Proposed guidelines for the management of nodding syndrome

Nodding Syndrome is a poorly understood neurologic disorder of unknown aetiology that affects children and adolescents in Africa. Recent studies have suggested that the head nods are due to atonic seizures and Nodding Syndrome may be classified as probably symptomatic generalised epilepsy. As part of the Ugandan Ministry of Health clinical management response, a multidisciplinary team developed a manual to guide the training of health workers with knowledge and skills to manage the patients. In the absence of a known cause, it was decided to offer symptomatic care. The objective is to relieve symptoms, offer primary and secondary prevention for disability and rehabilitation to improve function. Initial management focuses on the most urgent needs of the patient and the immediate family until ‘stability’ is achieved. The most important needs were considered as seizure control, management of behavioural and psychiatric difficulties, nursing care, nutritional and subsequently, physical and cognitive rehabilitation. This paper summarises the processes by which the proposed guidelines were developed and provides an outline of the specific treatments currently being provided for the patients.     

Comparison of periodontal open flap debridement versus closed debridement with Er,Cr:YSGG laser

Background

Traditional periodontal open flap debridement (OFD) results in reduced pocket depth (PD), clinical attachment loss (CAL), gingival recession (GR) and postoperative pain and discomfort. The quest to overcome these shortcomings has led to research into Er,Cr:YSGG laser assisted pocket therapy (ELAPT). This study was designed to compare the clinical outcomes of ELAPT versus OFD.

Methods

Fifteen patients with a PD of ≥5 mm and ≤8 mm at two sites were selected. Test sites (Group 1) were treated by ELAPT and the control (Group 2) by OFD. Clinical parameters were recorded at baseline, 3 and 6 months and included Plaque Index (PI), Gingival Index (GI), modified Sulcular Bleeding Index (mSBI), PD, CAL and GR.

Results

Both treatments produced a reduction in PI, GI, mSBI and PD, an increase in GR, and a gain in CAL at 3 and 6 months. The mean gain of CAL in Group 1 at 3 and 6 months (1.60 ± 0.78 and 1.80 ± 0.63) was similar (p > 0.05) to the value of Group 2 (1.93 ± 0.88 and 2.00 ± 0.54). GR increased significantly (p < 0.05) only in Group 2 at 3 and 6 months (1.80 ± 0.56 and 1.87 ± 0.64) compared to Group 1 (0.50 ± 0.68 and 0.60 ± 0.74).

Conclusions

ELAPT compared with OFD results in similar CAL gains with less GR and significant reductions in PD, GI and mSBI, and may be considered as an alternative to surgical therapy.     

Neuropathy-Inducing Effects of Eribulin Mesylate Versus Paclitaxel in Mice with Preexisting Neuropathy

Eribulin mesylate (E7389, INN:eribulin mesilate Halaven^®) is a non-taxane microtubule dynamics inhibitor currently in clinical use for advanced breast cancer. Other microtubule-targeting agents for breast cancer, including paclitaxel and ixabepilone, display a common treatment dose-limiting toxicity of peripheral neuropathy (PN). In an earlier study, we found eribulin mesylate had a lower propensity to induce PN in mice than either paclitaxel or ixabepilone. In the current study, we compared additional PN induced by paclitaxel versus eribulin mesylate when administered to mice with preexisting paclitaxel-induced PN. Initially, paclitaxel at 0.75 × its maximum tolerated dose (MTD; 22.5 mg/kg) was given on a Q2Dx3 regimen for 2 weeks. The second chemotherapy was 0.5 MTD eribulin mesylate (0.875 mg/kg) or paclitaxel (15 mg/kg) on a similar regimen, starting 2 weeks after the first. Initial paclitaxel treatment produced significant decreases in caudal nerve conduction velocity (NCV; averaging 19.5 ± 1 and 22.2 ± 1.3 %, p < 0.001) and amplitude (averaging 53.2 ± 2.6 and 72.4 ± 2.1 %, p < 0.001) versus vehicle when measured 24 h or 2 weeks after dosing cessation, respectively. Additional 0.5 MTD paclitaxel further reduced caudal NCV and amplitude relative to immediately before initiation of the second regimen (by 11 ± 2.1 and 59.2 ± 5 %, p < 0.01, respectively). In contrast, 0.5 MTD eribulin mesylate caused no further decrease in caudal NCV. In conclusion, unlike additional paclitaxel treatment, eribulin mesylate administered to mice with preexisting paclitaxel-induced PN had limited additional deleterious effects at 6 weeks. These preclinical data suggest that eribulin mesylate may have reduced tendency to exacerbate preexisting paclitaxel-induced PN in clinical settings.     

