Microbial isolates and HIV infection in couples attending fertility clinics in Sagamu, Nigeria.

This observational study was designed to determine the prevalence of HIV infection and the microbial isolates from the genital tracts of couples attending the fertility clinics of Olabisi Onabanjo University Teaching Hospital, Sagamu, Ogun State, Nigeria between January 2001 and December 2002. A total of 110 women and 49 of their male partners were recruited into the study. The majority of the patients were between 25 and 34 years (women: 71.8%; partners: 65.3%), though the men were significantly older than the women (p < 0.001). The overall prevalence of HIV infection in those who consented to screening was 8.2%, which was over twice the reported prevalence among the general population in Ogun State, Nigeria during the study period. Candida albicans (32.5%) and Staphylococcus aureus (27.5%) were the most frequently isolated microorganisms from the endocervix while Trichomonas vaginalis (37.9%) and Staphylococcus aureus (24.1%) were the most common microbes isolated from the posterior vaginal fornix. Of all the seminal qualities, only the volume showed a significant difference between the infected and non-infected samples (p < 0.004). This study suggests a higher prevalence of HIV infection among the infertile couples in our environment and it may be advisable to have them screened for HIV in the face of the present HIV situation in sub-Saharan Africa.     

The rise in caesarean birth rate in Sagamu, Nigeria: reflection of changes in obstetric practice.

A retrospective and comparative study of women delivered by caesarean section over two different 3-year periods was conducted at Olabisi Onabanjo University Teaching Hospital, Sagamu, Nigeria. The caesarean section rate (CSR) increased from 10.3% in 1989-1991 to 23.1% in 2000-2003. The most frequent indication in both periods was different: prolonged/obstructed labour (20.0%) in 1989-1991 and antepartum haemorrhage (14.9%) in 2000-2003. Malpresentation, antepartum haemorrhage and pre-eclampsia/eclampsia were responsible for 51.7% of the difference in the CSR recorded between both periods. The CSR rose from 13.3% to 25.0% while the instrumental vaginal delivery (IVD) rate decreased significantly by 11.4% among the nulliparous women between the periods. Increase in CSR can be attributed mainly to reduction in IVD rate and alteration in the management of labour complications and induction policy. Strategies to reduce the CSR should cut across all indications and focus on encouraging instrumental vaginal deliveries, especially among nulliparous women.     

Elective abdominal hysterectomy in Nigerian Jehovah's Witnesses.

In a retrospective study at a university hospital, the perioperative morbidity associated with elective total abdominal hysterectomy in 23 Jehovah's Witnesses was compared with that of 46 non-Witness controls. The mean operative blood loss was significantly less, the procedure was lengthier and the average postoperative hospital stay was longer in the study than in the control group. Febrile morbidity was insignificantly more frequent among the study group (OR: 2.05, CI: 0.61-6.88) and there was no significant difference between the overall morbidity experienced by patients in both groups (study: 43.5% versus control: 39.1%; P = 0.73). The perioperative morbidity associated with elective abdominal hysterectomy in patients unwilling to accept blood transfusion does not justify the denial of this important gynaecological surgery when indicated. Gynaecologists in poor resource settings should consciously aim at providing 'bloodless' care for all their patients undergoing abdominal hysterectomy as this may translate to reduced blood loss and decreased need for blood transfusion.     

Preclinical to Clinical Translation of CNS Transporter Occupancy of TD-9855, a Novel Norepinephrine and Serotonin Reuptake Inhibitor

Background:

Monoamine reuptake inhibitors exhibit unique clinical profiles that reflect distinct engagement of the central nervous system (CNS) transporters.

Methods:

We used a translational strategy, including rodent pharmacokinetic/pharmacodynamic modeling and positron emission tomography (PET) imaging in humans, to establish the transporter profile of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor.

Results:

TD-9855 was a potent inhibitor of norepinephrine (NE) and serotonin 5-HT uptake in vitro with an inhibitory selectivity of 4- to 10-fold for NE at human and rat transporters. TD-9855 engaged norepinephrine transporters (NET) and serotonin transporters (SERT) in rat spinal cord, with a plasma EC₅₀ of 11.7ng/mL and 50.8ng/mL, respectively, consistent with modest selectivity for NET in vivo.Accounting for species differences in protein binding, the projected human NET and SERT plasma EC₅₀ values were 5.5ng/mL and 23.9ng/mL, respectively. A single-dose, open-label PET study (4–20mg TD-9855, oral) was conducted in eight healthy males using the radiotracers [¹¹C]-3-amino-4- [2-[(di(methyl)amino)methyl]phenyl]sulfanylbenzonitrile for SERT and [¹¹C]-(S,S)-methylreboxetine for NET. The long pharmacokinetic half-life (30–40h) of TD-9855 allowed for sequential assessment of SERT and NET occupancy in the same subject. The plasma EC₅₀ for NET was estimated to be 1.21ng/mL, and at doses of greater than 4mg the projected steady-state NET occupancy is high (>75%). After a single oral dose of 20mg, SERT occupancy was 25 (±8)% at a plasma level of 6.35ng/mL.

Conclusions:

These data establish the CNS penetration and transporter profile of TD-9855 and inform the selection of potential doses for future clinical evaluation.