Unfavourable results in the repair of the cleft lip

Introduction:

Unfavorable results in unilateral and bilateral cleft lip repair are often easy to spot but not always easy to prevent as to treat. We have tried to deal with the more common problems and explain possible causes and the best possible management options from our experience.

Unilateral cleft lip repair:

Unfavorable results immediately after repair involve Dehiscence and Scaring. Delayed blemishes include vermillion notching, a short lip, deficiency in the height of the lateral vermillion on the cleft side, white roll malalignment, oro-vestibular fistula, the cleft lip nose deformity, a narrow nostril and a “high-riding” nostril. We analyze the causes of these blemishes and outline our views regarding the treatment of these.

Bilateral cleft lip:

Immediate problems again include dehiscence as also loss of prolabium or premaxilla. Delayed unfavorable results are central vermillion deficiency, a lip that is too tight, bilateral cleft lip nose deformity, problems with the premaxilla and maxillary growth disturbances. Here again we discuss the causation of these problems and our preferred methods of treatment.

Conclusion:

We have detailed the significant unfavorable results after unilateral and bilateral cleft lip surgery. The methods of treatment advocated have been layer from our own experience.KEY WORDS: Cleft lip nose, contractures, high riding nostrils, scarring, unfavourable results, vermillion deficiency     

Neuroprotection with glatiramer acetate: evidence from the PreCISe trial

The phase III, multicenter, randomized, placebo-controlled PreCISe trial assessed glatiramer acetate (GA) effects in patients with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS). To assess the neuroprotective effect of GA in a subset of patients in the PreCISe trial, we used proton magnetic resonance spectroscopy (MRS) to measure N-acetylaspartate (NAA), a marker of neuronal integrity, in a large central volume of brain. Thirty-four CIS patients randomized to GA 20 mg/day (n = 19) SC or placebo (n = 15) were included. Patients who relapsed (developed clinically definite MS [CDMS]) were removed from the substudy. NAA/creatine (NAA/Cr) ratios were compared between GA-treated and placebo-treated patients. Twenty patients with CIS had not converted to CDMS and were still in the double-blind phase of the trial at 12 months of follow-up. Paired changes in NAA/Cr differed significantly in patients treated with GA (+0.14, n = 11) compared with patients receiving placebo (?0.33, n = 9, p = 0.03) at 12 months, consistent with a neuroprotective effect of GA in vivo. Patients with CIS who received GA showed improvement in brain neuroaxonal integrity, as indicated by increased NAA/Cr, relative to comparable patients treated with placebo, who showed a decline in NAA/Cr consistent with findings from natural history studies.     

Interesting case of narrow QRS tachycardia. What is the mechanism?

A 67‐year‐old female presented with history of recurrent palpitations. During one of the episodes of palpitation, a narrow QRS tachycardia was recorded and it was reported to be terminated with intravenous adenosine. The 12‐lead electrocardiogram (ECG) showed no manifest ventricular preexcitation. ECG was within normal limits. The patient underwent an electrophysiology study after informed consent. She was taking calcium channel blockers and that was stopped five half‐lives prior to the procedure. As catheters were being placed, a narrow QRS tachycardia got induced. During the study, there was development of right bundle branch block during the tachycardia. What is the mechanism of the tachycardia?     

Disseminated Fusarium oxysporum neurospinal infection

We report a case of disseminated meningospondylodiscitis in an elderly diabetic patient caused by Fusarium oxysporum. As the clinical presentation was nonspecific, the diagnosis of the condition could only be arrived at after laboratory and imaging studies. The diagnosis of the condition requires a high index of suspicion. Patient underwent thorough surgical debridement along with a short course of variconazole and remained asymptomatic after 36 months of diagnosis. Fusarium is a large genus of filamentous fungi widely distributed in soil and in association with plants. It is known to cause local infections (nail, cornea) in healthy humans and disseminated infection only in the immunocompromised.     