Primary motor cortex long‐term plasticity in multiple system atrophy

In humans, intermittent and continuous theta‐burst stimulation (iTBS and cTBS) elicit long‐term changes in motor‐evoked potentials (MEPs) reflecting long‐term potentiation (LTP)‐ and depression (LTD)‐like plasticity in the primary motor cortex (M1). In this study, we used TBS to investigate M1 plasticity in patients with MSA. We also assessed whether responses to TBS reflect M1 excitability as tested by short‐interval intracortical inhibition (SICI), intracortical facilitation (ICF), short‐interval intracortical facilitation (SICF), and the input/output curves. We studied 20 patients with MSA and 20 healthy subjects (HS). Patients were clinically evaluated with the Unified Multiple System Atrophy Rating Scale. The left M1 was conditioned with TBS. Twenty MEPs were recorded from the right first dorsal interosseous muscle before TBS and 5, 15, and 30 minutes thereafter. In a subgroup of 10 patients, we also tested MEPs elicited by SICI, ICF, SICF, and input/output curves, before TBS. Between‐group analysis of variance showed that at all time points after iTBS MEPs increased, whereas after cTBS they decreased only in HS. In both subgroups tested, patients with predominant parkinsonian and cerebellar features, iTBS and cTBS left MEPs unchanged. MSA patients had reduced SICI, but normal ICF, SICF, and input/output curves. No correlation was found between patients' clinical features and responses to TBS and M1 excitability variables. These findings suggest impaired M1 plasticity in MSA. © 2013 International Parkinson and Movement Disorder Society     

Coincidental diagnosis of tuberculous lymphadenitis: a case report

The aim of this case report was to present a case of multiple calcified tuberculous lymph nodes found on a panoramic radiograph coincidently diagnosed in an endodontic clinic. A detailed discussion on the differential diagnosis of similar such calcification found in the same region is also presented. A 14‐year‐old girl was referred to our department with the complaint of painless swelling in the left side of the lower jaw. Clinical and radiographical examinations were performed, leading to the initial diagnosis of chronic periapical abscess. The patient's medical history was re‐evaluated. Advanced imaging and excisional biopsy were performed in order to confirm the final diagnosis. Regarding the presenting signs and symptoms of bilateral carious mandibular molars, a periapical inflammatory process was considered in the provisional diagnosis. A thorough examination and investigations were suggestive of cervical tuberculous lymphadenitis (scrofula), and the patient underwent excision of the same. The clinician should consider the possibility of chronic granulomatous inflammatory lesions in the differential diagnosis of radiopaque lesions.     

