Somatostatin for Uveitic Cystoid Macular Edema (CME)

Purpose: To report the favorable response of bilateral recalcitrant uveitic cystoid macular edema (CME) to treatment with a somatostatin analog. Methods: Medical ophthalmic history and the results of ophthalmic examinations were recorded. Fluorescein angiography (FA) studies were reviewed. Results: A 52-year-old white female with intermediate uveitis developed bilateral recalcitrant CME. Treatment with subcutaneous injections of the somatostatin analog octreotide resulted in partial resolution of the CME and improvement of visual acuity. Conclusions: Somatostatin may play a role in the treatment of CME secondary to uveitis.     

Multiple paths to a drug resistance phenotype: mutations, translocations, deletions and amplification of coding genes or promoter regions, epigenetic changes and microRNAs.

The remarkable responses observed with imatinib (Gleevec) in the therapy of CML led many scientists to think that drug resistance, long recognized as a problem with "cytotoxic" agents, would soon become a thing of the past. But then reality set in. We learned that imatinib, a wonderful drug by any measure, was also susceptible to the development of resistance, as was gefitinib (Iressa), and then erlotinib (Tarceva). This evidence on resistance to "novel agents" together with new data on the complexity of cancer, the rapidly evolving story of microRNAs and their diverse roles, as well as evidence of the importance of epigenetic changes have allowed us to refine our models of drug resistance and how cells acquire these phenotypes. In this overview I will look at examples of how drug resistance develops including older and more recent data on the role of mutations, translocations, deletions, and amplification. The role of epigenetic changes and microRNAs will be discussed, as examples of different mechanisms by which a cell achieves the same end. Recurrent themes that have emerged will be underscored as we seek to understand how drug resistance occurs.     

Use of microvascular free flaps in the reconstruction of the anterior and middle skull base

Different reconstruction techniques of the anterior and middle skull base as consequence of a defect after surgical treatment of neoplastic pathologies are described in the literature. The aim of the present study is to present our experience regarding the use of microvascular free flaps for reconstruction of the anterior or middle skull base after large defects caused by removal of malignant neoplasms. From 2000 to 2004, in the Department of Maxillo-Facial Surgery of the University of Rome "La Sapienza" and "Tor Vergata," 13 surgical procedures for reconstruction of anterior and middle skull base defects by free flaps were performed in 11 patients. Data on patient demographics, histopathology, location and size of defect, type of reconstruction, and postoperative complications were obtained from medical record charts. A safe soft tissue closure of the intracranial space was achieved in all patients. Defect repair was accomplished by revascularized transfer of rectus abdominis flaps in seven cases, latissimus dorsi muscle flaps in two patients, radial forearm flap in one case, and fibula flap in one case. There were two total flap losses; the secondary defect repair was accomplished in both cases by revascularized transfer of latissimus dorsi muscle flap. No donor site complications were observed in all the flaps. The mean operation time was 85 hours; patients were hospitalized for a mean period of 14 days. The method of choice for the reconstruction of anterior or middle skull base defect should be based upon careful evaluation of the single case and, particularly, the localization and entity of the residual defect. For defects that require large amounts of soft tissue, the latissimus dorsi free flap and the rectus abdominis free flap are the best appropriate choices for reconstructive procedures for anterior and middle skull base tumors.     

Asking the community about cutpoints used to describe mild, moderate, and severe pain.

Clinical practice guidelines recommend that numeric rating scales be used to document the severity of perceived pain, yet patients and clinicians often opt to use simpler classification systems such as mild, moderate, or severe. To assess how well the numeric scales correlate with the tri-level classification system for describing pain severity, we conducted a subanalysis of a larger population-based study of pain management preferences. Our primary objective was to identify the numeric boundaries used by 287 adults to describe pain as mild, moderate, or severe. We examined differences in the means of the upper and lower limits for mild, moderate, and severe pain according to demographic characteristics and type of pain. Ranges reported for each pain level were 1.3 to 3.6 (mild), 4.3 to 6.5 (moderate), and 7.5 to 9.8 (severe). The primary finding was that "healthy" community adults rated the pain severity cutpoints much as patients with clinical pain did, 1 to 4 for mild, 5 to 6 for moderate, and 7 to 10 for severe. These results suggest that numeric rating scales can be used in clinical practice with both patients and community-dwelling adults. Our findings also support encouraging the general public to use a 0 to 10 scale to rate their pain intensity. PERSPECTIVE: Methods used to describe numeric cutpoints for mild, moderate, and severe pain were applied to community adults. Having standard categories to describe pain severity might increase clinicians' confidence in using a numeric scale to make treatment decisions. Further studies of cutpoint methodology and its clinical importance are warranted.     

