Trinucleotide (CAG) repeat polymorphisms in the androgen receptor gene: molecular markers of risk for male infertility.

OBJECTIVE: To determine whether changes in the polymorphic trinucleotide (CAG) tract of the androgen receptor gene are associated with spermatogenic defects in patients with male infertility. DESIGN: Case-control study of two ethnic groups. SETTING: University referral centers for male infertility at Baylor College of Medicine, Houston, Texas, and National University Hospital, Singapore. PARTICIPANT(S): Two hundred and fifteen patients with male infertility and depressed spermatogenesis and 142 fertile controls. MAIN OUTCOME MEASURE(S): Size of androgen receptor CAG alleles according to fluorescent-labeled polymerase chain reaction and automated analysis using Genescan software (PE Biosystems Asia, Singapore), and statistical examination of its relation to clinical variables. RESULT(S): In U.S. patients, the mean androgen receptor CAG length was significantly longer in infertile patients than in fertile controls (21.95 +/- 0.31 vs. 20.72 +/- 0.52). Logistic regression showed that each unit increase in CAG length was associated with a 20% increase in the odds of being azoospermic. The odds ratio for azoospermia was sevenfold higher for patients with > or =26 CAG repeats than in those with <26 CAG repeats. Although mean CAG length in Singapore patients was longer than in the U.S. samples, long androgen receptor CAG alleles were significantly related to male infertility in both populations. CONCLUSION(S): Long (> or =26) androgen receptor CAG alleles, which are found in up to 25% of azoospermic men, are associated with male infertility and defective spermatogenesis. Conception in these men is possible with assisted reproductive technologies, as many have spermatozoa in their testes.

Problems and pitfalls in the management of Hirschsprung's disease.

A study of 126 patients with histologically proven Hirschsprung's disease revealed various problems associated with the surgical management of these cases. Complications such as prolapse, stricture, and cuff abscess were noted in patients undergoing endorectal pull-through (ERPT). These complications were not always obvious, and in some cases, the diagnosis became apparent only several years after definitive surgery. Specific technical aspects of the procedure probably play an important role in the pathogenesis of these problems. Ultrashort-segment Hirschsprung's disease remains a problem in treatment. Rectal myectomy gives good results in some cases and unsatisfactory results in others.

Experience in the surgical management of Hirschsprung's disease.

The clinical presentation, surgical treatment and results in a group of 126 patients with histologically proven Hirschsprung's disease are presented. This study has enabled the authors to identify various problems and complications associated with the management of this condition. The typical clinical picture in the neonate has been observed in only 45.2% of our cases. In the long segment Hirschsprung's, especially those presenting with bowel perforation, the precise localisation of the aganglionic segment has been difficult. The standard surgical procedure in our department has been the mucosal-stripping endorectal pull-through operation. The problems of prolapse, stricture and cuff abscess associated with this procedure are, related to specific technical aspects of the operation which we believe have not been emphasised previously. Our current experience with this type of procedure has enabled us to carry out definitive surgery in early infancy without preliminary colostomy. The results justify our confidence that this approach to the surgical management of neonatal Hirschsprung's disease will become the standard procedure in our practice. An unusual feature has been the relatively common occurrence of the short segment type of Hirschsprung's disease--30.2% with rectal aganglionosis and 7.1% with ultrashort segment disease. This group has posed a dilemma as to the selection of the most appropriate surgical procedure. Rectal myectomy, which was the operation of choice, has given excellent results in some cases and yet in other cases it has been unsatisfactory, leading to the development of very gross megacolon.

Genetics of male infertility: role of androgen receptor mutations and Y-microdeletions.

