Hesham Khalil

Associations of Y-chromosome subdeletion gr/gr with the prevalence of Y-chromosome haplogroups in infertile patients

Microdeletions in azoospermia factor (AZF) region on distal Yq are associated with male infertility and spermatogenic failure due to intra-chromosomal homologous recombination between large nearly identical repeat amplicons and are found in ∼10% of azoospermic and severe oligozoospermic cases. Although AZFc is deleted in azoospermia or oligozoospermia, no definitive conclusion has been drawn for the role of partial AZFc deletions to spermatogenic failure. Therefore, this study is planned to investigate the role of gr/gr subdeletions in individuals with spermatogenic failure and to find its relationship with Y chromosome haplogroups (HGs) in infertile men from Indian population. It is a case-control study involving 236 azoospermic, 182 oligospermic and 240 healthy normozoospermic men. We found 18 gr/gr, 11 b1/b3 and 2 b2/b3 subdeletions in azoospermic patients and 12 gr/gr, 5 b1/b3 and 4 b2/b3 subdeletions in oligospermic patients. However, we also found seven gr/gr deletions in normozoospermic men. Seven patients each with spermatogenic arrest and oligospermia who carry gr/gr subdeletions have deleted DAZ3/DAZ4 genes. A total of 11 patients with sertoli cell-only syndrome (SCOS) and 5 oligospermic patients with gr/gr subdeletions also have DAZ1/DAZ2 genes deleted indicating that deletions of DAZ genes contributed differently to damage to spermatogenic process. L1 HG is found in patients showing b1/b3 subdeletions, whereas HG H1a2 and H1b were found in normozoospermic individuals with gr/gr subdeletions. Our results provide evidence of association between the occurrence of subdeletions and male infertility as well as the severity of the spermatogenic failure.

GSTP1 methylation and polymorphism increase the risk of breast cancer and the effects of diet and lifestyle in breast cancer patients

Glutathione S-transferases (GSTs) are an important group of isoenzymes that play an essential role in the detoxification of carcinogens. Polymorphism at exon 5 of the GST π family decreases the catalytic activity and affects the detoxification ability of the enzyme, GSTP1. GSTP1 promoter hypermethylation and loss of expression are frequently observed in various types of carcinoma. We hypothesized that somatic epigenetic modification in homozygous mutants increases the degree to which breast cancer risk is affected by lifestyle factors and dietary habits. The present study used tumor biopsies and blood samples from 215 breast cancer patients and 215 blood samples from healthy donors. GSTP1 polymorphism was studied using PCR-restriction fragment length polymorphism, methylation using methylation-specific PCR and loss of expression using immunohistochemistry and western blotting. No significant increase was observed in the breast cancer risk of individuals with the mutant (Val) allele [odds ratio (OR), 1.48; 95% confidence interval (CI), 0.97–2.26 for heterozygotes; OR, 1.42; 95% CI, 0.86–2.42 homozygous mutants]. GSTP1 promoter hypermethylation was detected in one-third of tumor biopsies (74/215) and was found to be associated with a loss of expression. Genotype and tumor methylation associations were not observed. Estrogen (ER) and progesterone (PR) receptor-positive tumors had a higher methylation frequency. GSTP1 polymorphism was not associated with increased promoter hypermethylation. The results suggest that GSTP1 methylation is a major event in breast carcinogenesis and may act as a tumor-specific biomarker.

A SRY-HMG box frame shift mutation inherited from a mosaic father with a mild form of testicular dysgenesis syndrome in Turner syndrome patient

BackgroundSex determining factor (SRY) located on the short arm of the Y chromosome, plays an important role in initiating male sex determination, resulting in development of testicular tissue. Presence of the SRY gene in females results in XY sex reversal and increased risk of gonadal germ cell tumours if the karyotype also includes the so-called GonadoBlastoma on the Y chromosome (GBY) region. The majority of mutations within the SRY gene are de novo affecting only a single individual in the family. The mutations within the high-mobility group (HMG) region have the potential to affect its DNA binding activity.Case PresentationWe performed G- and R-banding cytogenetic analysis of the patient and her family members including her father. We also performed molecular genetic analysis of SRY gene. Cytogenetic analysis in the patient (Turner Syndrome) revealed the mosaic karyotype as 45, X/46, XY (79%/21% respectively) while her father (milder features with testicular dysgenesis syndrome) has a normal male karyotype (46, XY). Using molecular approach, we screened the patient and her father for mutations in the SRY gene. Both patient and her father showed the same deletion of cytosine within HMG box resulting in frame shift mutation (L94fsX180), the father in a mosaic pattern. Histological examination of the gonads from the patient revealed the presence of gonadoblastoma formation, while the father presented with oligoasthenozoospermia and a testicular seminoma. The frameshift mutation at this codon is novel, and may result in a mutated SRY protein.ConclusionOur results suggest that lack of a second sex chromosome in majority cells of the patient may have triggered the short stature and primary infertility, and the mutated SRY protein may be associated with the development of gonadoblastoma. It is of importance to note that mosaic patients without a SRY mutation also have a risk for malignant germ cell tumors.