Cytogenetic response to imatinib treatment in Southern Brazilian patients with chronic myelogenous leukemia and variant Philadelphia chromosome

Variant Philadelphia (Ph) chromosome can be observed in 5–10 % of chronic myelogenous leukemia (CML) patients. However, there are only a few studies which have analyzed the prognostic implications of these complex translocations in CML patients after the advent of imatinib mesylate and the results found are conflicting. We investigated the clinical features and cytogenetic response of Brazilian chronic phase (CP) CML patients with variant Ph treated with imatinib mesylate. Among 93 CP CML patients, eight (8.6 %) exhibited complex translocations, involving one (n?=?6), two (n?=?1), or three (n?=?1) additional chromosomes. At 6, 12, and 18 months, a complete cytogenetic response was observed in 100 % of variant Ph patients, respectively. No significant difference was found between variant Ph and standard translocation patients regarding the response to IM treatment at 6, 12, and 18 months. Likewise, there was no statistically significant difference between the two groups concerning the overall survival, failure-free survival, progression-free survival, and event-free survival. The results obtained in our study, despite our sample size, suggest, in agreement to other data found in the literature, that the presence of variant Philadelphia chromosome does not bestow a prognostic disadvantage when compared to the group with classic Ph. This observation does not suggest the need to adjust the treatment protocol due to the presence of variant Ph. However, further studies with larger sample sizes and evaluating both the cytogenetic and molecular response to IM treatment should be conducted to confirm our findings.     

Cough reflex responses during pulmonary C-fibre receptor activation in anesthetized rabbits

We investigated the changes induced by pulmonary C-fibre receptor activation in the cough reflex evoked by mechanical stimulation of the tracheobronchial tree in pentobarbitone anesthetized, spontaneously breathing rabbits. Phrenic nerve and abdominal muscle activities were monitored along with tracheal and arterial blood pressures. The activation of pulmonary C-fibre receptors by means of right atrial injection of phenylbiguanide (PBG) caused the pulmonary chemoreflex characterized by tachypnea, bradycardia and hypotension. During the pulmonary chemoreflex, the time components (total cycle duration, inspiratory and expiratory times) of the cough motor pattern significantly decreased, whereas no consistent changes in peak phrenic and abdominal activity, peak tracheal pressure and number of coughs evoked by each stimulation trial were observed. At variance with previous findings in cats and dogs, the results show that tracheobronchial cough is not significantly reduced in the rabbit during PBG-induced chemoreflex. This study is the first to provide evidence supporting the hypothesis that the time components of the cough motor pattern are, to some extent, dependent upon the timing characteristics of the ongoing respiratory activity and suggests a novel mechanism leading to cough depression.     

Evaluation of obstructive sleep apnea in pediatric patients with facio-craniostenosis: a brief communication

Purpose

This study aimed to evaluate our experience in treating cranio-maxillo-mandibular malformations with hypoplasia of the upper and middle third of the face. We wished to determine a new diagnostic path involving a new clinical questionnaire for obstructive sleep apnea (OSA) evaluation, which we have developed by merging existing tests, literature findings, and our clinical experience to obtain a high level of information with minimal cost. This questionnaire is an improvement of the other anamnestic tests in the literature.

Methods

The study was carried out on 17 pediatric patients affected by syndromic craniofacial malformations and treated with surgical advancement of the middle third of the face, associated with or without upper third advancement, through osteodistraction. We used the obstructive airway child test (OACT) for clinical evaluation. The OACT is an OSA assessment test based on questions proposed to the patient’s relatives. All patients underwent polysomnography for instrumental assessment of OSA. These patients were also required to have a computed tomography scan for surgical planning. At the start of the treatment, 11 patients had severe OSA, 4 patients had moderate OSA, and 2 patients had slight OSA.

Results

At the end of the treatment, 6 patients had slight OSA and 11 patients had no OSA; these data were confirmed with OACT and polysomnography.

Conclusions

Based on our results, we suggest the following flowchart: OACT for OSA clinical evaluation; CT scan for evaluation of the volume of the rhinoropharyngeal air column, anatomical obstruction detection, and surgical planning; and polysomnography for diagnostic confirmation.     

When Surgical Resources are Severely Constrained,Who Receives Care? Determinants of Access to Orthopaedic Trauma Surgery in Uganda

Background

In low- and middle-income countries, the volume of traumatic injuries requiring orthopaedic intervention routinely exceeds the capacity of available surgical resources. The objective of this study was to identify predictors of surgical care for lower extremity fracture patients at a high-demand, resource-limited public hospital in Uganda.

Methods

Skeletally mature patients admitted with the intention of definitive surgical treatment of an isolated tibia or femur fractures to the national referral hospital in Uganda were recruited to participate in this study. Demographic, socioeconomic, and clinical data were collected through participant interviews at the time of injury and 6 months post-injury. Social capital (use of social networks to gain access to surgery), financial leveraging, and ethnicity were also included as variables in this analysis. A probit estimation model was used to identify independent and interactive predictors of surgical treatment.

Results

Of the 64 patients included in the final analysis, the majority of participants were male (83%), with a mean age of 40.6, and were injured in a motor vehicle accident (77%). Due to resource constraints, only 58% of participants received surgical care. The use of social capital and femur fractures were identified as significant predictors of receiving surgical treatment, with social capital emerging as the strongest predictor of access to surgery (p < 0.05).

Conclusion

Limited infrastructure, trained personnel, and surgical supplies rations access to surgical care. In this environment, participants with advantageous social connections were able to self-advocate for surgery where demand for these services greatly exceeded available resources.