Enhanced Synaptic Inhibition in the Cerebellar Cortex of the Ataxic PMCA2−/− Knockout Mouse

Mice with genetic deletion of a calcium extrusion pump, the plasma membrane calcium ATPase isoform 2, PMCA2, exhibit overt cerebellar ataxia, but the cellular mechanisms are only partially understood. Here, we report an enhanced synaptic GABAergic inhibition within the molecular layer of cerebellar cortex slices from PMCA2 knockout (PMCA2^?/?) mice, a finding that could contribute to the observed ataxia. Purkinje neurons from PMCA2^?/? mice exhibited an increased frequency and amplitude of spontaneous inhibitory post-synaptic currents that was accompanied by an enhanced spontaneous firing frequency of molecular layer interneurons (both basket cells and stellate cells). The elevated inhibition was sufficient to reduce the frequency and regularity of spike firing by PMCA2^?/? Purkinje neurons. Acute pharmacological inhibition of PMCA recapitulated some of these features in wild-type mice indicating that the changes were in part a direct result of PMCA2 removal. However, additional compensatory mechanisms within the PMCA2^?/? mouse were also a major factor. Indeed, morphological studies revealed an abnormally large number of molecular layer interneurons (basket cells and stellate cells) and GABAergic synapses within the PMCA2^?/? cerebellar cortex. We conclude that loss of PMCA2 adversely influences the function and organisation of Purkinje neuron synaptic inhibition as a major contributory mechanism to the ataxic phenotype of the PMCA2^?/? mouse.     

Penile Incarceration with Metallic Foreign Bodies: Management and Review of Literature

Introduction

Penile strangulation from constricting metallic objects disorders is an uncommon urological emergency which requires prompt intervention to prevent complications. The treatment modalities are diverse and characterized by lack of consensus.

Material and Methods

Three cases with penile incarceration due to constricting metallic objects who presented to our department were included in this study. All 3 patients required different management options highlighting the diversity of clinical presentation and need for customization of treatment as per the clinical scenario.

Results

The 3 patients required different approach for treatment. First patient could be managed by degloving of penile skin while second patient required mechanical removal of the foreign body and debridement of local necrotic tissues. The third patient had to undergo excision of gangrenous penile skin and skin grafting.

Conclusion

The study emphasizes the diversity of clinical presentations and the need for employing different surgical techniques to achieve the desired results.Key Words: Penile strangulation, Constricting objects, Penile amputation     

Arthrodesis After Infected Revision TKA: Retrospective Comparison of Intramedullary Nailing and External Fixation

Background

Infection after revision total knee arthroplasty (TKA) for previous septic TKA can be a challenging problem to treat due to loss of bone stock and soft tissue integrity. In these cases, arthrodesis is a well-recognized salvage procedure.

Questions/Purposes

The aim of this retrospective study was to compare the results as described by a Visual Analogue Scale (VAS) and the Lequesne Algofunctional Score (LAS) of knee arthrodeses performed by using either an external fixator (EF) or an intramedullary nail (IM).

Methods

The study included 34 knee arthrodesis divided in two groups: first group included 12 patients treated with EF and the second group of 22 patients dealt with IM nail. Clinical and functional evaluation was performed using the VAS and the LAS. Full-length radiographs were used to verify limb length discrepancy.

Results

VAS and LAS results showed a substantial improvement relative to preoperative condition in both groups. However, the LAS was significantly better in the IM nail group. The mean leg length discrepancy was significantly greater (4.5 cm) in the first group than in the second one (0.8 cm). No recurrence of infection was observed in the EF group while there were three recurrent infections in the IM nail group.

Conclusion

Our study supported the existing literature and found that reinfection after revision TKA can be effectively treated with arthrodesis. In presence of massive bone loss, we recommend arthrodesis with IM nail used as an endoprosthesis, without bone-on-bone fusion, to produce a stable and painless knee, while preserving the limb length. Use of an IM nail allowed us to get a better functional result than EF.     

Simple and effective approach for the treatment of traumatic wounds in non‐diabetic patients: a prospective open study

Infection is one of the most important obstacles in the wound‐healing process. Conventional methods used for the treatment of wound infections have their own limitations and hence, are difficult to control. If infection is not addressed well in time, it will further increase morbidity and cost of treatment. An attempt was made to develop a simple and effective treatment modality by using citric acid as the sole antimicrobial agent to control bacterial infections of traumatic wounds. A total of 259 cases of traumatic wounds infected with a variety of bacteria were investigated for culture and susceptibility, and susceptibility to citric acid. Citric acid ointment (3%) was applied to traumatic wounds to determine its efficacy in their treatment of traumatic wounds. In a culture and susceptibility study, a total of 369 aerobic bacteria and 7 fungi were isolated, with Staphylococcus aureus (30·31%) being the most common isolate and ciprofloxacin (61·43%) being the most effective agent. All the isolates were found to be inhibited by citric acid in in vitro studies (minimum inhibitory concentration – 500–2500 µg/ml). Citric acid ointment was found effective in controlling infections. Out of 259 cases, 244 (around 95%) were healed completely in 5–25 applications of 3% citric acid. As citric acid has antibacterial activity and wound‐healing property; hence it is the best alternative for the treatment of traumatic wounds. Besides these properties, citric acid has no adverse effects and it is a good dressing agent.     

A polymorphism in the type one complement receptor (CR1) involves an additional cysteine within the C3b/C4b binding domain that inhibits ligand binding

The type one complement receptor (CR1) contains a variable number of binding domains for C3b and C4b, formed through a nearly identical set of repeating units known as short consensus repeats (SCRs). Each SCR contains four cysteines that, by forming two disulfide bonds, impart a conformation critical for function. In this study, we identified a CR1 single nucleotide polymorphism (1597C>T) that results in an additional cysteine (483R>C) in SCR 8 of the N-terminal C3b/C4b binding domain, and occurring sporadically in corresponding SCRs of other repeated C3b/C4b binding domains. The normal carrier frequency for 483-C was 6.3% in 175 African Americans, and 2.4% in 153 Caucasians. In expression constructs containing one C3b/C4b binding domain, the 483-C residue reduced binding to C3b, C3bi, and C4b by over 80% (each p<0.0001), versus the wildtype construct. Full-length CR1 from 483-C carriers also exhibited reduced binding to C3b and C4b, although the effect was influenced by the total number of binding domains present. Race-matched comparisons between SLE patients (86 African Americans, 228 Caucasians) and the normal cohort showed that 483-C carrier status alone is not a risk factor for SLE or lupus nephritis. The physiological role of this polymorphism remains to be determined.