Surgical templates for dental implant positioning; current knowledge and clinical perspectives.

Dental implants have been used in a variety of different forms for many years. Since the mid-20 th century, there has been an increase in interest in the implant process for the replacement of missing teeth. Branemark was one of the initial pioneers who applied scientifically based research techniques to develop an endosseous implant that forms an immobile connection with bone. The need for a dental implant to completely address multiple physical and biological factors imposes tremendous constraints on the surgical and handling protocol. Metallic dental implants have been successfully used for decades, but they have serious shortcomings related to their bony union and the fact that their mechanical properties do not match those of bone. However, anatomic limitation and restorative demands encourage the surgeon to gain precision in planning and surgical positioning of dental implants. Ideal placement of the implant facilitates the establishment of favorable forces on the implants and the prosthetic component as well as ensures an aesthetic outcome. Therefore, it is advisable to establish a logical continuity between the planned restoration and the surgical phases, it is essential to use a transfer device that for sure increases the predictability of success. The surgical guide template is fabricated by a dental technician after the presurgical restorative appointments that primarily include determination of occlusal scheme and implant angulations. Here, authors genuinely attempted to review the evolution and clinical applicability of surgical templates used in the placement of dental implants.

A basic review on the inferior alveolar nerve block techniques

The inferior alveolar nerve block is the most common injection technique used in dentistry and many modifications of the conventional nerve block have been recently described in the literature. Selecting the best technique by the dentist or surgeon depends on many factors including the success rate and complications related to the selected technique. Dentists should be aware of the available current modifications of the inferior alveolar nerve block techniques in order to effectively choose between these modifications. Some operators may encounter difficulty in identifying the anatomical landmarks which are useful in applying the inferior alveolar nerve block and rely instead on assumptions as to where the needle should be positioned. Such assumptions can lead to failure and the failure rate of inferior alveolar nerve block has been reported to be 20-25% which is considered very high. In this basic review, the anatomical details of the inferior alveolar nerve will be given together with a description of its both conventional and modified blocking techniques; in addition, an overview of the complications which may result from the application of this important technique will be mentioned.

Dental extraction in patients on warfarin treatment

Background Warfarin is one of the most common oral anticoagulants used to prevent thromboembolic episodes. The benefits of discontinuation of this drug before simple surgical procedures are not clear and this approach could be associated with complications. The aim of this study was to evaluate the risk of bleeding in a series of 35 patients (in cases where the international normalized ratio [INR] is less than 4) following simple tooth extraction without modification of the warfarin dose given to patients. Methods Thirty-five patients taking warfarin who had been referred to the Oral and Maxillofacial Department, College of Dentistry, King Saud University, for dental extractions were included in the study. Exclusion criteria included patients with an INR of ≥4 or with a history of liver disease or coagulopathies. No alteration was made in warfarin dose, and the CoaguChek System was used to identify the INR on the same day of dental extraction. Bleeding from the extraction site was evaluated and recorded immediately after extraction until the second day. Results A total of 35 patients (16 women and 19 men) aged between 38 and 57 years (mean =48.7) were included in the present study. All patients underwent simple one-tooth extraction while undergoing warfarin treatment. Oozing, considered mild bleeding and which did not need intervention was seen in 88.6% of patients. Moderate bleeding occurred in 11.4% of all cases. The INR of the patients ranged from 2.00 to 3.50, with 77.2% of patients having INR between 2.0 and 2.5 on the day of extraction. No severe bleeding which needed hospital management was encountered after any of the extractions. The patients who suffered moderate bleeding were returned to the clinic where they received local treatment measures to control bleeding. Moderate bleeding occurred only in four patients, where three had INR between 3.1 and 3.5, and one with INR less than 3. Conclusion In the present study, we have shown that simple tooth extraction in patients on warfarin treatment can be performed safely without high risk of bleeding, providing that the INR is equal or less than 3.5 on the day of extraction. A close follow-up and monitoring of patients taking warfarin is mandatory after dental extraction.

Reasons for and patterns relating to the extraction of permanent teeth in a subset of the Saudi population.

