with intraoperative use of a gamma probe to carry out minimally invasive parathyroidectomy was a useful, easy and safe procedure for treating patients with primary hyperparathyroidism

Prediction of cardiac events in patients having left bundle-branch block with/without chest pain using dipyridamole technetium-99m-sestamibi myocardial perfusion imaging

To determine the prognostic value of myocardial perfusion scintigraphy with dipyridamole stress in patients with preexisting left bundle-branch block [LBBB] with or without chest pain. Seventy-six patients, mean age 53 +/- 10 years, with preexisting LBBB underwent technetium-99m-sestamibi perfusion imaging with dipyridamole infusion protocol [0.56 mg/kg]. Stress and rest single photon emission computed tomography [SPECT] images were interpreted by consensus of 2 experienced nuclear medicine physicians and classified as low-risk scans [normal myocardial perfusion scan, small reversible/small fixed defect] and high-risk scans [large, severe, fixed or reversible defect and dilated left ventricle cavity]. The patients were followed up for 24 +/- 8 months and occurrences of hard cardiac events [infarction or cardiac death] were noted. Of the 76 patients, 52 [68%] had low-risk scans and the remaining 24 [32%] had high-risk scans. In the low-risk group, 1 [1.9%] cardiac death and 2 [3.8%] cases of nonfatal myocardial infarction occurred, while in the high-risk group, 5 [20.8%] suffered cardiac death, and 3 [12.5%] nonfatal myocardial infarction. Overall survival rate was 98.1% in the low-risk group compared with 79.2% in the high-risk group with a significant difference of p = 0.034. Negative predictive value of normal myocardial perfusion scintigraphy for the occurrence of death was 100%. No significant difference in survival rate among patients with or without chest pain [p = 0.31] was observed. Myocardial perfusion imaging with dipyridamole provided important prognostic information in patients with LBBB; it was useful in stratifying the patients according to cardiovascular morbidity and mortality, and would thus allow the clinician to provide early treatment especially in the high-risk category

Depression in primary care: Clinical epidemiology and clinical decision analysis an analytical review

A clinical decision analysis [CDA] is a mathematical tool designed to facilitate complex clinical decisions in which many variables should be considered simultaneously. CDA is a feasible tool for multifaceted problem of management of depression in primary health care. It provides a systematic frame work for organizing all data relevant to the decision on recognition and management of depression. Clinical epidemiological perspective is used for assessing the validity of screening instrument. A decision matrix based on reported probabilities is also constructed. Chance nodes and decisions pertinent to co-morbidities, illness severity and treatment options for depression are also presented

Study of lipoprotein profile in myocardial infarction

Serum cholesterol and lipoprotein levels were measured in thirty patients of myocardial infarction [23 males and 7 females] admitted to a coronary care unit Mayo Hospital Lahore. The patients were divided into two main groups, which were further classified in various subgroups according to age. The results were compared with eighteen healthy males and five female subjects. The serum cholesterol was higher in all age groups in patients than in normal controls. The HDL cholesterol concentration was lower in patients with different age groups of either sex when compared with healthy controls. The inverse relationship of HDL cholesterol in patients with myocardial infarction was evident