Drosophila modifier screens to identify novel neuropsychiatric drugs including aminergic agents for the possible treatment of Parkinson's disease and depression.

Small molecules that increase the presynaptic function of aminergic cells may provide neuroprotection in Parkinson's disease (PD) as well as treatments for attention deficit hyperactivity disorder (ADHD) and depression. Model genetic organisms such as Drosophila melanogaster may enhance the detection of new drugs via modifier or 'enhancer/suppressor' screens, but this technique has not been applied to processes relevant to psychiatry. To identify new aminergic drugs in vivo, we used a mutation in the Drosophila vesicular monoamine transporter (dVMAT) as a sensitized genetic background and performed a suppressor screen. We fed dVMAT mutant larvae ∼ 1000 known drugs and quantitated rescue (suppression) of an amine-dependent locomotor deficit in the larva. To determine which drugs might specifically potentiate neurotransmitter release, we performed an additional secondary screen for drugs that require presynaptic amine storage to rescue larval locomotion. Using additional larval locomotion and adult fertility assays, we validated that at least one compound previously used clinically as an antineoplastic agent potentiates the presynaptic function of aminergic circuits. We suggest that structurally similar agents might be used to development treatments for PD, depression and ADHD, and that modifier screens in Drosophila provide a new strategy to screen for neuropsychiatric drugs. More generally, our findings demonstrate the power of physiologically based screens for identifying bioactive agents for select neurotransmitter systems.

Effect of Spinal Anaesthesia on Hearing Threshold

Background: Hearing loss following spinal anaesthesia is a known yet uncommonly reported complication. This study was aimed at determining the incidence and type of hearing loss (HL) following spinal anaesthesia (SA) and the relationship with the size of spinal needle. Methods: A prospective study of patients scheduled for spinal anaesthesia for surgery at the Operating room and Otorhinolaryngology department in a tertiary centre was undertaken. The audiometry was done and the pre- and post - anaesthesia results were compared.Results: Ninety - four ears of 47 patients; 16 males and 31 females; age range between 21 and 63 years (mean + SD= 41+5) were included. The duration of anaesthesia was between 90 and 150 minutes (mean + SD= 116+9). HL was seen in 9 ears of 7 patients (15) and tinnitus in 14 ears. The preoperative and postoperative BC PTA were 10 - 45dB (mean + SD= 26+ 5) and 25 - 65dB (mean + SD=38+5) respectively; (P= 0.02) while the preoperative and postoperative AC PTA in the early frequency range (0-100Hz) were between 5 - 45dB (mean + SD= 20+ 5) and 25 - 50dB (mean + SD=25+7) respectively; (P= 0.08). There was significant difference in the mean BC PTA between those who had procedure less than 1 hour; 37.2dB and those greater than 1 hour 38.4dB; (P=0.004). According to the Quincke needle sizes; the mean BC PTA among those who had 26G and 27G were 37.4dB and 38.1dB respectively (P=0.2). Conclusion: HL complicating SA is significant and associated with duration of procedure thus should be included in informed consent for medico-legal and ethical reasons and measures must be taken to avoid the leak of cerebrospinal fluid

Response to the meningococcal meningitis epidemic (MME) at Aminu Kano Teaching Hospital, Kano (2008-2009).

In December 2008 an outbreak of Meningococcal Meningitis swept across sub Saharan Africa with Nigeria, especially its northern states worst affected. The management of Aminu Kano Teaching Hospital constituted an Emergency Preparedness & Response (EPR) committee. Over the course of 18 weeks from 5 January 2009 to 15 May 2009, AKTH managed 222 cases of suspected meningitis with 14 deaths (case fatality rate [CFR] of 6.3%). Twenty three per cent (23%) were microbiologically proven as meningococcal meningitis while 9% were confirmed to be pneumococcal meningitis. Male to female ratio was 1:1 with most patients (81%) aged below 14 years. The epidemic peaked in weeks 10 and 13 with 38 admissions in the respective weeks. Meningococcemia with purpura fulminans, post meningitic immune complex cutaneous vasculitis and polyarthritis were observed. Control measures instituted included provision of free ceftriaxone, chemoprophylaxis to contacts, vaccines to staff/families, and creation of dedicated isolation wards. Clinical management guidelines were developed and hospital staffs were also enlightened. Lessons learnt included the difficulty of discriminating between nosocomial transmission and community clusters; relative increase in pneumococcal meningitis during the epidemic; unreliability of penicillin/chloramphenicol; the utility of internet for communication; and the inadequacy of vaccines to meet staff & public demand.

Hypoglycaemic and hypolipidaemic effect of aqueous leaf extract of Murraya koenigii in normal and alloxan-diabetic rats.

The hypoglycaemic effect of aqueous leaf extract of Murraya koenigii was studied in normal and alloxan-induced diabetic rats. The extract was administered orally at 100 mg/Kg, 150 mg/Kg and 200 mg/Kg bodyweight each to respective groups of animals (Groups I, II and III) for seven days. Group IV received normal saline and served as control for the normal rats. For the alloxan-induced diabetic rats, the same dosage pattern was administered to three groups of rats for seven days (Groups V, VI and VII) while group VIII which received normal saline served as control. At the various dose levels administered, the glucose lowering effect was more pronounced in the alloxan-diabetic rats than in control rats. When compared with chlorpropamide, the glucose lowering effect of aqueous extract of Murraya koenigii was significantly (p < 0.05) lower at the dose levels administered in both normal and alloxan-diabetic rats.

Deep temporalis fascia in tympanomastoid reconstruction.

Various techniques have been described in the reconstruction of mastoidectomy cavity in an attempt to minimize or control the problems of persistent postoperative otorrhoea. We report the efficacy of deep temporalis fascia and its pedicled flap in 34 cases. Retrospective study method was used. There were 34 cases, 19 males and 13 females, the age ranged between 5 and 64 years, mean of 28 years. The clinical pathology included mastoiditis which was common to all the patients, others are middle ear polyp in 7, mastoid abscess 6, meningitis 4, lateral sinus thrombosis 3 and cholesteatoma 2. Comorbidity factors included diabetes mellitus in 2, moderate anaemia in 3 and septicaemia in 7. The procedures comprised of 18 modified radical mastoidectomy (MRM) and 8 atticoantrostomy (AA) with lining of the resulting cavity and tympanoplasty using a pedicled temporalis fascia flap; and 8 cortical mastoidectomy (CM) and tympanoplasty using a graft. The success rate in terms of control of otorrhoea was 55% and there was no case of postoperative wound infection, an improvement compared to an earlier report. In addition there was a reduction in terms of postoperative hospital stay to an average of 9 days. We found the technique simple to learn and needing minimal equipment, hence relevant to otolaryngologic practice in a resource--poor environment. In addition the deep temporalis fascia is an autologous tissue with no risk of immune rejection. We recommend that mastoid reconstruction with the temporalis fascia becomes a routine in mastoidectomy so as to achieve control of chronic discharging ear, particularly in the sub-Saharan Africa where this is still predominant.