Schwann cells seeded in acellular nerve grafts improve functional recovery

Introduction: This study evaluated whether Schwann cells (SCs) from different nerve sources transplanted into cold‐preserved acellular nerve grafts (CP‐ANGs) would improve functional regeneration compared with nerve isografts. Methods: SCs isolated and expanded from motor and sensory branches of rat femoral and sciatic nerves were seeded into 14mm CP‐ANGs. Growth factor expression, axonal regeneration, and functional recovery were evaluated in a 14‐mm rat sciatic injury model and compared with isografts. Results: At 14 days, motor or sensory‐derived SCs increased expression of growth factors in CP‐ANGs versus isografts. After 42 days, histomorphometric analysis found CP‐ANGs with SCs and isografts had similar numbers of regenerating nerve fibers. At 84 days, muscle force generation was similar for CP‐ANGs with SCs and isografts. SC source did not affect nerve fiber counts or muscle force generation. Conclusions: SCs transplanted into CP‐ANGs increase functional regeneration to isograft levels; however SC nerve source did not have an effect. Muscle Nerve 49 : 267–276, 2014     

Peripheral Quantitative Computed Tomography: Optimization of Reproducibility Measures of Bone Density, Geometry, and Strength at the Radius and Tibia

The aim of this study was to determine the reproducibility for in vivo measurements at the radius and tibia for trabecular and cortical parameters, bone geometry, and bone strength indices with the peripheral quantitative computed tomography (pQCT) XCT 3000. We performed 3 repeated scans within 2 mo at the radius (N = 18) and tibia (N = 16) on healthy, premenopausal women, aged 22–35 yrs and report precision measures including %coefficient of variation (%CV) and least significant changes (LSCs). For the radius, we studied 2 sections (4% and 33% of total length) and for the tibia, 3 sections (4%, 38%, and 66% of total length). Reproducibility for radius at 33% and tibia at every site was good (%CV ranged from 0.02% to 2.19%). The precision error for the distal 4% radius was, however, higher. The reproducibility at the distal radius improved when we considered only the scans with a change of ±10 mm² in the radius total area at this site (%CV from 0.87% to 2.25%). This study showed that, when follow-up measurements are carefully obtained, pQCT yields excellent reproducibility at both the radius and tibia. These precision errors, in conjunction with changes in LSC for the pQCT measures, are useful for research and potential clinical applications.     

Pharmacokinetics of colistin in critically ill patients with multidrug-resistant Gram-negative bacilli infection

Purpose

Colistin, which had not been used widely because of nephrotoxicity and neurotoxicity, has gained clinical importance in recent times due to the resurgence of multidrug-resistant Gram-negative bacilli. Very few studies, especially pharmacokinetic studies, have been performed with intravenous colistimethate sodium, and none in India. The aim of our study was to study the single-dose and steady-state pharmacokinetics of colistin in patients with multidrug-resistant Gram-negative bacilli infections.

Method

This was a prospective open-label pharmacokinetic study done in an intensive care unit in a tertiary care hospital on 15 critically ill patients with proven multidrug-resistant Gram-negative bacilli infection. Colistimethate sodium was injected as intermittent intravenous infusions in accordance with the recommendations on the package insert. For patients weighing ≥60 kg with a normal renal function or with a creatinine clearance (CL_CR) of between 20 and 50 ml/min, the drug was administered at 2 million international units (MIU) every 8 h; for those with a CL_CR of 10–20 ml/min, the dose was 2 MIU every 12 h. Those patients who weighed <60 kg were administered 50,000 IU/kg/day in three divided doses at 8-h intervals. Both single-dose and steady-state pharmacokinetics of colistin were determined and correlated with clinical outcomes.

Results

A wide inter-individual variation was observed in pharmacokinetic parameters. The median (range) of the maximum plasma drug concentration/minimum inhibitory concentration (C_max/MIC) ratio for Acinetobacter spp. was 13.4 (1.3–40.3) following the administration of a single dose of colistimethate sodium and 26.3 (0.9–64.9) at steady-state. For Pseudomonas spp., these values were 3.18 (1.6–23.1) following the single dose and 3.82 (2.3–10.9) at steady-state. For those patients whose cultures grew Acinetobacter spp., an optimum value of the C_max/MIC ratio of >8 was achieved in seven of nine patients after the single dose and in seven of eight patients at steady-state. For those patients whose cultures grew Pseudomonas spp, only one patient after the single dose and one patient at steady-state achieved a C_max/MIC ratio of >8. A significant association was noted between dose and survival, and a trend was observed with patients weighing ≤60 kg (who received 50,000 IU/kg/day instead of 6 MIU/day for those >60 kg) having an increased mortality.

Conclusion

The pharmacokinetic parameters of colistin were comparable to those reported in previous studies in critically ill patients. However, the recommended dose may be inadequate to maintain the C_max/MIC ratio to an optimal level—at least in patients infected with Pseudomonas spp. The dose recommendation should be based only on creatinine clearance and not body weight.

     

Ten-year outcomes of a one-stop colposcopy clinic: a unique service for low grade cytology

Objective

To determine patient acceptance of treatment, and treatment default rate, at a one-stop clinic, and to establish the concordance of punch and loop histology for high grade cervical intraepithelial neoplasia (CIN) by date of excisional treatment.

Study design

Retrospective review of computerised data and clinic files of 2090 women with low grade cytology undergoing cervical punch biopsies between 2001 and 2011 at the colposcopy clinic, Northern Gynaecological Oncology Centre, Gateshead, UK. Punch biopsies were micro-wave processed and reported within 2 h, and women were offered immediate loop biopsy if high grade CIN was confirmed. Data were collected regarding patients’ choice for immediate or deferred treatment and default rate. Histological outcomes were compared between those undergoing immediate and deferred loop biopsies.

Results

Of the 360 women (17%) with high grade CIN on punch biopsy, 259 (72%) opted to have immediate loop treatment at the first visit. Of these women, 190 (73%) had high grade CIN on loop histology. Of 97 women (27%) who had deferred loop biopsy after a median of 28 days (range 7–112), 65 (67%) had high grade CIN on loop histology. The default rate at return for treatment appointments was 0% amongst all patients.

Conclusion

This one-stop colposcopy clinic reduces defaulting from treatment. It has proven to be a sustainable service and the majority of women, when given the choice, opt for immediate loop treatment at their first visit.     

Anticonvulsant hypersensitivity syndrome to lamotrigine confirmed by lymphocyte stimulation in vitro

Anticonvulsant hypersensitivity syndrome (AHS) developing to lamotrigine, a non-aromatic anticonvulsant, has rarely been reported. We present a two-year-old boy with refractory epilepsy on valproic acid and lamotrigine therapy who developed fever and a maculopapular itchy rash. Blood investigations detected lymphocytosis and thrombocytopenia. With a presumptive diagnosis of AHS, lamotrigine was discontinued. The fever and rash resolved over the next three days and the child was discharged on valproic acid and clobazam. The diagnosis was confirmed by in vitro lymphocyte toxicity assay, which not only demonstrated increased cell death following exposure to lamotrigine, but also to the three first-line aromatic anticonvulsants: phenytoin, phenobarbital and carbamazepine. The potential of first-line aromatic anticonvulsants to cause AHS should be remembered in a patient who has developed AHS on exposure to lamotrigine. Timely recognition of this rare but potentially fatal drug reaction is important.