Homeostasis of functional maps in active dendrites emerges in the absence of individual channelostasis

The maintenance of ion channel homeostasis, or channelostasis, is a complex puzzle in neurons with extensive dendritic arborization, encompassing a combinatorial diversity of proteins that encode these channels and their auxiliary subunits, their localization profiles, and associated signaling machinery. Despite this, neurons exhibit amazingly stereotypic, topographically continuous maps of several functional properties along their active dendritic arbor. Here, we asked whether the membrane composition of neurons, at the level of individual ion channels, is constrained by this structural requirement of sustaining several functional maps along the same topograph. We performed global sensitivity analysis on morphologically realistic conductance-based models of hippocampal pyramidal neurons that coexpressed six well-characterized functional maps along their trunk. We generated randomized models by varying 32 underlying parameters and constrained these models with quantitative experimental measurements from the soma and dendrites of hippocampal pyramidal neurons. Analyzing valid models that satisfied experimental constraints on all six functional maps, we found topographically analogous functional maps to emerge from disparate model parameters with weak pairwise correlations between parameters. Finally, we derived a methodology to assess the contribution of individual channel conductances to the various functional measurements, using virtual knockout simulations on the valid model population. We found that the virtual knockout of individual channels resulted in variable, measurement- and location-specific impacts across the population. Our results suggest collective channelostasis as a mechanism behind the robust emergence of analogous functional maps and have significant ramifications for the localization and targeting of ion channels and enzymes that regulate neural coding and homeostasis.Channel homeostasis, or channelostasis, refers to the regulation of the density, kinetics, voltage dependence, binding interactions, and the subcellular localization of individual ion channel types within a given cell [compared to proteostasis (1)]. Hippocampal CA1 pyramidal neurons are endowed with complex dendritic morphology and express numerous voltage-gated ion channels (VGICs), which govern critical neuronal functions across their somatodendritic arbor (2–6). Channelostasis in such neurons is an exceptionally complex puzzle, given the enormous morphological and molecular complexities accompanied by a myriad of subcellular channel localization profiles, resulting in an immense combinatorial diversity in channel expression profiles (4, 7–11). A further conundrum that compounds this complex puzzle is that neurons, despite these underlying complexities, exhibit amazingly regular gradients in several functional properties that manifest as maps along a continuous neuronal topograph (3). The coexistence of all these topographically continuous maps along the same neuronal topograph is mediated by intricately regulated subcellular localization of various VGICs.In this study, we asked whether the topographically connected structure of a complex dendritic arbor, constrained to sustain these continuous functional maps, imposes rules on the individual and collective channelostasis of underlying ion channels. Specifically, the sustenance of the coexistent functional maps has to account for observations that several VGICs govern and modulate any given functional property within a single neuron (12–15) and that there are spatially widespread, distance-dependent influences of ionic conductances across the dendritic arbor (16, 17). Do these requirements impose constraints on the expression profiles and properties of somatodendritic ion channels, if several functional maps were to be coexistent and continuous on the same neuronal topograph? Do spatial and kinetic interactions among channel gradients across the neuronal topograph facilitate or hamper robustness of the several functional maps? Does the connected dendritic structure impose strong pairwise correlations on the expression profiles of different channels that mediate the coexistence of these functional maps? What are the location-dependent contributions of different channels to the several functional maps expressed by hippocampal neurons?We addressed these questions by using the powerful global sensitivity analysis methodology on morphologically realistic neuronal models and dissected six functional maps with reference to 32 passive and active parameters that governed the neuron’s somatodendritic properties. We used detailed quantitative experimental measurements of channel distributions and of physiological properties from the soma and dendrites of CA1 pyramidal neurons to resolve the validity of 20,420 models generated by randomly assigning values for these 32 parameters. We found that disparate model parameters resulted in topographically analogous populations of these valid neuronal models with weak pairwise correlations between parameters, implying collective, and not individual/pairwise channelostasis as a mechanism behind homeostasis in functional maps. Finally, we derived a methodology, within the global sensitivity analysis framework, to assess the relative contribution of the different channel conductances to the various functional measurements, using virtual knockout simulations on the valid model population. Results from our study suggest that neural mechanisms involved in regulating functional homeostasis of topographically continuous maps need not maintain the density and properties of individual channels at fixed values at specific locations.