INTRODUCTION: Although infertility affects about 5% of the male population, its cause in most cases is uncertain. Normal spermatogenesis depends on a sequential cascade of genetic events triggered by factors encoded by the sex chromosomes. To determine the contribution of genetic aberrations to male infertility, the X-linked androgen receptor gene and the Y-chromosome were examined for mutations in a large cohort of infertile men. METHODS: Screening of the androgen receptor (AR) gene for single-stranded conformation polymorphisms, confirmation by DNA sequencing, structure-function studies with androgen-responsive reporter genes and chimeric-protein constructs were performed. Y-chromosome microdeletions screening was done with multiplex polymerase chain reaction (PCR) analyses. RESULTS: Genetic screening of over 400 patients and controls showed that defects in the androgen receptor gene lead to the production of dysfunctional receptor protein in 15% of males with abnormally low sperm production. The dozens of mutations and polymorphisms uncovered were associated with reduced intrinsic androgen receptor activity and involve principally two regions of the androgen receptor. Gene-transfer experiments implicated defective intermolecular protein-protein interactions with coactivator molecules as the cause of reduced receptor function. Submicroscopic deletions of the Y-chromosome were also been detected in about 6% of patients with severely reduced spermatogenesis. The deleted segments encoded RNA-binding proteins of unknown function and are not linked to defects in the androgen receptor. CONCLUSIONS: Mutations and polymorphisms of the AR, and Y-microdeletions cause defective sperm production and male infertility in about 20% of subfertile men. These traits can be transmitted to progeny, and counselling can be offered to affected families. Clarification of the molecular mechanisms of pathogenesis has led to rational hormonal therapy.

Endodontic interappointment emergencies in a Singapore private practice setting: a retrospective study of incidence and cause-related factors.

One thousand and sixteen consecutive records of patients treated by the author for endodontic treatment was surveyed for the incidence of endodontic interappointment emergencies (EIE) and the major factors contributing to it. The overall incidence of EIE was 3.15% and unrelated to the patients' sex or tooth location. Caucasians were more likely to experience flare-ups than Chinese (p < 0.01). Patients < 20 years and > 60 years were less likely to experience EIE (p < 0.05). EIE was significantly higher in necrotic teeth than in vital teeth (p < 0.01). A clinical diagnosis of necrotic pulp with acute apical abcess (NP/AAA) increased the incidence of flare-ups significantly (p < 0.05). Retreatment cases also had a higher incidence of EIE and this was statistically significant (p < 0.01). The possibility of EIE was the highest after the first visit (p < 0.01) and this was reduced significantly with subsequent visits.

Audit on cardiovascular disease preventive care in general practice.

INTRODUCTION: Cardiovascular disease is a major cause of morbidity and mortality. Primary care doctors as general practitioners (GPs) play a central role in prevention, as they are in contact with a large number of patients in the community through provision of first contact, comprehensive and continuing care. This study aims to assess the adequacy of cardiovascular disease preventive care in general practice through a medical audit. METHODS: Nine GPs in Malaysia did a retrospective audit on the records of patients, aged 45 years and above, who attended the clinics in June 2005. The adequacy of cardiovascular disease preventive care was assessed using agreed criteria and standards. RESULTS: Standards achieved included blood pressure recording (92.4 percent), blood sugar screening (72.7 percent) and attaining the latest blood pressure of equal or less than 140/90 mmHg in hypertensive patients (71.3 percent). Achieved standards ranged from 11.1 percent to 66.7 percent in the maintenance of hypertension and diabetic registries, recording of smoking status, height and weight, screening of lipid profile and attaining target blood sugar levels in diabetics. CONCLUSIONS: In the nine general practice clinics audited, targets were achieved in three out of ten indicators of cardiovascular preventive care. There were vast differences among individual clinics.

Removal of a laryngeal foreign body using high frequency jet ventilation.

Aspiration of a foreign body into the respiratory tract is a common and serious accident in childhood. Laryngotracheal foreign bodies, although less common than bronchial foreign bodies, are potentially more dangerous. Removal is commonly achieved using a rigid ventilating bronchoscope. We report a 16-month-old boy who had an open safety pin impacted in his larynx. This was removed through a tracheostomy, using high frequency jet ventilation to maintain gaseous exchange. We believe that this is the first case in which this method of removal has been reported.