Background The purpose of this study was to investigate the reasons for and patterns of extraction of permanent teeth in a subset of the Saudi population. Methods During a 3-month period, dentists were asked to record, using a specially designed survey form, the reasons for every extraction of a permanent tooth. The reasons for tooth extraction were assigned to different causes, ie, dental caries, periodontal disease, eruption problems, trauma, orthodontics, failed root canal treatment, and others. The data requested for each extraction were: patient age, gender, nationality, and type of tooth removed and the reason for its extraction. Results The highest percentage of extractions was observed in young females aged 10–30 years. Presence of caries was observed to be the main reason for extraction (50.2%) followed by orthodontic problems (18.2%), eruption problems (17.5%), and periodontal problems (8.2%). The most frequently extracted posterior teeth were the third mandibular molar (19.4%), the third maxillary molar (16.4%), the first maxillary premolar (13.2%), and the first mandibular molar (10.9%). Conclusion Dental caries was found to be the most common reason for extraction of teeth. Molar teeth were found to be the most frequently extracted, with an increased number of extracted first premolars as a result of orthodontic treatment. The highest percentage of extractions was observed in young females aged 10–30 years.

Transpalatal distraction osteogenesis prior to alveolar bone grafting in cleft lip and palate patients

Alveolar bone grafting is a standard method for treating alveolar cleft. To ensure the best outcome, improving the arch form as well as soft tissue quality in the area around the cleft is recommended. In this study, 11 patients who presented with alveolar cleft and collapsed maxillary arch were treated in the following sequence: transpalatal distraction osteogenesis followed by soft tissue surgery in some cases and by cancellous bone graft. In all cases, transpalatal distraction osteogenesis successfully corrected the transverse maxillary deficiency. One case showed a complete loss of the bone graft. Other minor complications were reported but they did not affect the final outcome.

Articaine (4%) Buccal Infiltration versus Lidocaine (2%) Inferior AlveolarNerve Block for Mandibular Teeth Extraction in Patients on WarfarinTreatment

Background: Although lidocaine inferior alveolar nerve block is a common dental injection in case of managing mandibular teeth, it may not be the first choice in specific situations. Patients on warfarin therapy are at high risk of bleeding during dental procedures. In this study we aimed to investigate and compare the efficacy of articaine buccal infiltration in mandibular teeth extraction with lidocaine inferior alveolar nerve block for extraction of mandibular teeth in patients on warfarin treatment. Methods: Patients included in the present study were on warfarin treatment and referred for simple dental extraction. Patients were divided randomly in two groups, one group received standard inferior alveolar nerve block (1.8 ml of 2% lidocaine with 1:80,000 adrenaline) and the second group received buccal infiltration supported with lingual infiltration using 4% articaine and 1:100,000 adrenaline. Data was analyzed by descriptive analysis using SPSS program V.17. A Mann-Whitney U test to compare the results and p value of less than 0.05 was considered significant. Results: A total of 23 adult patients (10 women and 13 men) aged 40 to 57 years (mean=48.9) were recruited into the study with 6 excluded as they needed a second local anesthetic cartridge to obtain profound anesthesia. The success rate of inferior alveolar nerve block using lidocaine was 81.8% while the success rate for articaine buccal infiltration in obtaining good profound pulpal anesthesia was 66.6%. Both surgeons and patients were satisfied with anesthesia using both drugs. Conclusion: Buccal infiltration of 4% Articaine for mandibular teeth can have a high success rate using one local anesthetic cartridge, and is considered a good alternative option for nerve block in patients on warfarin treatment to avoid complication related to the nerve block.

Willingness of Saudi dental professionals to treat Hepatitis B virus-infected patients

BACKGROUND Hepatitis B virus (HBV) is considered the most important cross-infection hazard in developing countries. Patients infected with hepatitis virus could encounter difficulties in obtaining dental care. The aim of this study was to investigate the willingness of Saudi dental professionals to treat hepatitis B virus infected patients. MATERIALS AND METHODS This cross-sectional survey was carried out by distributing 300 questionnaires to Saudi dentists working in 40 government and private dental centers in Riyadh, Saudi Arabia. The questionnaire included questions related to age, sex, vaccination against HBV, screening for HBV antibody levels, willingness to treat hepatitis B infected patients, and the reasons behind any refusal. A t-test was used to compare the results and a P < 0.05 was considered significant. RESULTS Of the 300 distributed questionnaires, 274 were collected giving a response rate of 91%. The respondents were 212 males (77.4%) and 62 (22.6%) females. Only 10.2% of the Saudi dentists were willing to treat HB infected patients. The other dentists (89.8%) were unwilling to provide dental care for HB infected patients. Although 94.5% of the surveyed dentists were vaccinated against HBV, the main reason behind the refusal to treat HB infected patients (92.3%) was the risk of cross infection. CONCLUSION High percentages of Saudi dentists are unwilling to treat HBV-infected patients due to their apprehension about risk of cross infection. Many of the Saudi dentists do not screen for HBV antibody levels. All vaccinated dentists should carefully monitor their antibody levels to evaluate the need for booster doses. There is a need for educational programs to change the attitude of dentists toward treating HBV-infected patients. The strict adoption of cross infection preventive protocols by dentists will reduce the risk of transmitting infectious diseases in dental clinics as identification of blood-borne infections is not always possible.