Bone graft gel: autologous growth factors used with autograft bone for lumbar spine fusions

A method to combine autologous growth factors (AGF) with autologous bone graft in a bone graft gel for spine fusions is described. The bone graft gel can be inserted into cages for interbody fusions or used directly for posterolateral intertransverse fusions. Sixty patients have undergone spinal fusion surgery under this technique. No equipment problems have been encountered and no adverse effects observed that could be attributed to AGF. Early clinical outcomes indicated solid or maturing fusions in 58 of 60 patients. AGFs to enhance bone healing represent an economical and readily available autologous source of growth factors.     

Cardiopulmonary function of cats with respiratory distress induced by N-nitroso N-methylurethane

The purposes of this study were to determine the effects of positive end-expiratory pressure (PEEP) and end-expiratory lung volume on systemic blood flow, whether PEEP levels yielding maximum systemic oxygen transport are associated with maximum lung compliance, and the effects of end-expiratory lung volume on pulmonary resistance to gas flow, in an animal model of respiratory distress. Twelve cats were inoculated with 12 mg/kg N-Nitroso N-Methylurethane (NNNMU) to induce respiratory distress. The NNNMU caused a 76% decrease in disaturated phosphatidyl-choline of lung lavage, a 34% decrease in functional residual capacity (FRC), an 80% decrease in lung compliance, an 88% increase in pulmonary resistance to gas flow, a 43% decrease in PaO2, and a 37% decrease in oxygen consumption. Systemic blood flow and systemic oxygen transport were not significantly altered by the chemically induced respiratory distress. PEEP levels of 5.1 +/- 0.8 cm H2O returned end-expiratory lung volume to normal FRC levels. Increases in PEEP caused systemic blood flow to decrease even when end-expiratory lung volume was below or equal to normal FRC levels but did not significantly affect systemic oxygen transport, lung compliance, or pulmonary resistance. We conclude that in cats with NNNMU-induced respiratory distress: PEEP causes decreases in systemic blood flow, lung compliance and systemic oxygen transport are not clear indicators of optimal PEEP level, and returning end-expiratory lung volume to normal FRC does not significantly reduce pulmonary resistance to gas flow.     

Allosteric modulation of the muscarinic M4 receptor as an approach to treating schizophrenia

Current antipsychotics provide symptomatic relief for patients suffering from schizophrenia and related psychoses; however, their effectiveness is variable and many patients discontinue treatment due to side effects. Although the etiology of schizophrenia is still unclear, a leading hypothesis implicates an imbalanced dopaminergic system. Muscarinic acetylcholine (ACh) receptors regulate dopamine levels in key areas of the brain involved in psychosis, with the M(4) subtype emerging as a key regulator of dopaminergic hyperactivity. Unfortunately, no selective small molecule tools exist to provide pharmacological validation of this hypothesis. Here, we describe the discovery of a small molecule modulator, LY2033298, that is highly selective for human M(4) receptors by virtue of targeting an allosteric site on this receptor. Pharmacological assays confirmed the selectivity of LY2033298 for the M(4) receptor and revealed the highest degree of positive allosteric enhancement of ACh potency thus far identified. Radioligand binding assays also show this compound to directly potentiate agonist binding while having minimal effects on antagonist binding. Mutational analysis identified a key amino acid (D(432)) in the third extracellular loop of the human M(4) receptor to be critical for selectivity and agonist potentiation by LY2033298. Importantly, LY2033298 was active in animal models predictive of clinical antipsychotic drug efficacy indicating its potential use as a first-in-class, selective, allosteric muscarinic antipsychotic agent.     

The Evaluation of Efficacy of Post-Operative Antibiotics in the Open Reduction of the Zygomatic and Mandibular Fracture: A Prospective Trial

Introduction

The administration of pre and post-operative antibiotics for open reduction and internal fixation of facial fracture is the usual norm followed. Although the benefit of antibiotic has been established in the literature, the value of post-operative administration has been questioned and yet not extensively studied or investigated. There are rising concerns over the duration and undesired effects of antibiotics. The purpose of the study was to evaluate necessity and/or efficacy of post-operative antibiotics in the open reduction of zygomatic and mandibular fracture.

Methods

Sixty patients who underwent open reduction and internal fixation were divided into two groups for the trial. Ab group (30 patients) received pre, intra and post-operative antibiotics. Non-Ab group (30 patients) did not receive post-operative antibiotics though pre and intra-operative antibiotics were administered. Patients were evaluated for post-op infection at the end of 1st and 3rd week after operation.

Results

Among 60 patients, 2 patients (1 from Ab group and 1 from non-Ab group) were infected; so statistically no significant difference in result was obtained (Fisher’s exact test, P value = 1).

Conclusion

In this trial, the use of post-operative antibiotics in the open reduction and internal fixation of facial fracture was shown to confer no benefit/efficacy in reducing the chances of infection.     

Follicular lesion of undetermined significance in thyroid FNA revisited

Controversy exists regarding the validity of follicular lesion of undetermined significance (FLUS), an indeterminate diagnostic category of The Bethesda System for Reporting Thyroid Cytopathology (BSRTC). According to BSRTC, FLUS carries a 5–15% risk of cancer. This study was designed to determine if cytomorphology could stratify FLUS into subgroups with different risks of malignancy. Reports of 127 consecutive FNAs reported as FLUS with subsequent tissue diagnoses were evaluated for the presence of various cytologic features and the results were correlated with histological diagnoses. FLUS cases with focal nuclear atypia (nuclear overlap/crowding, nuclear grooves/membrane irregularities, nuclear enlargement, and/or nuclear pseudoinclusions) were more frequently malignant on excision whereas those with architectural atypia (microfollicles) were more often benign on excision (P < 0.05). The presence of any one or more of these nuclear features increased the risk of carcinoma in subsequent thyroid resection. Papillary carcinomas predominated in excised FLUS cases with focal nuclear atypia whereas most FLUS with architectural atypia were adenomas or hyperplastic nodules on histological evaluation. BSRTC recommends that thyroid aspirates containing follicular cell nuclear and/or architectural atypia insufficient for a diagnosis of suspicious for follicular neoplasm, suspicious for malignancy or malignant be classified as FLUS. Our findings indicate that FLUS cases with focal nuclear atypia carry a risk for malignancy that is substantially higher than that assigned to FLUS and are best classified as suspicious. FLUS cases lacking these atypical nuclear features have a risk for malignancy that approximates the risk BSRTC has assigned to FLUS. Diagn. Cytopathol. 2014;42:18–22. © 2013 Wiley Periodicals, Inc.