Inhibition of centromere dynamics by eribulin (E7389) during mitotic metaphase

Eribulin (E7389), a synthetic analogue of halichondrin B in phase III clinical trials for breast cancer, binds to tubulin and microtubules. At low concentrations, it suppresses the growth phase of microtubule dynamic instability in interphase cells, arrests mitosis, and induces apoptosis, suggesting that suppression of spindle microtubule dynamics induces mitotic arrest. To further test this hypothesis, we measured the effects of eribulin on dynamics of centromeres and their attached kinetochore microtubules by time-lapse confocal microscopy in living mitotic U-2 OS human osteosarcoma cells. Green fluorescent protein-labeled centromere-binding protein B marked centromeres and kinetochore-microtubule plus-ends. In control cells, sister chromatid centromere pairs alternated under tension between increasing and decreasing separation (stretching and relaxing). Eribulin suppressed centromere dynamics at concentrations that arrest mitosis. At 60 nmol/L eribulin (2 x mitotic IC(50)), the relaxation rate was suppressed 21%, the time spent paused increased 67%, and dynamicity decreased 35% (but without reduction in mean centromere separation), indicating that eribulin decreased normal microtubule-dependent spindle tension at the kinetochores, preventing the signal for mitotic checkpoint passage. We also examined a more potent, but in tumors less efficacious antiproliferative halichondrin derivative, ER-076349. At 2 x IC(50) (4 nmol/L), mitotic arrest also occurred in concert with suppressed centromere dynamics. Although media IC(50) values differed 15-fold between the two compounds, the intracellular concentrations were similar, indicating more extensive relative uptake of ER-076349 into cells compared with eribulin. The strong correlation between suppression of kinetochore-microtubule dynamics and mitotic arrest indicates that the primary mechanism by which eribulin blocks mitosis is suppression of spindle microtubule dynamics.     

Hydrocelectomy under local anaesthesia in a Nigerian adult population

Background

Hydrocele is abnormal collection of serous fluid in the tunica vaginalis or a patent processus vaginalis. It is commonly encountered in our practice and often requires surgical treatment. However in our setting and in many underdeveloped countries, availability of general anaesthetic service is poor due to lack of trained personnel and equipment.

Objectives

To ascertain the practicability and acceptability of hydrocelectomy under sedation and local anaesthesia in Nigerian adults with hydrocele

Patients and Methods

A prospective study was carried out over a two year period on patients that had hydrocelectomy at the surgery unit of the Obafemi Awolowo University Teaching Hospitals Complex, Wesley Guild Hospital, Ilesa. Consecutive patients with diagnosis of hydrocele who consented had hydrocelectomy using intramuscular diazepam sedation and spermatic-cord block with 0.5% plane xylocaine and the scrotum infiltrated with same along the line of incision.

Results

Fifty adult patients were studied: age range 15–94 years. Eighty percent of the patients had unilateral hydrocele and the commonest type was vaginal hydrocele (94%). All patients had hydrocelectomy, 96% were under local anaesthesia while 4% were converted to general anaesthesia. All patients except one prefer to have future surgery under such local anaesthesia and sedation.

Conclusion

Hydrocelectomy under local anaesthesia and sedation is practicable and was tolerated and accepted by the adults patients studied.     

Sexual orientation and substance use trajectories in emerging adulthood

Aims The current study examined developmental changes in substance use behaviors (SUBS) based upon sexual orientation. The analyses also attempted to address a number of methodological limitations in the extant longitudinal literature (i.e. distinct operationalizations of sexual orientation, timing of sexual orientation assessment with respect to reports of SUBs, non‐linear growth). Participants Data were drawn from a longitudinal study of incoming first‐time college students at a large public university (n = 3720). Design After a paper‐and‐pencil assessment just prior to matriculation, participants completed a web‐based survey every fall and spring for 4 years (sub‐sample n = 2854). Findings Latent growth models revealed that sexual minorities demonstrated significant heterogeneity with regard to substance use trajectories. Initial levels and trajectories of the frequency of substance use for sexual minority individuals were distinct, generally, from their exclusively heterosexual peers. Methodologically, the timing of the assessment of sexual orientation influenced the results, and modeling non‐linear components indicated that sexual minorities are at risk for exponential increases in their frequency of certain SUBs over time (i.e. drunkenness; cannabis use). Conclusions Sexual minority and majority individuals exhibited differences in SUBs during emerging adulthood, especially when using self‐identification to define sexual orientation. Individuals who endorsed a sexual minority self‐identification at the onset of emerging adulthood, as opposed to 4 years later, evidenced exponential increases in rates of drunkenness and cannabis use. These results support that the timing of assessment is important and that some trajectories of sexual minority SUBs are non‐linear during this developmental period.